[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"anatomic-stage-iv-breast-cancer-ajcc-v8\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:anatomic-stage-iv-breast-cancer-ajcc-v8":28},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,49,0,25,[9,54,175,201,222,243,264,285,306,341,361,382,400,424,445,467,505,526,595,621,642,664,684,704,739],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":4,"eligibilityCriteria":16,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":42,"lastUpdatePostDateStruct":43,"startDateStruct":46,"completionDateStruct":48,"leadSponsor":50,"locationsCount":53},"100482618","targeted-therapy-directed-by-genetic-testing-in-treating-patients-with-locally-advanced-or-advanced-solid-tumors-the-combomatch-screening-trial-100482618",false,"NCT05564377","Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial","Molecular Analysis for Combination Therapy Choice (ComboMATCH)","Inclusion Criteria:\n\n* Patient must have measurable disease\n* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-2 OR patient must have Lansky performance status of \\>= 50% or Karnofsky performance status of \\>= 50%\n* Patient must be deemed potentially eligible for a ComboMATCH Treatment Trial as assessed by the enrolling provider\n* All patients must have sequencing results available from a National Cancer Institute (NCI) credentialed Designated Laboratory (DL)\n* Patients must have locally advanced or advanced histologically documented solid tumors requiring therapy and meet one of the following criteria:\n\n  * Patients must have progressed on at least one line of standard systemic therapy OR\n  * Patients whose disease has no standard treatment that has been shown to prolong overall survival\n* Patient must meet one of the following requirements:\n\n  * Patients 18 years and older who have tumor amenable to minimal risk image-guided or direct vision biopsy and must be willing and able to undergo a tumor biopsy to obtain samples for research if the patient is to enroll in a ComboMATCH treatment trial OR\n  * Patients 18 years and older who do not have disease that is biopsiable at minimal risk to the patient must confirm availability of an archival tumor tissue specimen for submission for research if the patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:\n\n    * Tissue must have been collected within 12 months prior to registration to the EAY191 Registration Trial\n    * Patient must not have had a Response Evaluation Criteria in Solid Tumors (RECIST) response (complete response \\[CR\\] or partial response \\[PR\\]) to any intervening therapy after collection of the tissue\n    * Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available OR\n  * Patients under 18 years old must confirm availability of an archival tumor tissue specimen for submission for research if patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:\n\n    * Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available\n  * NOTE: See specific ComboMATCH Treatment Trial protocol for tissue collection and management instructions. Performance of the mandatory research biopsy or submission of pre-trial formalin-fixed paraffin-embedded (FFPE) and collection and submission of the blood specimens for the integrated studies will be performed under the consent authority of the specific treatment trial protocol to which the patient is registered. No procedures to collect specimens for research only are to be performed for patients registered to the EAY191 Registration Trial only\n* NOTE: Each ComboMATCH Treatment Trial contains specific eligibility criteria. If patient is found to not be eligible for the assigned ComboMATCH Treatment Trial, indication of ineligibility will trigger re-evaluation and potential assignment to another Treatment Trial","ALL",{"count":19,"type":20},2900,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.",[26,27,28,29,30,31,32,33,34,35,36,37,38,39,40],"Advanced Malignant Solid Neoplasm","Anatomic Stage III Breast Cancer AJCC v8","Anatomic Stage IV Breast Cancer AJCC v8","Locally Advanced Malignant Solid Neoplasm","Malignant Female Reproductive System Neoplasm","Metastatic HER2-Negative Breast Carcinoma","Metastatic Malignant Solid Neoplasm","Recurrent Endometrial Carcinoma","Recurrent Fallopian Tube Carcinoma","Recurrent Malignant Female Reproductive System Neoplasm","Recurrent Malignant Solid Neoplasm","Recurrent Ovarian Carcinoma","Recurrent Primary Peritoneal Carcinoma","Unresectable HER2-Negative Breast Carcinoma","Unresectable Malignant Solid Neoplasm","RECRUITING","2026-08-18",{"date":44,"type":45},"2026-08-19","ACTUAL",{"date":47,"type":45},"2023-04-07",{"date":49,"type":20},"2030-07-01",{"name":51,"class":52},"National Cancer Institute (NCI)","NIH",482,{"id":55,"slug":56,"hasResults":12,"nctId":57,"briefTitle":58,"officialTitle":59,"acronym":60,"eligibilityCriteria":61,"healthyVolunteers":12,"sex":17,"minAge":62,"maxAge":4,"enrollmentInfo":63,"targetDuration":4,"studyType":21,"phases":65,"briefSummary":67,"conditions":68,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":42,"lastUpdatePostDateStruct":165,"startDateStruct":167,"completionDateStruct":169,"leadSponsor":171,"locationsCount":174},"100459958","phase-1-personalized-neoantigen-peptide-based-vaccine-in-combination-with-pembrolizumab-for-treatment-of-advanced-solid-tumors-100459958","NCT05269381","Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors","A Phase I\u002FII Study of Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab in Advanced Solid Tumors (PNeoVCA)","PNeoVCA","Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling.\n\nPHASE I PRE-REGISTRATION, ALL:\n\n* Willing to provide tissue specimens per protocol, or have clinically collected formalin-fixed paraffin-embedded (FFPE) tissue blocks, or available sequencing data available from commercial or research tests\n\n  * NOTE 1: Includes fresh tissue specimen at pre-registration, or with or clinically collected FFPE tissue blocks for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo IRB protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration.\n  * NOTE 2: This criteria will not apply to patients who had sequencing and neoantigen prediction previously completed.\n* Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy\n* Provide written informed consent. For pediatric patients (age 16-17 years):\n\n  * Written informed consent from legal guardian(s) and\u002For child obtained in accordance with local regulations.\n* Willing to return to enrolling institution for follow-up\n* Willing to provide blood specimens for research\n* Negative pregnancy test 7 days prior to pre-registration for persons of childbearing potential.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one ≤ 1 year prior to pre-registration\n* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1\n* Anticipated life expectancy \\> 6 months\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo).\n* The following lab values obtained ≤ 28 days prior to pre-registration:\n\n  * Hemoglobin ≥ 9.0 g\u002FdL (Must be ≥ 7 days after most recent transfusion)\n  * Absolute neutrophil count (ANC) ≥ 1500\u002Fmm\\^3 or ≥ 1.5 X 10\\^9\u002FL\n  * Platelet count ≥ 100,000\u002Fmm\\^3 or ≥ 100 X 10\\^9\u002FL (Must be ≥7 days after most recent transfusion)\n  * Total bilirubin ≤ 1.5 x upper limit of normal (ULN)\n  * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN or ≤ 5 x ULN with liver metastases\n  * Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance must be ≥ 50 ml\u002Fmin using Cockcroft-Gault formula\n  * International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy\n\nPHASE I REGISTRATION, ALL:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained ≤ 14 days prior to registration:\n\n  * Hemoglobin ≥ 9.0 g\u002Fdl\n  * ANC ≥ 1500\u002Fmm\\^3\n  * Platelet count ≥ 100,000\u002Fmm\\^3\n  * Total bilirubin ≤ 1.5 x ULN\n  * ALT and AST ≤ 3 x ULN (≤ 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance ≥ 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood and tissue specimens for research\n* Willing to return to enrolling institution for follow-up\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have also received and progressed on at least one line of prior FDA-approved targeted therapy\n* Negative pregnancy test ≤ 14 days prior to registration for persons of childbearing potential only\n\n  * NOTE: If urine test cannot be confirmed negative, serum pregnancy test will be required\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one ≤ 1 year prior to pre-registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status or NCI CTCAE v5 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nPHASE II PRE-SCREENING COHORT 3 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of adenocarcinoma of the breast with estrogen receptor (ER) \\\u003C 10%, progesterone receptor (PR) \\\u003C 10%, and HER2 negative based on current American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guideline\n* Stage I-III based on 7th edition of TNM staging system from American Joint Committee on Cancer (AJCC)\n* Evidence of residual disease ≥ 1 cm after neoadjuvant pembrolizumab-based chemotherapy on imaging for patients who have not had surgery\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery, willing to provide clinically collected FFPE tissue blocks, or willing to provide available sequencing data available from commercial or research test\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-SCREENING COHORT 4 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of lung NSCLC\n* No actionable EGFR mutations and ALK fusions\n* Stage II or stage III based on AJCC 8th\n* Tumor ≥ 2 cm on pre-surgery evaluation imaging (residual disease ≥ 2 cm after neoadjuvant therapy on pre-surgery evaluation imaging in patient who receives neoadjuvant therapy) for patients who have not had surgery. Patients with or without neoadjuvant chemotherapy or immunotherapy are allowed\n* Provide written informed consent\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-REGISTRATION COHORT 3 (TNBC) ONLY:\n\n* Histologically confirmed residual cancer burden 2 and 3 in surgical specimens\n\nPHASE II PRE-REGISTRATION COHORT 4 (NSCLC) ONLY:\n\n* Tumor without complete pathologic response is confirmed in pathology\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* ECOG PS of 0 or 1\n* Anticipated life expectancy \\> 6 months\n\nPHASE II PRE-REGISTRATION PILOT AND COHORT 5:\n\n* Provide written informed consent. For pediatric patients (age 16-17 years):\n\n  * Written informed consent from legal guardian(s) and\u002For child obtained in accordance with local regulations\n* Willing to proceed with surgery and provide mandatory tissue specimens or previously collected FFPE tissues for complete exome and transcriptome sequencing or available sequencing data available from commercial or research test\n\n  * NOTE: Patients who had sequencing under Mayo IRB protocol #13-000942, #14-004094, or #21-007742 and neoantigens have been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration\n* Negative pregnancy test done ≤ 7 days prior to pre-registration for persons of childbearing potential only\n\n  * NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* Willing to employ a highly effective method of contraception from the time of preregistration through 6 months after the final vaccine cycle\n* ECOG performance status of 0 or 1\n* Anticipated life expectancy of \\> 6 months\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-REGISTRATION COHORT 5 (ILC) ONLY:\n\n* Histologically confirmed invasive lobular carcinoma or other histology with lobular features\n\n  * Histological confirmation of adenocarcinoma of the breast with invasive lobular histology or other histology with lobular features with any estrogen receptor (ER), progesterone receptor (PR), and HER2 status\n  * Stage II-IV based on the 7th edition of TNM staging system from AJCC\n  * Tumor mutational burden ≥ 10 muts\u002FMb either in tissue or blood\n\nPHASE II AND PILOT COHORT 5 REGISTRATION:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Patients will receive ≥ 2 additional cycles of maintenance pembrolizumab\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* Lab values as per Phase I registration criteria obtained ≤ 14 days prior to registration:\n* Provide written informed consent\n* Willing to provide blood specimens for research\n* Willing to return to enrolling institution for follow-up\n* Negative pregnancy test ≤ 14 days prior to registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one ≤ 1 year prior registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status NCI CTCAE v5 grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nExclusion Criteria\n\nALL PHASES:\n\n* Any of the following because study involves investigational agent whose genotoxic, mutagenic and teratogenic effects on developing fetus and newborn are unknown:\n\n  * Pregnant person\n  * Nursing person unwilling to stop breast feeding\n  * Person of childbearing potential unwilling to employ adequate contraception from registration through 6 months after final vaccine cycle\n* Co-morbid systemic illnesses or other severe concurrent disease which, in judgment of investigator, would make patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and toxicity of prescribed regimens\n* History of myocardial infarction ≤ 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.\n* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy\n\nPHASE I PRE-REGISTRATION:\n\n* Acute, reversible effect(s) of prior therapy not recovered to baseline regardless of interval since last treatment\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Psychiatric illness\u002Fsocial situations\n  * Congestive heart failure with New York Heart Association (NYHA) class III or IV moderate to severe objective evidence of cardiovascular disease\n  * Stroke ≤ 3 months prior to pre-registration\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Receiving any other investigational agent which would be considered treatment for primary neoplasm, except pembrolizumab\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy ≤ 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* History of active autoimmune disease (AD) that required systemic treatment in ≤ 30 days (i.e., use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with celiac disease controlled with diet modification are not excluded PHASE I REGISTRATION\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) ≤ 3 weeks prior to cycle 1 day 1 (C1D1) neoantigen vaccinations\n  * Radiation ≤ 2 weeks prior to C1D1 neoantigen vaccinations\n  * Major Surgery ≤ 4 weeks prior to C1D1 neoantigen vaccinations\n  * Received live vaccine ≤ 30 days prior to C1D1 neoantigen vaccinations\n  * NOTE: Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE ≥ Grade 3 treatment-emergent adverse event (TEAE) to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications ≤ 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent permitted in absence of active AD\n* Patients will also be excluded based on tissue\u002FRNA\u002FDNA quality and quantity. If any of the following quality and quantity thresholds are not met, the patient will be excluded:\n\n  * Tumor tissue cellularity ≥ 30%\n  * Sufficient tissue (fresh frozen or FFPE) for both DNA and RNA sequencing with passing cellularity.\n  * ≥ 30% of tumor RNA with fragment sizes are ≥ 200 base pairs (DV200 ≥ 30)\n  * \\\u003C 10% of DNA fragments are smaller than 1 kb\n  * Sufficient amount of both DNA (blood and tumor) and RNA (tumor) for exome sequencing and RNAseq according to the Mayo sequencing core (note: kits and technologies change over time, so these are not fixed numbers)\n* Evidence of leptomeningeal disease or central nervous system metastases that are untreated, symptomatic, or require steroids \\>10 mg daily prednisone equivalent\n\n  * NOTE: Patients with history of stable treated brain metastases are eligible. Stable treated metastases defined as no evidence of progression for ≥4 weeks on brain imaging (MRI or CT scan)\n\nPHASE II PRE-SCREENING:\n\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * CHF with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy ≤ 3 years prior to pre-screening\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* Known history of active AD that has required systemic treatment in the ≤ 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-screening\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n\nPHASE II PRE-REGISTRATION\n\n* Uncontrolled illness including, but not limited to:\n\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy ≤ 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If history of prior malignancy, must not be receiving other specific treatment for cancer\n* Known history of active AD that has required systemic treatment in the ≤ 30 days (i.e., with use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n* Patients will also be excluded based on tissue\u002FRNA\u002FDNA quality and quantity. If any of the following quality and quantity thresholds are not met, patient will be excluded: (1) tumor tissue cellularity equal to or greater than 30%; (2) there are ≥ 2 cores with passing cellularity; (3) ≥ 30% of tumor RNA with fragment sizes are ≥ 200 base pairs (DV200 ≥ 30); (4) \\\u003C 10% of DNA fragments are smaller than 1 kb; and (5) sufficient amount of both DNA (blood and tumor) and RNA (tumor) for exome sequencing and whole transcriptome sequencing (RNAseq) according to Mayo sequencing core. (Kits and technologies change overtime, so these are not fixed numbers.)\n\nPHASE II REGISTRATION\n\n* Evidence of metastatic disease or recurrence\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) ≤ 3 weeks prior to study treatment\n  * Radiation ≤ 2 weeks prior to study treatment\n  * Major surgery ≤ 4 weeks prior to study treatment\n  * Received live vaccine ≤ 30 days prior to study treatment\n\n    * NOTE: Continuation of pembrolizumab per standard of care is allowed\n    * NOTE: Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE ≥ grade 3 TEAE to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy), or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n\nOther inclusion\u002Fexclusion criteria as indicated per protocol not listed here due to limitation in number of characters (text) allowed.","16 Years",{"count":64,"type":20},138,[66,23],"PHASE1","This phase I\u002FII trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.",[27,69,70,71,28,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,29,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,32,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,40,153,154,155,156,157,158,159,160,161,162,163,164],"Anatomic Stage IIIA Breast Cancer AJCC v8","Anatomic Stage IIIB Breast Cancer AJCC v8","Anatomic Stage IIIC Breast Cancer AJCC v8","Clinical Stage III Cutaneous Melanoma AJCC v8","Clinical Stage III Gastric Cancer AJCC v8","Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage III Merkel Cell Carcinoma AJCC v8","Clinical Stage IV Cutaneous Melanoma AJCC v8","Clinical Stage IV Gastric Cancer AJCC v8","Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IV Merkel Cell Carcinoma AJCC v8","Clinical Stage IVA Gastric Cancer AJCC v8","Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IVB Gastric Cancer AJCC v8","Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Locally Advanced Cervical Carcinoma","Locally Advanced Endometrial Carcinoma","Locally Advanced Gastric Adenocarcinoma","Locally Advanced Gastroesophageal Junction Adenocarcinoma","Locally Advanced Head and Neck Squamous Cell Carcinoma","Locally Advanced Hepatocellular Carcinoma","Locally Advanced Lung Non-Small Cell Carcinoma","Locally Advanced Melanoma","Locally Advanced Merkel Cell Carcinoma","Locally Advanced Renal Cell Carcinoma","Locally Advanced Skin Squamous Cell Carcinoma","Locally Advanced Triple-Negative Breast Carcinoma","Locally Advanced Unresectable Breast Carcinoma","Locally Advanced Unresectable Cervical Carcinoma","Locally Advanced Unresectable Gastric Adenocarcinoma","Locally Advanced Unresectable Gastroesophageal Junction Adenocarcinoma","Locally Advanced Unresectable Renal Cell Carcinoma","Locally Advanced Urothelial Carcinoma","Metastatic Cervical Carcinoma","Metastatic Endometrial Carcinoma","Metastatic Gastric Adenocarcinoma","Metastatic Gastroesophageal Junction Adenocarcinoma","Metastatic Head and Neck Squamous Cell Carcinoma","Metastatic Hepatocellular Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Melanoma","Metastatic Merkel Cell Carcinoma","Metastatic Renal Cell Carcinoma","Metastatic Skin Squamous Cell Carcinoma","Metastatic Triple-Negative Breast Carcinoma","Metastatic Urothelial Carcinoma","Skin Squamous Cell Carcinoma","Stage III Cervical Cancer AJCC v8","Stage III Hepatocellular Carcinoma AJCC v8","Stage III Lung Cancer AJCC v8","Stage III Renal Cell Cancer AJCC v8","Stage IIIA Cervical Cancer AJCC v8","Stage IIIA Hepatocellular Carcinoma AJCC v8","Stage IIIA Lung Cancer AJCC v8","Stage IIIA Uterine Corpus Cancer AJCC v8","Stage IIIB Cervical Cancer AJCC v8","Stage IIIB Hepatocellular Carcinoma AJCC v8","Stage IIIB Lung Cancer AJCC v8","Stage IIIB Uterine Corpus Cancer AJCC v8","Stage IIIC Lung Cancer AJCC v8","Stage IIIC Uterine Corpus Cancer AJCC v8","Stage IIIC1 Uterine Corpus Cancer AJCC v8","Stage IIIC2 Uterine Corpus Cancer AJCC v8","Stage IV Cervical Cancer AJCC v8","Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","Stage IV Lung Cancer AJCC v8","Stage IV Renal Cell Cancer AJCC v8","Stage IVA Cervical Cancer AJCC v8","Stage IVA Hepatocellular Carcinoma AJCC v8","Stage IVA Lung Cancer AJCC v8","Stage IVA Uterine Corpus Cancer AJCC v8","Stage IVB Cervical Cancer AJCC v8","Stage IVB Hepatocellular Carcinoma AJCC v8","Stage IVB Lung Cancer AJCC v8","Stage IVB Uterine Corpus Cancer AJCC v8","Triple-Negative Breast Carcinoma","Unresectable Cervical Carcinoma","Unresectable Endometrial Carcinoma","Unresectable Gastric Adenocarcinoma","Unresectable Gastroesophageal Junction Adenocarcinoma","Unresectable Head and Neck Squamous Cell Carcinoma","Unresectable Hepatocellular Carcinoma","Unresectable Lung Non-Small Cell Carcinoma","Unresectable Melanoma","Unresectable Merkel Cell Carcinoma","Unresectable Renal Cell Carcinoma","Unresectable Skin Squamous Cell Carcinoma","Unresectable Triple-Negative Breast Carcinoma","Unresectable Urothelial Carcinoma","Breast Adenocarcinoma","Stage III Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage IV Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","Invasive Breast Lobular Carcinoma",{"date":166,"type":45},"2026-08-20",{"date":168,"type":45},"2022-03-31",{"date":170,"type":20},"2028-03-31",{"name":172,"class":173},"Mayo Clinic","OTHER",1,{"id":176,"slug":177,"hasResults":12,"nctId":178,"briefTitle":179,"officialTitle":180,"acronym":4,"eligibilityCriteria":181,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":183,"targetDuration":4,"studyType":21,"phases":185,"briefSummary":187,"conditions":188,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":191,"lastUpdatePostDateStruct":192,"startDateStruct":194,"completionDateStruct":196,"leadSponsor":198,"locationsCount":200},"100554545","phase-3-testing-proton-craniospinal-radiation-therapy-versus-the-usual-radiation-therapy-for-leptomeningeal-metastasis-radiate-lm-trial-100554545","NCT06500481","Testing Proton Craniospinal Radiation Therapy Versus the Usual Radiation Therapy for Leptomeningeal Metastasis, RADIATE-LM Trial","A Phase III Randomized Clinical Trial of Proton Craniospinal Irradiation Versus Involved-Field Radiotherapy for Patients With Breast Cancer or Non-Small Cell Lung Cancer Leptomeningeal Metastasis (Radiate-LM)","Inclusion Criteria:\n\n* PRIOR TO STEP 1 REGISTRATION\n* Patients with pathologically (histologically or cytologically) proven diagnosis of breast cancer or NSCLC\n* Patients must have newly diagnosed leptomeningeal metastasis established through at least one of the following:\n\n  * Positive CSF cytology for malignancy\n\n    * CSF cytology with suspicious cells is considered positive; CSF cytology with atypical cells is considered equivocal and not positive\n  * Patients with an equivocal or negative CSF cytology result, or not suitable for CSF sampling, radiographic diagnosis of leptomeningeal metastasis with linear and\u002For nodular disease and documentation of typical clinical signs (European Association of Neuro-Oncology \\[EANO\\]-European Society for Medical Oncology \\[ESMO\\] Diagnostic Criteria Type IIA-IIC) is required\n\n    * Patients with typical clinical signs of leptomeningeal metastasis may have one or more of the following symptoms and signs: headache, nausea, vomiting, mental status change, gait difficulty, cranial nerve palsy, diplopia, visual change, hearing loss, radicular weakness, radicular sensory change, urinary retention, saddle anesthesia, constipation, neck pain, and back pain\n  * For patients with prior history of immunotherapy or current immunotherapy, CSF sampling rather than just MRI enhancement is strongly recommended to exclude immune-related aseptic meningitis\n* Patients must be candidates for radiation therapy for the treatment of leptomeningeal metastasis\n* Age ≥ 18\n* PRIOR TO STEP 2 REGISTRATION\n* Note: Step 2 registration must occur no later than 30 calendar days after step 1 registration\n* Financial clearance for proton therapy treatment\n* Patients must have systemic disease evaluation through standard of care imaging for example CT chest\u002Fabdomen\u002Fpelvis or body PET\u002FCT\n* Karnofsky performance status ≥ 60\n* Not pregnant and not nursing\n\n  * Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal\n* Hemoglobin ≥ 8.0 g\u002Fdl (Note: The use of transfusion or other intervention to achieve hemoglobin \\[Hgb\\] ≥ 8.0 g\u002Fdl is acceptable)\n* Absolute neutrophil count (ANC) ≥ 1,000\u002Fmm\\^3 (Note: the use of granulocyte-colony stimulating factor or other intervention to achieve ANC ≥ 1,000\u002Fmm\\^3 is acceptable)\n* Platelets ≥ 100,000\u002Fmm\\^3 (Note: the use of transfusion or other intervention to achieve platelets ≥ 100,000\u002Fmm\\^3 is acceptable)\n* Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (patients with known Gilbert disease without other clinically significant liver abnormalities are not excluded)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) and alanine transaminase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 × ULN\n* No prior radiation therapy to the spinal cord with equivalent dose in 2 gray (Gy) fractions (EQD2) more than 40Gy or cauda equina with EQD2 more than 50Gy using alpha\u002Fbeta ratio of 3\n* No prior treatment for leptomeningeal metastasis (note: prior CNS treatment for other non-leptomeningeal disease is allowed)\n* No history of unstable angina requiring hospitalization in the last 3 months\n* No history of myocardial infarction within the last 3 months\n* New York Heart Association Functional Classification II or better (New York Heart Association \\[NYHA\\] Functional Classification III\u002FIV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)\n* No active infection currently requiring intravenous (IV) antibiotic management\n* No active chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy\n* No CTCAE v5.0 ≥ grade 2 encephalopathy","18 Years",{"count":184,"type":20},115,[186],"PHASE3","This phase III trial compares proton craniospinal irradiation (pCSI) to involved-field radiation therapy (IFRT) for the treatment of breast or non-small cell lung cancer that has spread from where it first started to the cerebrospinal fluid filled space that surrounds the brain and spinal cord (leptomeningeal metastasis). Patients with leptomeningeal metastasis (LM) may develop multiple areas of nervous system (neurologic) impairment that can be life-threatening. Radiation therapy (RT) effectively relieves local symptoms due to LM. RT uses high energy radiography (x-rays), particles, or radioactive seeds to kill cancer cells and shrink tumors. IFRT is commonly used to treat symptoms of LM. IFRT is radiation treatment that uses x-rays to treat specific areas of LM and to relieve and\u002For prevent symptoms. pCSI uses protons that can be directed with more accuracy than x-rays which allows treatment of the entire central nervous system space containing the cerebrospinal fluid (CSF), brain, and spinal cord. The pCSI treatment could delay the worsening of LM. Giving pCSI may be better than IFRT in treating LM in patients with breast or non-small cell lung cancer.",[28,189,108,190,135],"Metastatic Breast Carcinoma","Metastatic Malignant Neoplasm in the Leptomeninges","2026-08-14",{"date":193,"type":45},"2026-08-17",{"date":195,"type":45},"2025-03-04",{"date":197,"type":20},"2033-07-31",{"name":199,"class":173},"NRG Oncology",58,{"id":202,"slug":203,"hasResults":12,"nctId":204,"briefTitle":205,"officialTitle":206,"acronym":4,"eligibilityCriteria":207,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":208,"targetDuration":4,"studyType":21,"phases":210,"briefSummary":211,"conditions":212,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":191,"lastUpdatePostDateStruct":215,"startDateStruct":216,"completionDateStruct":218,"leadSponsor":220,"locationsCount":221},"100554543","phase-3-testing-longer-duration-radiation-therapy-versus-the-usual-radiation-therapy-in-patients-with-cancer-that-has-spread-to-the-brain-100554543","NCT06500455","Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain","Phase III Trial of Single Fraction Stereotactic Radiosurgery (SRS) Versus Fractionated SRS (FSRS) for Intact Brain Metastases","Inclusion Criteria:\n\n* Pathologically (histologically or cytologically) proven diagnosis of one of the following solid tumor malignancies within 5 years prior to registration:\n\n  * Non-small cell lung cancer\n  * Melanoma\n  * Breast cancer\n  * Renal cell carcinoma\n  * Gastrointestinal cancer\n  * If the original histologic proof of malignancy is greater than 5 years, then more recent pathologic confirmation (e.g., from a systemic site or brain metastasis) or unequivocal imaging confirmation of extracranial metastatic disease (e.g. CT of the chest\u002Fabdomen\u002Fpelvis, positron emission tomography \\[PET\\]\u002FCT, etc.) is required\n* Patients must have at least 1 and up to 8 total intact brain metastases detected on a contrast-enhanced MRI performed ≤ 21 days prior to registration\n* At least 1 of the up to 8 lesions must be a study eligible lesion, defined as lesion with a maximum diameter as measured on any orthogonal plane (axial, sagittal, coronal) of ≥ 1.0 cm and ≤ 3.0 cm\n* All brain metastases must be located outside of the brainstem and ≥ 5 mm from the optic nerves or optic chiasm and ≤ 3.0 cm in maximum dimension\n\n  * Note: brainstem metastases per the MRI within 21 days of registration are an exclusion criterion; however, if the MRI used for treatment planning performed within 7 days of SRS\u002FFSRS reveals a brainstem metastasis, the patient remains eligible if the patient is considered an appropriate radiosurgery candidate per the local investigator\n* Patients must have a diagnosis-specific graded prognostic assessment ≥ 1.5\n* No more than 2 lesions planned for resection if clinically indicated\n* No known leptomeningeal disease (LMD)\n\n  * Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive cerebrospinal fluid (CSF) cytology and\u002For unequivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion\n* Age ≥ 18 years\n* Karnofsky performance status (KPS) ≥ 60\n* Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal\n* No prior radiotherapy to the brain (partial or whole brain irradiation, SRS, FSRS, or prophylactic cranial irradiation \\[PCI\\])\n* New York Heart Association Functional Classification II or better (NYHA Functional Classification III\u002FIV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)\n* No active infection currently requiring intravenous (IV) antibiotic management\n* No hepatic insufficiency resulting in clinical jaundice and\u002For coagulation defects\n* No chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy",{"count":209,"type":20},269,[186],"This phase III trial compares the effectiveness of fractionated stereotactic radiosurgery (FSRS) to usual care stereotactic radiosurgery (SRS) in treating patients with cancer that has spread from where it first started to the brain. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. FSRS delivers a high dose of radiation to the tumor over 3 treatments. SRS is a type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. FSRS may be more effective compared to SRS in treating patients with cancer that has spread to the brain.",[28,189,213,108,214,32,109,111,135,136],"Metastatic Digestive System Carcinoma","Metastatic Malignant Neoplasm in the Brain",{"date":193,"type":45},{"date":217,"type":45},"2024-12-12",{"date":219,"type":20},"2033-06-30",{"name":199,"class":173},270,{"id":223,"slug":224,"hasResults":12,"nctId":225,"briefTitle":226,"officialTitle":227,"acronym":4,"eligibilityCriteria":228,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":229,"targetDuration":4,"studyType":21,"phases":231,"briefSummary":232,"conditions":233,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":234,"lastUpdatePostDateStruct":235,"startDateStruct":236,"completionDateStruct":238,"leadSponsor":240,"locationsCount":242},"100555897","phase-2-hippocampal-avoidance-in-craniospinal-irradiation-for-the-treatment-of-leptomeningeal-metastases-from-breast-cancer-or-non-small-cell-lung-cancer-100555897","NCT06518057","Hippocampal Avoidance in Craniospinal Irradiation for the Treatment of Leptomeningeal Metastases From Breast Cancer or Non-small Cell Lung Cancer","A Multi-Center Phase 2 Study of Hippocampal Avoidance in Craniospinal Irradiation for Leptomeningeal Metastases From Solid Tumors","Inclusion Criteria:\n\n* Patients with breast cancer or NSCLC malignancies with leptomeningeal metastases established radiographically and\u002For through CSF cytology\n* Patients who are candidates for radiation therapy for the treatment of leptomeningeal metastases\n* Patients ≥ 18 years old\n* Karnofsky performance status (KPS) ≥ 60 or Eastern Cooperative Oncology Group (ECOG) ≥ 2\n* The patient is able to provide informed consent\n* Hemoglobin \\> 8 g\u002FdL\n* Absolute neutrophil count \\> 1,000\u002Fmm\n* Platelet count \\> 100,000\u002Fmm\n* Participants born female at birth must either be of non-reproductive potential (i.e. post-menopausal by history \\[≥ 60 years old, or with no menses for \\> 1 year without an alternative medical cause\\], OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum \u002Furine pregnancy test within 3 weeks prior to starting radiation therapy (RT)\n* Patients with reproductive potential must agree to practice two highly effective contraceptive methods\n\nExclusion Criteria:\n\n* Patients with multiple, serious major neurologic deficits per physician\u002Finvestigator assessment including encephalopathy\n* Patients with extensive systemic disease and without reasonable systemic treatment options\n* Patients who are unable to undergo MRI brain and spine with gadolinium contrast\n* Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances\n* Gross ventricular disease\n* Brain metastases within 5 mm of the hippocampal contours not previously treated\n* Pregnant or lactating women",{"count":230,"type":20},22,[23],"This phase II clinical trial studies how well craniospinal irradiation (CSI) with hippocampal avoidance, using proton therapy or volumetric modulated arc therapy (VMAT), works in treating patients with breast cancer or non-small cell lung cancer (NSCLC) that has spread from the original (primary) tumor to the cerebrospinal fluid (CSF) and meninges (thin layers of tissue that cover and protect the brain and spinal cord) (leptomeningeal metastases). Radiation therapy is an effective treatment in relieving localized symptoms caused by leptomeningeal metastases. However, the type of radiation therapy typically used does not prevent the spread of leptomeningeal disease. CSI (radiation therapy directed at the brain and spinal cord to kill tumor cells) may be able to target all of the areas of possible leptomeningeal tumor spread. CSI may however result in significant neurological side effects due to radiation damage to a part of the brain called the hippocampus. Hippocampal avoidance (HA) reduces the amount of radiation to the hippocampus. Proton or VMAT CSI with HA may be an effective treatment while reducing neurological side effects for patients with leptomeningeal metastases from breast cancer and NSCLC.",[28,189,108,190,135],"2026-08-12",{"date":191,"type":45},{"date":237,"type":45},"2025-03-03",{"date":239,"type":20},"2028-07-01",{"name":241,"class":173},"University of Washington",3,{"id":244,"slug":245,"hasResults":12,"nctId":246,"briefTitle":247,"officialTitle":248,"acronym":4,"eligibilityCriteria":249,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":250,"targetDuration":4,"studyType":21,"phases":252,"briefSummary":253,"conditions":254,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":257,"lastUpdatePostDateStruct":258,"startDateStruct":259,"completionDateStruct":261,"leadSponsor":263,"locationsCount":174},"100556489","phase-2-adaptive-therapy-with-capecitabine-for-treatment-of-metastatic-er-positive-her2-negative-breast-cancer-100556489","NCT06525766","Adaptive Therapy With Capecitabine for Treatment of Metastatic ER Positive, HER2 Negative Breast Cancer","Single Arm Pilot Trial of Adaptive Therapy (AT) With Capecitabine for the Treatment of Metastatic Estrogen Receptor Positive, Hormone Refractory Breast Cancer","Inclusion Criteria:\n\n* PRE-REGISTRATION: Provide written informed consent Note: Pre-registration should occur prior to screening research blood draws being completed\n* PRE-REGISTRATION: Provider anticipates the patient will begin on capecitabine within 14 days or has started capecitabine within the past 42 days and has had a maximum of two cycles Note: Pre-registration should occur prior to screening research blood draws being completed\n\nREGISTRATION - INCLUSION CRITERIA\n\n* Age ≥ 18 years\n* Histological confirmation of estrogen-receptor positive (ER+), HER2-negative overexpression or amplification negative as per American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guidelines, metastatic breast cancer\n* Measurable disease. Bone only disease allowed if associated with soft tissue component that is measurable by Response Evaluation Criteria is Solid Tumors (RECIST) 1.1 criteria\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2\n* Hemoglobin ≥ 9.0 g\u002FdL (obtained ≤ 14 days prior to registration), no transfusions allowed ≤ 14 days prior to registration\n* Absolute neutrophil count (ANC) ≥ 1500\u002Fmm\\^3 (obtained ≤ 14 days prior to registration)\n* Platelet count ≥ 100,000\u002Fmm\\^3 (obtained ≤ 14 days prior to registration)\n* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 14 days prior to registration)\n* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 14 days prior to registration)\n* Calculated creatinine clearance ≥ 30 ml\u002Fmin using the Cockcroft-Gault formula (obtained ≤ 14 days prior to registration)\n* Negative serum or urine pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only. NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* Provide written informed consent\n* Ability to complete questionnaire(s) by themselves or with assistance\n* Willingness to provide mandatory blood specimens for correlative research\n* Ability to undergo re-staging CT scans as required by the protocol\n\n  * Note: for patients who have had up to two cycles of capecitabine prior to joining the study, they must have had their initial CT imaging completed within 28 days of their first dose of capecitabine\n* Willing to return to enrolling institution at the specified frequency for follow-up (during the active monitoring phase of the study)\n* Cohort 2 only: Stable disease, partial or complete response on imaging after beginning capecitabine\n\nExclusion Criteria:\n\n* Prior chemotherapy or use of antibody drug conjugate in the metastatic setting\n\n  * Note - Cohort 2 only: Patients can have had up to two cycles of capecitabine before joining the study\n* Any of the following, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:\n\n  * Pregnant persons\n  * Nursing persons\n  * Persons of childbearing potential who are unwilling to employ adequate contraception\n* Any of the following prior therapies:\n\n  * Major surgery ≤ 3 weeks prior to registration\n  * Radiation therapy ≤ 2 weeks prior to registration\n* Evidence of visceral crisis or impending cord compression\n* Evidence of uncontrolled brain metastasis requiring whole brain irradiation or intervention\n* Uncontrolled intercurrent illness including, but not limited to:\n\n  * ongoing or active infection\n  * symptomatic congestive heart failure\n  * unstable angina pectoris\n  * uncontrolled cardiac arrhythmia\n  * chronic oxygen dependence\n  * respiratory failure\n  * or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm\n* Other active malignancy ≤ 3 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n* If there is a history of prior malignancy, they must not be receiving other cancer specific treatment. Except for antiestrogen treatment (aromatase inhibitors or selective estrogen modulators) for their cancer are permitted if they meet other eligibility criteria. Denosumab and zoledronic acid, are permitted as established adjunct therapies per guidelines\n* History of myocardial infarction ≤ 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias\n* Patients known to have certain homozygous or compound heterozygous dihydropyrimidine dehydrogenase (DPYD) variants that result in complete absence of deoxypyridinoline (DPD) activity. Test results do not need to be available prior to registration\n* History of severe hypersensitivity reactions to fluorouracil or capecitabine",{"count":251,"type":20},35,[23],"This phase II trial evaluates the effect of capecitabine on tumor response using imaging and tumor markers to adjust dose (adaptive therapy) in patients with estrogen receptor (ER) positive, HER2 negative breast cancer that has spread from where it first started to other areas in the body (metastatic). Capecitabine is in a class of medications called antimetabolites. It is taken up by tumor cells and breaks down into fluorouracil, a substance that kills tumor cells. Adaptive therapy with capecitabine based on tumor burden response may slow or stop the growth of tumor cells in patients with metastatic ER positive, HER2 negative breast cancer.",[28,255,31,256],"Estrogen-receptor-positive Breast Cancer","Metastatic Breast Cancer","2026-08-10",{"date":234,"type":45},{"date":260,"type":45},"2025-10-01",{"date":262,"type":20},"2030-10-15",{"name":172,"class":173},{"id":265,"slug":266,"hasResults":12,"nctId":267,"briefTitle":268,"officialTitle":269,"acronym":4,"eligibilityCriteria":270,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":271,"targetDuration":4,"studyType":21,"phases":273,"briefSummary":274,"conditions":275,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":276,"lastUpdatePostDateStruct":277,"startDateStruct":279,"completionDateStruct":281,"leadSponsor":283,"locationsCount":284},"100471739","phase-1-testing-the-addition-of-anti-cancer-drug-zen003694-zen-3694-and-pd-1-inhibitor-pembrolizumab-to-standard-chemotherapy-nab-paclitaxel-treatment-in-patients-with-advanced-triple-negative-breast-cancer-100471739","NCT05422794","Testing the Addition of Anti-Cancer Drug, ZEN003694 (ZEN-3694) and PD-1 Inhibitor (Pembrolizumab), to Standard Chemotherapy (Nab-Paclitaxel) Treatment in Patients With Advanced Triple-Negative Breast Cancer","A Phase 1b Trial of ZEN003694 (ZEN-3694) With Pembrolizumab and Nab-Paclitaxel in Patients With Metastatic Triple-Negative Breast Cancer","Inclusion Criteria:\n\n* Participants must have a histologically or cytologically confirmed diagnosis of TNBC based on standard criteria for the disease:\n\n  * Estrogen receptor (ER) and progesterone receptor (PR) \\\u003C 10% by immunohistochemistry (IHC), and HER2-negative (per current American Society of Clinical Oncology \\[ASCO\\]\u002FCollege of American Pathologists \\[CAP\\] guidelines)\n  * If there is more than one histological result available, the most recent sample with ER, PR and HER2 results will be considered for inclusion\n  * Patients who have not had ER, PR and HER2 testing and thus, ER, PR and HER2 status is unknown, are not eligible\n  * Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation\n* Participants must have disease that is unresectable locally advanced or metastatic\n* DOSE ESCALATION COHORT: Known PD-L1 status is not required prior to study enrollment. Central PD-L1 testing (on archival tumor tissue) will occur retrospectively\n* DOSE ESCALATION COHORT: Any number of prior lines of therapy are allowed in the metastatic setting. Prior immune checkpoint inhibitor allowed in any setting\n* DOSE ESCALATION COHORT: Evaluable or measurable disease per RECIST 1.1 criteria\n* DOSE EXPANSION COHORT: PD-L1 status must be negative. Standard local testing with any PD-L1 antibody that has been validated in a Clinical Laboratory Improvement Act (CLIA)- certified environment will be acceptable for including patients on trial. Primary or metastatic samples may be tested for PD-L1 status. Central confirmation will occur retrospectively. For patients in whom a baseline research tumor tissue biopsy is not performed (e.g. site of disease is not safely accessible), archival tissue should be provided for central confirmatory PD-L1 testing\n* DOSE EXPANSION COHORT: 0-1 prior lines of systemic therapy in the metastatic setting\n* DOSE EXPANSION COHORT: Participants must have measurable disease per RECIST 1.1 criteria\n* DOSE EXPANSION COHORT: Participants must have disease that is amenable to biopsy as judged by the treating investigator and must be willing to undergo pre- and on-treatment tumor biopsies, if safely accessible\n* Age \\>= 18 years\n\n  * Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with nab-paclitaxel and pembrolizumab (MK-3475) in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2 (Karnofsky \\>= 60%)\n* Absolute neutrophil count \\>= 1,000\u002FmcL\n* Platelets \\>= 100,000\u002FmcL\n* Hemoglobin \\>= 9 g\u002FdL or \\>= 5.6 mmol\u002FL\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN) (or =\\\u003C 2.0 x ULN in patients with documented Gilbert's Syndrome)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) \u002F alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 3.0 x institutional ULN or ≤ 5.0 x institutional ULN for participants with documented liver metastases\n* Serum or plasma creatinine =\\\u003C 1.5 x institutional ULN OR glomerular filtration rate (GFR) \\>= 60 mL\u002Fmin (based on the calculated chronic kidney disease epidemiology (CKD-EPI) glomerular filtration rate estimation\n* International normalized ratio (INR) or prothrombin time (PT): =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants\n* Activated partial thromboplastin time (aPTT): =\\\u003C 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial as long as their anti-retroviral therapy does not have the potential for drug-drug interactions as judged by the treating investigator\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with history of treated central nervous system (CNS) metastases are eligible, provided they meet the following criteria:\n\n  * Disease outside the CNS is present\n  * Recovery from acute toxicity associated with the treatment to =\\\u003C Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1 or baseline (with the exception of alopecia), with no requirement for escalating doses of corticosteroids over the past 7 days\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer are allowed\n* Patients should be New York Heart Association Functional Classification of class 2B or better\n* Peripheral neuropathy grade =\\\u003C 1\n* Ability to swallow and retain oral medications\n* Participants may not have had cytotoxic chemotherapy, immunotherapy, major surgery (other than diagnostic surgery, dental surgery or stenting), or other investigational therapy within 3 weeks prior to entering the study\n* Participants may not have had radiotherapy within 1 week prior to entering the study. Patients may not have had \\> 25% of their bone marrow radiated. Stereotactic radiosurgery (SRS) within 1 week prior to entering the study will be allowed\n* Participants may not have received tyrosine kinase inhibitors (TKIs) or small molecules within 5 half-lives or 2 weeks (whichever is shorter) of study entry\n* Patients who have experienced adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) must have recovered, with the exception of alopecia or as otherwise specified in the eligibility criteria\n* The effects of the combination of ZEN003694 (ZEN-3694) and MK-3475 on the developing human fetus are unknown. For this reason and because BETi and PD-1 blocking agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after study completion. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of ZEN003694 (ZEN-3694), MK-3475 and nab-Paclitaxel administration. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 2 weeks prior to registration. Childbearing potential is defined as: participants who have not reached a postmenopausal state (\\>= 12 continuous months of amenorrhea with no identified cause other than menopause) and have not undergone surgical sterilization (removal of ovaries and\u002For uterus)\n* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and\u002For family member available will also be eligible\n\nExclusion Criteria:\n\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694), nab-paclitaxel, or pembrolizumab\n* Patients with uncontrolled intercurrent illness\n* Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment\n* Any gastrointestinal (GI) disorder that may affect absorption of oral medications in the opinion of the treating investigator, such as malabsorption syndrome or major bowel or stomach resection\n* Pregnant women are excluded from this study because ZEN003694 (a BETi agent) and MK-3475 have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694 (ZEN-3694), breastfeeding should be discontinued if the mother is treated with ZEN003694 (ZEN-3694). These potential risks may also apply to MK-3475 and nab-paclitaxel\n* Patients who have previously received ZEN003694 (ZEN-3694) or who have been treated with an investigational BET inhibitor\n* DOSE EXPANSION COHORT: Prior exposure to immune checkpoint inhibitors in the metastatic setting. PD-1 or PD-L1 inhibitors in the neo-\u002Fadjuvant setting are allowed if at least 12 months have elapsed since the end of adjuvant systemic treatment to development of metastatic disease\n* DOSE EXPANSION COHORT: Prior exposure to taxane-based therapy in the metastatic setting. Taxane in the neo-\u002Fadjuvant setting is allowed if at least 12 months have elapsed since the end of adjuvant systemic treatment to development of metastatic disease\n* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694 (ZEN-3694). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* Patients receiving any medications or substances that are Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed\n* Patients who have had a bone-targeted radionuclide within 6 weeks of the first dose of ZEN003694 (ZEN-3694)\n* Myocardial infarction or unstable angina within 6 months prior to the first dose of ZEN003694 (ZEN-3694)\n* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the study principal investigator (PI)\n* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis\n* Has a known history of active tuberculosis (TB)\n* Has received a live vaccine within 30 days of planned treatment start. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella\u002Fzoster, yellow fever, rabies, Bacille Calmette-Guerin (BCG), and typhoid vaccine. Seasonal flu vaccines that do not contain live virus are permitted. Coronavirus disease-2019 (COVID-19) vaccines received within the last 30 days are also permitted\n* Participants with known or suspected extensive bone marrow infiltration per radiographic assessment, laboratory assessment, or bone marrow sampling (e.g., aspiration or biopsy), determined to be clinically significant by the treating investigator",{"count":272,"type":20},57,[66],"This phase Ib trial tests the safety and tolerability of ZEN003694 in combination with an immunotherapy drug called pembrolizumab and the usual chemotherapy approach with nab-paclitaxel for the treatment of patients with triple negative-negative breast cancer that has spread to other parts of the body (advanced). Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Immunotherapy with monoclonal antibodies, such as pembrolizumab may help the body's immune system attach the cancer and may interfere with the ability of tumor cells to grow and spread. ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that over produce BET protein. Combination therapy with ZEN003694 pembrolizumab immunotherapy and nab-paclitaxel chemotherapy may help shrink or stabilize cancer for longer than chemotherapy alone.",[27,28,95,113,157],"2026-08-08",{"date":278,"type":45},"2026-08-11",{"date":280,"type":45},"2023-05-18",{"date":282,"type":20},"2027-03-31",{"name":51,"class":52},6,{"id":286,"slug":287,"hasResults":12,"nctId":288,"briefTitle":289,"officialTitle":290,"acronym":4,"eligibilityCriteria":291,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":292,"targetDuration":4,"studyType":21,"phases":294,"briefSummary":295,"conditions":296,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":298,"lastUpdatePostDateStruct":299,"startDateStruct":300,"completionDateStruct":302,"leadSponsor":304,"locationsCount":305},"100332337","testing-the-addition-of-an-individualized-vaccine-to-durvalumab-and-tremelimumab-and-chemotherapy-in-patients-with-metastatic-triple-negative-breast-cancer-100332337","NCT03606967","Testing the Addition of an Individualized Vaccine to Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer","Randomized Phase 2 Clinical Trial of Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab + Neoantigen Vaccine vs. Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab in Patients With Metastatic Triple Negative Breast Cancer","Inclusion Criteria:\n\n* Patients must have a histologically confirmed diagnosis of metastatic invasive triple negative breast cancer. Patients with clinical and\u002For radiologic suspicion of metastatic TNBC can be consented prior to this confirmation.\n* Estrogen receptor (ER) and progesterone receptor (PR) less than Allred score of 3 OR less than 1% positive staining cells in the invasive component of the tumor.\n* HER2 negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+.\n* PD-L1 negative by a Clinical Laboratory Improvement Act (CLIA) approved laboratory using compatible assays appropriate for treatment decisions.\n* Patients may have measurable or evaluable disease.\n* Patients must be willing to undergo biopsy and have accessible lesions for a new biopsy, or they must have sufficient tissue available from a biopsy performed for standard of care (specifications below). If patient does not have enough archived tissue available, a new biopsy is required. A tumor specimen obtained from relapsed primary, metastatic, or locally advanced sites of disease (if applicable) must be submitted. Acceptable samples include core needle biopsies for deep tumor tissue (minimum 4 cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. Formalin-fixed, paraffin-embedded (FFPE) tumor specimens in paraffin blocks are preferred; FFPE tumor tissue sections on slides may be provided if sufficient material (15 x 10μ, unstained) is available. Fine-needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and lavage samples are not acceptable.\n* No prior therapy for metastatic TNBC. Patients who have received taxane-based adjuvant therapy are required to have a disease-free interval of at least 12 months after completion of taxane therapy.\n* Age \\>= 18 years. Because no dosing or adverse event data are currently available on the use of durvalumab (MEDI4736) and tremelimumab in combination with neoantigen vaccine in patients \\\u003C 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 1 (Karnofsky \\>= 60%).\n* Body weight \\> 30 kg.\n* Must have a life expectancy of at least 12 weeks.\n* Absolute neutrophil count \\>= 1,500\u002FmcL.\n* Platelets \\>= 100,000\u002FmcL.\n* Hemoglobin \\>= 9.0 g\u002FdL.\n* Serum bilirubin =\\\u003C 1.5 x institutional upper limit of normal.\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =\\\u003C 5 x institutional upper limit of normal.\n* Calculated creatinine clearance \\> 40 mL\u002Fmin by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.\n* Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:\n\n  * Women \\\u003C 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).\n  * Women \\>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \\> 1 year ago, had chemotherapy-induced menopause with last menses \\> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).\n* The effects of durvalumab (MEDI4736) and tremelimumab and neoantigen vaccine on the developing human fetus are unknown. For this reason and because these agents may be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 180 days after completion of durvalumab (MEDI4736) and tremelimumab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.\n* Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.\n* Human immunodeficiency virus (HIV)-positive patients are eligible provided they have a negative viral load, CD4 count \\> 250, and are on a stable antiretroviral regimen.\n* Ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity who have a close caregiver or legal guardian are also eligible with the consent of the caregiver\u002Fguardian.\n\nExclusion Criteria:\n\n* Patients who are not considered to be candidates for carboplatin + gemcitabine for first line therapy of their metastatic triple negative breast cancer are not eligible.\n* Patients who have had chemotherapy, radiotherapy (to more than 30% of the bone marrow), or biologic therapy within 30 days (42 days for nitrosoureas or mitomycin C) prior to entering the study.\n* Patients who have received prior immunotherapy for metastatic disease.\n* Patients who have not recovered from grade \\>= 2 adverse events due to prior anti-cancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.\n\n  * Patients with grade \\>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician.\n* Patients with grade \\>= 2 endocrinological adverse events (AEs), (e.g., hypothyroidism, adrenal insufficiency, hypopituitarism, or diabetes mellitus), must have been on a stable dose of supplemental therapy for at least 2 weeks before screening to be eligible for this study, and the endocrinological AE must be stable in the opinion of the treating physician.\n* Patients who are receiving any other investigational agents or who have received an investigational agent within the last 30 days.\n* Receipt of live attenuated vaccination within 6 months prior to study entry or within 30 days of receiving durvalumab (MEDI4736) and tremelimumab.\n\n  * Note: Patients, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of study treatment.\n* Major surgical procedure within 28 days prior to the first dose of durvalumab (MEDI4736) and tremelimumab. Local surgery of isolated lesions for palliative intent is acceptable.\n* Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab (MEDI4736) or tremelimumab. The following are exceptions to this criterion:\n\n  * Intranasal, inhaled, topical steroids or local steroid injections (e.g. intra-articular injection)\n  * Systemic corticosteroids at physiological doses which are not to exceed 10 mg\u002Fday of prednisone or an equivalent corticosteroid\n  * Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)\n  * Steroids for symptoms from brain metastases as defined.\n* Spinal cord compression or active brain metastases and\u002For carcinomatous meningitis. Subjects who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to registration are eligible if they meet all of the following criteria:\n\n  * Residual neurological symptoms have resolved to grade =\\\u003C 2\n  * On stable doses of dexamethasone, if applicable and if acceptable in the opinion of the treating physician\n  * Follow-up MRI performed after surgery or completion of radiation therapy and prior to registration shows no new lesions.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab (MEDI4736) and tremelimumab. Known allergy, or history of serious adverse reaction to vaccines, such as anaphylaxis, hives or respiratory difficulty.\n* Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) \\>= 470 ms calculated from 3 electrocardiograms (ECGs) (within 15 minutes at 5 \\[+\u002F- 3\\] minutes apart).\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, evidence of any acute or chronic viral illness or disease, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Pregnant women are excluded from this study because durvalumab (MEDI4736) and tremelimumab has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with durvalumab (MEDI4736) and tremelimumab, breastfeeding should be discontinued if the mother is treated with durvalumab (MEDI4736) and tremelimumab. These potential risks may also apply to other agents used in this study. A negative serum pregnancy test is required no more than 7 days before study entry.\n* Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.\n* History of pneumonitis or interstitial lung disease.\n* History of active primary immunodeficiency.\n* Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and tuberculosis \\[TB\\] testing in line with local practice), hepatitis B (known positive hepatitis B virus \\[HBV\\] surface antigen \\[HBsAg\\] result), or hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \\[anti-HBc\\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).\n* The patient with a previous history of non-breast malignancy is eligible for this study only if the patient meets the following criteria for a cancer survivor. A cancer survivor is eligible provided the following criteria are met:\n\n  * Patient has undergone potentially curative therapy for all prior malignancies.\n  * Patients have been considered disease free for at least 1 year (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).\n* Patients with a strong likelihood of non-adherence (such as difficulties in adhering to follow-up schedule due to geographic distance from the treatment facility) should not be knowingly registered.\n* History of allogeneic organ transplantation.",{"count":293,"type":20},86,[23],"This phase II trial studies how well nab-paclitaxel, durvalumab, and tremelimumab with or without personalized synthetic long peptide vaccine (neoantigen vaccine) works in treating patients with triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. It is not yet known whether giving nab-paclitaxel, durvalumab, and tremelimumab with or without neoantigen vaccine will work better in treating patients with triple negative breast cancer.",[28,297,113],"Invasive Breast Carcinoma","2026-08-07",{"date":257,"type":45},{"date":301,"type":45},"2021-04-13",{"date":303,"type":20},"2026-12-30",{"name":51,"class":52},30,{"id":307,"slug":308,"hasResults":12,"nctId":309,"briefTitle":310,"officialTitle":311,"acronym":4,"eligibilityCriteria":312,"healthyVolunteers":12,"sex":313,"minAge":182,"maxAge":4,"enrollmentInfo":314,"targetDuration":4,"studyType":21,"phases":316,"briefSummary":318,"conditions":319,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":332,"lastUpdatePostDateStruct":333,"startDateStruct":334,"completionDateStruct":336,"leadSponsor":338,"locationsCount":340},"100650009","a-blended-e-health-intervention-to-improve-fear-of-progression-in-women-with-gynecologic-or-breast-cancer-100650009","NCT07741968","A Blended e-Health Intervention to Improve Fear of Progression in Women With Gynecologic or Breast Cancer","An e-Health Intervention for Fear of Progression in Women With Gynecologic or Breast Cancer","Inclusion Criteria:\n\n* Women with stage III or IV GYN (ovarian, endometrial, cervical, vulvar\u002Fvaginal) or breast cancer who are at least 2 months from initial diagnosis OR Women with stage I or II endometrial, ovarian, or breast cancer with carcinosarcoma histology OR Women with stage I or II triple negative breast cancer\n* Score ≥ 34 on the Fear of Progression Short-Form, indicating dysfunctional levels\n* Age 18 or older; able to read and understand English\n* Patients can be on active treatment or surveillance. They can be no evidence of disease (NED), recurrent or with progressive disease\n\nExclusion Criteria:\n\n* Enrolled in hospice\n* Ongoing uncontrolled active psychiatric condition that, in the opinion of the investigator, would interfere in the conduct of the study (e.g., mood disorders, psychosis disorders, or substance use), Major depression as assessed by Patient Health Questionnaire-9 (PHQ-9)\n* Non-English speaking\n* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility\u002Flogistics)\n* Current participation in a mind-body or mindfulness education program within the past six weeks","FEMALE",{"count":315,"type":20},126,[317],"NA","This clinical trial studies whether an intervention supported by technology (blended e-health intervention) works to improve fear of progression (FOP) in women with gynecologic or breast cancer. FOP is the fear patients experience from the possibility that their cancer could grow, spread, or get worse. Managing FOP is a leading unmet concern of cancer patients. High levels of FOP are associated with distress, depression, and increased health care costs, despite this, access to resources to address FOP remain limited. The blended e-health intervention in this trial offers remote group sessions along with online sessions to help patients access the information. Session content incorporates values-based goal setting and skills practices to manage unhelpful beliefs about worry and promote helpful coping behaviors. The sessions may help patients recognize unhelpful thoughts and behaviors which reinforce worry. A blended e-health intervention may be an effective way to improve FOP in women with gynecologic or breast cancer.",[320,321,27,28,322,323,324,30,325,326,116,327,328,132,329,330,145,331],"Anatomic Stage I Breast Cancer AJCC v8","Anatomic Stage II Breast Cancer AJCC v8","Breast Carcinoma","Breast Mixed Epithelial\u002FMesenchymal Metaplastic Carcinoma","Endometrial Carcinoma","Ovarian Carcinoma","Ovarian Carcinosarcoma","Stage III Vaginal Cancer AJCC v8","Stage III Vulvar Cancer AJCC v8","Stage IV Vaginal Cancer AJCC v8","Stage IV Vulvar Cancer AJCC v8","Uterine Corpus Carcinosarcoma","2026-08-06",{"date":257,"type":45},{"date":335,"type":20},"2027-02-22",{"date":337,"type":20},"2028-01-16",{"name":339,"class":173},"City of Hope Medical Center",11,{"id":342,"slug":343,"hasResults":12,"nctId":344,"briefTitle":345,"officialTitle":346,"acronym":4,"eligibilityCriteria":347,"healthyVolunteers":12,"sex":313,"minAge":182,"maxAge":4,"enrollmentInfo":348,"targetDuration":4,"studyType":21,"phases":350,"briefSummary":351,"conditions":352,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":354,"lastUpdatePostDateStruct":355,"startDateStruct":356,"completionDateStruct":358,"leadSponsor":360,"locationsCount":174},"100592927","phase-1-an-optimized-ultrasound-twinkling-marker-for-the-imaging-of-lymph-nodes-in-patients-with-clinically-node-positive-breast-cancer-the-utmost2-trial-100592927","NCT06999798","An Optimized Ultrasound Twinkling Marker for the Imaging of Lymph Nodes in Patients With Clinically Node-Positive Breast Cancer, The UTMOST2 Trial","A Phase 1 Study in Patients With Clinically Node-Positive Breast Cancer to Assess the Safety, Ultrasound Conspicuity, and Migration of an Optimized Ultrasound Twinkling Marker Observed for Sonographic Targeting (UTMOST2 Trial)","Inclusion Criteria:\n\n* Patient 18 years or older with breast cancer and biopsy-proven malignant involvement of an axillary lymph node\n* Surgical management will be determined by the surgeon, who will decide if preoperative Iodine (I)-125 seed localization of the positive node is necessary or if they will retrieve the positive node with intraoperative ultrasound guidance. During surgery, the targeted node, its associated biopsy markers, I-125 seed if placed, and optimized twinkling marker will be resected. The position of the marker in the lymph node or proximity to the node will be noted from the surgical and pathology documentation\n* Surgery will be performed by one of the surgeons in the Division of Breast and Melanoma Surgical Oncology (Doctor \\[Dr.\\] Judy Boughey, Dr. Amy Degnim, Dr. Tina Hieken, Dr. Jeffrey Johnson, Dr. Mary Mrdutt, Dr. Shon Black)\n* Patients must be able to understand the study procedures and comply with them for the entire length of the study\n* No contraception is necessary or required\n\nExclusion Criteria:\n\n* Patients who are pregnant\n* Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements\n* Current or past participation within a specified timeframe in another clinical trial, as warranted by the administration of this intervention",{"count":349,"type":20},20,[66],"This phase I trial studies the performance, including ultrasound visibility, of an optimized ultrasound twinkling marker in imaging lymph nodes in patients with clinically node-positive breast cancer. In patients with biopsy-proven breast cancer, biopsy markers are used to identify the sites of cancer involvement in both the breasts and lymph nodes. These biopsy markers are critical for guiding surgical management many months after the marker is placed. For breast radiologists and breast surgeons, there is a need for simple, consistent visibility of biopsy markers by ultrasound, particularly several months after marker placement. Ultrasound is the imaging method of choice, particularly for lymph nodes in the armpit (axilla). Ultrasound is non-ionizing and is more comfortable for patients compared to mammography. However, ultrasound visibility of these markers is challenging and inconsistent, with ultrasound failing to detect the marker approximately 25% of the time. The Mayo-designed investigational biopsy marker takes advantage of an ultrasound phenomenon called twinkling artifact. The Mayo-designed optimized ultrasound twinkling marker may work better than standard biopsy clip marker in imaging lymph nodes in patients with clinically node-positive breast cancer.",[321,27,28,353],"Locally Advanced Breast Carcinoma","2026-08-04",{"date":332,"type":45},{"date":357,"type":45},"2025-08-29",{"date":359,"type":20},"2026-11-30",{"name":172,"class":173},{"id":362,"slug":363,"hasResults":12,"nctId":364,"briefTitle":365,"officialTitle":366,"acronym":4,"eligibilityCriteria":367,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":368,"targetDuration":4,"studyType":21,"phases":370,"briefSummary":371,"conditions":372,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":373,"lastUpdatePostDateStruct":374,"startDateStruct":376,"completionDateStruct":378,"leadSponsor":380,"locationsCount":174},"100463728","phase-1-ivermectin-in-combination-with-balstilimab-or-pembrolizumab-in-patients-with-metastatic-triple-negative-breast-cancer-100463728","NCT05318469","Ivermectin in Combination With Balstilimab or Pembrolizumab in Patients With Metastatic Triple Negative Breast Cancer","A Phase I\u002FII Study Evaluating the Safety and Efficacy of Ivermectin in Combination With Immune Checkpoint Inhibitor in Patients With Metastatic Triple Negative Breast Cancer","Inclusion Criteria:\n\n* Age: ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) ≤ 1\n* Life expectancy \\> 3 months\n* Histologically confirmed metastatic triple negative breast cancer. Triple negative status will be defined as estrogen receptor (ER) and progesterone receptor (PR) ≤ 10% and HER2 negative (by immunohistochemistry \\[IHC\\] or fluorescence in situ hybridization \\[FISH\\]), per American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guidelines\n* Patients must have progressed on 1-2 prior lines of systemic therapy (chemotherapy and\u002For drug-antibody conjugate) in the metastatic setting\n* Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions\n* Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 2 from prior anti-cancer therapy\n* For Phase 2 expansion only, must be PD-L1 negative. Note: For Phase 1 safety cohort, any PD-L1 status will be allowed to enroll.\n* Patients must have adequate organ function as defined in the following:\n* Absolute neutrophil count (ANC) ≥ 1,500\u002Fmm\\^3\n* Platelets ≥ 100,000\u002Fmm\\^3\n* Hemoglobin ≥ 9.0 g\u002FdL or ≥ 5.6 mmol\u002FL. Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks\n* Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \\> 1.5 x ULN\n* Aspartate aminotransferase (AST) ≤ 1.5 x ULN or ≤ 3 x ULN with liver metastases\n* Alanine aminotransferase (ALT) ≤ 1.5 x ULN or ≤ 3 x ULN with liver metastases\n* Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance ≥ 30 mL\u002Fmin for participant with creatinine levels \\>1.5 x institutional ULN\n* International normalized ratio (INR) or prothrombin time (PT), activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants\n* Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram\n* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test\n\n  * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* A male participant must agree to use a contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period\n* A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:\n\n  * Not a woman of childbearing potential (WOCBP) OR\n  * Females of child-bearing potential must be willing to use effective contraception during study and for 120 days after the last dose\n* Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.\n\nExclusion Criteria:\n\n* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug\n* Prohibited Treatments and\u002For Therapies:\n* Chemotherapy, radiation therapy, biological therapy, immunotherapy within 28 days prior to day 1 of protocol therapy\n* Prior immune checkpoint inhibitor therapy in metastatic setting (Note: Prior use of immune checkpoint inhibitor in neoadjuvant or adjuvant setting only permitted if last dose is at least 1 year from start of study intervention)\n* Prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease\n* Any live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella\u002Fzoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed\n* Participants on any dose of warfarin. Use of low molecular weight heparin, antithrombin agents, anti-platelet agents or factor Xa inhibitors is allowed\n* Participants may not be currently participating in or participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention\n* Issues with tolerating oral medication (e.g., inability to swallow pills, malabsorption issues, ongoing nausea or vomiting during screening)\n* Women who are or are planning to become pregnant or breastfeed\n* Known allergy to any of the components within the study agents and\u002For their excipients\n* No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least three years\n* Participants must not have known active CNS metastases and\u002For carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention\n* History of (non-infectious) pneumonitis that required steroids or has current pneumonitis\n* Active infection requiring systemic therapy\n* Known history of Human Immunodeficiency Virus (HIV) infection\n* Known history of Hepatitis B (defined as Hepatitis B surface antigen \\[HBsAg\\] reactive) or known active Hepatitis C virus (defined as HCV RNA \\[qualitative\\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority\n* Known history of active TB (Mycobacterium tuberculosis)\n* Intercurrent or historic medical condition that increases subject risk in the opinion of the Investigator. Eligibility may be revisited for intercurrent medical conditions once resolution\u002Frecovery is deemed adequate by the investigator (e.g., recovery from major surgery, completion of treatment for severe infection).\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator\n* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial\n* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment\n* Has had an allogenic tissue\u002Fsolid organ transplant\n* Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) class II, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at screening\n* Subjects having \\> 1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is \\\u003C 1 g\u002F24 hours\n* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed\n* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures",{"count":369,"type":20},34,[66,23],"This phase II trial studies the side effects and best dose of ivermectin in combination with balstilimab or pembrolizumab and to see how well they they work in shrinking tumors in patients with triple negative breast cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as balstilimab or pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ivermectin may help block the formation of growths that may become cancer. Giving ivermectin with balstilimab or pembrolizumab may increase the effect of balstilimab or pembrolizumab in shrinking tumors in patients with triple negative breast cancer. The secondary objectives of the study include evaluating the following efficacy outcomes: objective response rate (ORR), progression free survival (PFS), overall survival (OS), duration of response (DOR), clinical benefit rate (CBR), and patients' quality of life (QOL) by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).",[28,113],"2026-08-03",{"date":375,"type":45},"2026-08-05",{"date":377,"type":45},"2023-10-13",{"date":379,"type":20},"2026-10",{"name":381,"class":173},"Yuan Yuan",{"id":383,"slug":384,"hasResults":12,"nctId":385,"briefTitle":386,"officialTitle":387,"acronym":4,"eligibilityCriteria":388,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":389,"targetDuration":4,"studyType":21,"phases":390,"briefSummary":391,"conditions":392,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":393,"lastUpdatePostDateStruct":394,"startDateStruct":395,"completionDateStruct":397,"leadSponsor":399,"locationsCount":174},"100598985","phase-2-a-cancer-vaccine-stemvac-in-combination-with-chemotherapy-for-the-treatment-of-pd-l1-negative-metastatic-triple-negative-breast-cancer-100598985","NCT07078604","A Cancer Vaccine (STEMVAC) in Combination With Chemotherapy for the Treatment of PD-L1 Negative Metastatic Triple-Negative Breast Cancer","A Phase II Trial of the Immunogenicity of a DNA Plasmid-Based Vaccine (STEMVAC) Encoding Th1 Selective Epitopes From Five Antigens Associated With Breast Cancer Stem Cells (MDM2, YB1, SOX2, CDH3, CD105) in Patients With Metastatic Triple-Negative Breast Cancer","Inclusion Criteria:\n\n* Patients must be at least ≥ 18 years of age\n\n  * Note: Because no dosing or adverse event (AE) data are currently available on the use of STEMVAC in patients \\\u003C 18 years of age, children and adolescents are excluded from this study, but will be eligible for future pediatric trials, if applicable\n* Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status Score of ≤ 2\n* Histologically confirmed triple-negative breast cancer\n\n  * Tumors with estrogen receptor (ER)-low (≤ 5%) or negative and progesterone receptor (PR)-low (≤ 5%) or negative will be included\n  * HER2-negative or HER2-low will be defined by the American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) 2023 \"Human Epidermal Growth Factor Receptor 2 (HER2) Breast Testing Guideline Update\" which reaffirms the 2018 \"HER2 Breast Testing Guideline Focused Update\"\n* Tumor is negative for PD-L1 marker testing per standard of care immunohistochemistry 22C3 pharmDx assay\n* Metastatic disease that is measurable based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions\n* Have at least 1 site of disease confirmed by the treating oncologist that could be biopsied during treatment. Lesions that will be biopsied should not be in a previously irradiated area unless progression has been demonstrated in such lesions\n* Patients can not have received any prior cancer immunotherapy in the metastatic setting\n* Prior Food and Drug Administration (FDA)-approved antibody drug conjugates are allowed\n* Patients are appropriate candidates to receive standard of care chemotherapy as per treating oncologist's clinical judgement\n* Patients who have received prior neoadjuvant or adjuvant chemotherapy are allowed\n* A minimum of 14 days washout since last systemic therapy or any palliative radiotherapy is required\n* Treatment with a bisphosphate or denosumab concurrently with protocol-specific therapy is allowed while on study (it is not exclusionary)\n* Patients must be at least 28 days post systemic steroids prior to enrollment, unless this is a steroid administered concurrently with chemotherapy or used as part of prophylaxis to prevent intravenous (IV) contrast reactions\n* Must have recovered from major infections and\u002For surgical procedures; and in the opinion of the investigator, not have any significant active concurrent medical illnesses or condition precluding protocol treatment\n* Willing to undergo up to two serial biopsies while on study\n* White blood cell (WBC) ≥ 2.5 THOU\u002FuL (Within 28 days of receiving first study vaccine)\n* Lymphocyte count ≥ 0.5 THOU\u002FuL (Within 28 days of receiving first study vaccine)\n* Absolute neutrophil count (ANC) ≥ 1.0 THOU\u002FuL (Within 28 days of receiving first study vaccine)\n* Hemoglobin (Hgb) ≥ 9 g\u002FdL (Within 28 days of receiving first study vaccine)\n* Platelets ≥ 75 THOU\u002FuL (Within 28 days of receiving first study vaccine)\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert's syndrome in whom total bilirubin must be \\\u003C 3.0 mg\u002Fd (Within 28 days of receiving first study vaccine)\n* Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) ≤ 1.5 x institutional ULN (Within 28 days of receiving first study vaccine)\n* Creatinine ≤ 1.5 x ULN mg\u002FdL or creatinine clearance \\> 60 mL\u002Fmin (Within 28 days of receiving first study vaccine)\n* Patients of child-bearing potential must agree to use dual methods of contraception and have a negative urine pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a person of child-bearing potential. Acceptable methods of contraception are abstinence, condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. Effective methods of contraception must be used throughout the study until the end of treatment on study\n\nExclusion Criteria:\n\n* Patient has received more than one line of prior therapy in metastatic setting\n* Patients with tumors that are PD-L1-positive per standard of care immunohistochemistry 22C3 pharmDx assay\n* Enrollment in a concurrent interventional clinical trial. Biomarker or tissue collection or any other non-interventional clinical trial enrollment is allowed. Participation in a trial for chimeric antigen receptor (CAR)-T cell therapy may be permitted if the CAR-T cell therapy is not planned to occur until after the currently proposed treatment (i.e. no longer participating in STEMVAC and chemotherapy trial)\n* Patients with any of the following cardiac conditions:\n\n  * Symptomatic restrictive cardiomyopathy\n  * Dilated cardiomyopathy\n  * Unstable angina within 4 months prior to enrollment\n  * New York Heart Association functional class III-IV heart failure on active treatment\n  * Symptomatic pericardial effusion\n* Patients with any autoimmune disease or comorbidities that require chronic systemic steroids or immunosuppressants. Patients with conditions requiring inhaled, intranasal or topical steroids are permitted\n* Known hypersensitivity reaction to the granulocyte-macrophage colony stimulating factor (GM-CSF) adjuvant; any known contra-indication to GM-CSF\n* A non-breast malignancy requiring radiation or systemic therapy within last 5 years or any B-cell malignancy (e.g., chronic lymphocytic leukemia or follicular lymphoma) under active surveillance\n* Pregnant and breastfeeding individuals\n* Known history of human immunodeficiency virus (HIV) infection, hepatitis B (e.g., hepatitis B virus surface antigen \\[HBsAg\\] reactive), or hepatitis C (e.g., hepatitis C virus \\[HCV\\] ribonucleic acid \\[RNA\\] \\[qualitative\\] is detected)\n* Major surgery within the 4 weeks prior to initiation of study vaccine\n* Must be 14 days between a non-study vaccine, including live attenuated and non-live vaccines and any STEMVAC vaccination\n\n  * Note: The minimum of 14 days does not apply to the tetanus and diphtheria (Td) vaccine\n* Any condition that may interfere with the patient's participation in the study per treating physician",{"count":349,"type":20},[23],"This phase II trial studies how well a cancer vaccine called STEMVAC works in combination with chemotherapy in treating patients with PD-L1 negative, triple-negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). STEMVAC is designed to target proteins that are expressed on breast cancer stem cells, and it is believed to work by boosting the immune system to recognize and destroy the invader tumor cells that are causing the disease. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving STEMVAC in combination with chemotherapy may be an effective treatment for PD-L1 negative metastatic triple-negative breast cancer.",[28,113],"2026-07-31",{"date":354,"type":45},{"date":396,"type":45},"2026-03-24",{"date":398,"type":20},"2028-06-30",{"name":241,"class":173},{"id":401,"slug":402,"hasResults":12,"nctId":403,"briefTitle":404,"officialTitle":405,"acronym":4,"eligibilityCriteria":406,"healthyVolunteers":12,"sex":17,"minAge":407,"maxAge":4,"enrollmentInfo":408,"targetDuration":4,"studyType":21,"phases":410,"briefSummary":411,"conditions":412,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":416,"lastUpdatePostDateStruct":417,"startDateStruct":418,"completionDateStruct":420,"leadSponsor":422,"locationsCount":423},"100467889","phase-1-testing-the-safety-and-efficacy-of-the-combination-of-two-anti-cancer-drugs-zen003694-and-abemaciclib-for-adult-and-pediatric-patients-12-17-years-with-metastatic-or-unresectable-nut-carcinoma-breast-cancer-and-other-solid-tumors-100467889","NCT05372640","Testing the Safety and Efficacy of the Combination of Two Anti-cancer Drugs, ZEN003694 and Abemaciclib, for Adult and Pediatric Patients (12-17 Years) With Metastatic or Unresectable NUT Carcinoma, Breast Cancer and Other Solid Tumors","A Phase 1 Study of BET Bromodomain Inhibitor ZEN003694 in Combination With the CDK4\u002F6 Inhibitor Abemaciclib in Patients With NUT Carcinoma, Breast Cancer and Other Solid Tumors","Inclusion Criteria:\n\n* Participants must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective\n* Dose Escalation Cohort Only: Participants must have evaluable disease or measurable disease per RECIST 1.1 criteria\n* Dose Expansion Cohort Only:\n\n  * Participants must have a diagnosis of NUT carcinoma (NC) based on standard criteria for the disease, with diagnostic testing performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory:\n\n    * Ectopic expression of NUT protein per World Health Organization (WHO) criteria as determined by immunohistochemistry (IHC) testing, OR\n    * Detection of the NUT gene translocation as determined by fluorescence in situ hybridization (FISH) testing, OR\n    * Detection of the NUT gene translocation as determined by either deoxyribonucleic acid (DNA) next-generation sequencing (NGS) or ribonucleic acid (RNA) sequencing.\n  * Participants must have measurable disease per RECIST 1.1 criteria\n* Any number of prior lines of therapy in the metastatic setting are allowed, including prior BET inhibitor therapy and prior CDK4\u002F6 inhibitor therapy\n* Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \\[CTCAE\\] grade =\\\u003C 1) from the acute effects of chemotherapy except for residual alopecia or grade 2 peripheral neuropathy\n* Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy\n* Participants may have previously undergone surgical resection\n* Age \\>= 12 years. Patients 12-17 years of age must be \\> 40 kg at enrollment. Patients 12-17 years of age will not participate in the mandatory tumor biopsies. Since there is no data on patients less than 18 years of age, this population may require lower doses and additional safety precautions and should be closely monitored. Because no dosing or adverse event data are currently available on the use of ZEN003694 in combination with abemaciclib in patients \\\u003C 12 years of age, younger children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2 for participants \\>= 16 years of age, Lansky \\>= 50% if \\\u003C 16 years of age\n* Hemoglobin \\>= 8 g\u002FdL; Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion\n* Absolute neutrophil count \\>= 1.5 x 10\\^9\u002FL\n* Platelets \\>= 1 x 10\\^11\u002FL\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN) for age. Patients with Gilbert's syndrome with a total bilirubin =\\\u003C 2.0 times ULN and direct bilirubin within normal limits are permitted\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\\u003C 2.5 x institutional ULN for age\n* Serum or plasma creatinine =\\\u003C 1.5 x institutional ULN OR calculated creatinine clearance \\>= 50 mL\u002Fmin (via the chronic kidney disease epidemiology \\[CKD-EPI\\] glomerular filtration rate estimation) for participants \\>= 18 years old, or 60 mL\u002Fmin\u002F1.73m\\^2 for patients 12-17 years as calculated based on bedside Schwartz formula\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Hepatitis C (HepC antibody) testing is required. Hepatitis C RNA is optional; however, a confirmatory negative Hepatitis C RNA test must be obtained to be able to enroll participants with positive Hepatitis C antibody due to prior resolved disease\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression and has been clinically stable for at least 1 month. Patients must meet the following criteria:\n\n  * Disease outside the CNS is present\n  * Recovery from acute toxicity associated with the treatment to =\\\u003C CTCAE grade 1 or baseline (with the exception of alopecia), with no requirement for escalating doses of corticosteroids over the past 7 days\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients should be New York Heart Association Functional Classification of class 2B or better\n* Ability to swallow and retain oral medications\n* The effects of ZEN00364 and abemaciclib on the developing human fetus are unknown. For this reason and because BETi and CDKi-inhibiting agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of child-bearing potential must have a negative pregnancy test prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 weeks after completion of ZEN003694 and abemaciclib administration\n\n  * For female subjects of child-bearing potentially receiving ZEN003694, hormonal means of birth control alone, such as oral, injectable, dermal, subdermal or topical contraceptives are NOT acceptable forms of birth control given that their efficacy has not been evaluated when given in combination with the investigational drugs. \"Adequate contraception\" is defined as the following:\n\n    * Contraceptive methods with a failure rate of =\\\u003C 1% used in combination with the barrier method. The following contraceptive methods are acceptable to use in combination with the barrier method: intrauterine device (IUD), intrauterine system (IUS), or oral contraceptive pills (OCPs) that meet the \\\u003C 1% failure rate as stated in the product label. Note: Hormonal IUDs\u002FOCPs may only be used if the following criteria are met: male condoms are required AND subjects are informed of the potential for reduced systemic hormone levels from the IUD\u002FOCP when taking ZEN003694. Alternatively, male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, \"documented\" refers to the outcome of the investigator's\u002Fdesignee's medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records\n  * Male subjects with female partners of child-bearing potential must use one of the following contraceptive methods:\n\n    * Vasectomy with documentation of azoospermia OR\n    * Condom use PLUS partner use of a highly effective contraceptive (=\\\u003C 1% rate of failure per year) such as intrauterine device or system, or hormonal birth control such as contraceptive subdermal implant, combined estrogen and progestogen oral contraceptive, injectable progestogen, contraceptive vaginal ring, or percutaneous contraceptive patches\n  * Male subjects should not donate sperm while on study and for 12 weeks after the last dose of study medication. Male subjects whose partners are or become pregnant must continue to use condoms for 12 weeks after the last dose of study medication\n* Women of childbearing potential must have a negative pregnancy test within 7 days of starting treatment\n* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and\u002For family member available may be eligible after discussion with the Principal Investigator of this study. There will be a separate assent process for minors\n\nExclusion Criteria:\n\n* Participants who have had cytotoxic chemotherapy, immunotherapy, or other investigational therapy within 2 weeks prior to entering the study. There is a two-week required washout period for previous BET inhibitor therapy\n* Participants who have had radiotherapy within at least 2 weeks prior to entering the study. Stereotactic radiosurgery (SRS) within 1 week prior to entering the study will be allowed\n* Participants who have had major surgery within 3 weeks prior to entering the study\n* Participants who have received tyrosine kinase inhibitors (TKIs) or small molecules within 5 half-lives or 1 week (whichever is shorter) of study entry\n* Patients who are receiving any other investigational agents\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 or abemaciclib\n* Patients requiring medications or substances that are strong inhibitors or strong inducers of CYP3A4 or CYP3A enzymes are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694 and abemaciclib. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http:\u002F\u002Fmedicine.iupui.edu\u002Fclinpharm\u002Fddis\u002Ftable.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* Patients with uncontrolled intercurrent illness, including but not limited to: ongoing or active infection requiring systemic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment (e.g. estimated creatinine clearance \\\u003C 30ml\u002Fmin), history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea that, in the judgment of the investigator, would preclude participation in this study\n* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694. As proton pump inhibitors (PPIs), H2 receptor antagonists, and antacids may alter the pharmacokinetics of ZEN003694 by reducing ZEN003694 exposure, patients receiving proton pump inhibitors are ineligible. If H2 blockers or other acid reducing agents are used concomitantly with ZEN003694, a staggered dosing schedule should be used. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* Pregnant women are excluded from this study because ZEN003694 is a BETi agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694, breastfeeding should be discontinued if the mother is treated with ZEN003694. These potential risks may also apply to other agents used in this study\n* Fridericia's formula-corrected QT interval (QTcF) \\>= 450 msec on screening electrocardiogram (ECG) by Fredericia (machine or manual read allowed). Patients should avoid medications which prolong the QT\n* Patients receiving any medications or substances that are Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) or Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed\n* Patients with radiation to \\> 25% of the bone marrow\n* Patients who have had a bone-targeted radionuclide within 6 weeks of the first dose of ZEN003694\n* Myocardial infarction or unstable angina within 6 months prior to the first dose of ZEN003694\n* Impairment of gastrointestinal function that may significantly alter the absorption of ZEN003694 and\u002For abemaciclib\n* The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest","12 Years",{"count":409,"type":20},45,[66],"This phase I trial tests the safety, side effects, and best dose of ZEN003694 when given together with abemaciclib in treating patients with NUT carcinoma, breast cancer or other solid tumors that have spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that overproduce BET protein. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ZEN003694 and abemaciclib may help shrink or stabilize cancer in patients with NUT carcinoma, breast cancer or other solid tumors.",[27,28,189,32,413,414,40,415],"Metastatic NUT Carcinoma","Unresectable Breast Carcinoma","Unresectable NUT Carcinoma","2026-07-30",{"date":393,"type":45},{"date":419,"type":45},"2023-08-10",{"date":421,"type":20},"2027-06-07",{"name":51,"class":52},7,{"id":425,"slug":426,"hasResults":12,"nctId":427,"briefTitle":428,"officialTitle":429,"acronym":4,"eligibilityCriteria":430,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":431,"targetDuration":4,"studyType":21,"phases":433,"briefSummary":434,"conditions":435,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":416,"lastUpdatePostDateStruct":439,"startDateStruct":440,"completionDateStruct":442,"leadSponsor":444,"locationsCount":174},"100402553","phase-1-a-vaccine-mv-s-nap-for-the-treatment-of-patients-with-invasive-metastatic-breast-cancer-100402553","NCT04521764","A Vaccine (MV-s-NAP) for the Treatment of Patients With Invasive Metastatic Breast Cancer","Phase I Trial of Intratumoral Administration of a Measles Virus Derivative Expressing the Helicobacter Pylori Neutrophil-Activating Protein (NAP) (MV-s-NAP) in Patients With Metastatic Breast Cancer","Inclusion Criteria:\n\n* Age \\>= 18 years\n* COHORT 1 ONLY: Pathologically confirmed invasive breast adenocarcinoma with documented estrogen receptor (ER)\u002Fprogesterone receptor (PR) \u002FHER2 status and radiographic evidence of distant metastatic disease\n* COHORTS 2 \\& 3 ONLY: Pathologically confirmed invasive breast adenocarcinoma with documented ER\u002FPR\u002FHER2 status and radiographic evidence of distant metastatic or recurrent disease\n* COHORT 1 ONLY: Radiographic evidence of distant metastatic disease (using 7th edition American Joint Committee on Cancer \\[AJCC\\] criteria) with two discrete sites of measurable disease\n* COHORTS 2 \\& 3 ONLY: Radiographic evidence of distant metastatic or recurrent disease (using 8th edition AJCC criteria) with at least one site of measurable disease\n* Prior therapies:\n\n  * Patients with ER\u002FPR positive, HER2 negative breast cancer must have progressed through at least one prior cytotoxic regimen for advanced disease and no longer be candidates for standard endocrine therapy or combination of endocrine therapy with other agents such as CDK4\u002F6 inhibitors\n  * Patients with HER2 positive breast cancer irrespective of ER\u002FPR status must have received or no longer be candidates for HER2 directed therapy with trastuzumab or pertuzumab\n  * Patients with ER\u002FPR\u002FHER2 negative breast cancer must have progressed through at least one prior cytotoxic regimen for advanced disease\n* COHORT 1: At least one site of recurrent\u002Fmetastatic disease that measures \\> 1 cm in greatest dimension (\\> 2 cm for lung lesions) and is amenable to safe percutaneous intratumoral administration of MV-s-NAP as determined by an interventional radiologist\n* COHORTS 2 \\& 3 ONLY: At least 1 site of recurrent\u002Fmetastatic disease measuring \\> 1 cm in greatest dimension \\[\\> 2 cm for lung lesions\\] (Note that if the lesion injected in cycle 1 is not amenable to re-injection, another lesion could be selected for injection\n* Absolute neutrophil count (ANC) \\>= 1500\u002FuL (=\\\u003C 7 days prior to registration)\n* Platelets (PLT \\>= 100,000\u002FuL) (=\\\u003C 7 days prior to registration)\n* Total bilirubin =\\\u003C institutional upper limit of normal (=\\\u003C 7 days prior to registration)\n* Aspartate aminotransferase (AST) =\\\u003C 2 x upper limit of normal (ULN) (=\\\u003C 7 days prior to registration)\n* Creatinine =\\\u003C 1.5 x ULN (=\\\u003C 7 days prior to registration)\n* Hemoglobin \\>= 9.0 g\u002FdL (=\\\u003C 7 days prior to registration)\n* Negative pregnancy test done =\\\u003C 7 days prior to registration (for women of childbearing potential only)\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2\n* Ability to provide informed written consent\n* Willingness to return to the Mayo Clinic enrolling institution for follow-up\n* Willingness to provide biologic samples for correlative research purposes\n* Life expectancy \\>= 12 weeks\n* Concomitant administration of a bone modifying agent (e.g., zoledronic acid or denosumab) is permitted for the prevention or management of skeletal related events in patients with bone metastases and documentation of tolerability with prior exposures\n\nExclusion Criteria:\n\n* Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy\n* Clinical or radiographic suspicion of impending visceral crisis due to invasion or compression by tumor\n* Active infection =\\\u003C 5 days prior to registration\n* History of other malignancy =\\\u003C 5 years except for non-melanoma skin cancer or carcinoma in situ of the cervix\n* Any of the following prior therapies:\n\n  * Chemotherapy =\\\u003C 3 weeks prior to registration\n  * Immunotherapy =\\\u003C 4 weeks prior to registration\n  * HER2 directed therapy =\\\u003C 3 weeks prior to registration\n  * Targeted therapy =\\\u003C 2 weeks prior to registration (e.g., CDK4\u002F6 inhibitors, everolimus)\n  * Investigational agent =\\\u003C 4 weeks prior to registration\n  * Any viral or gene therapy prior to registration\n* Failure to fully recover from acute, reversible effects of prior systemic therapy regardless of interval since last treatment\n* New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias (atrial fibrillation or supraventricular tachycardia \\[SVT\\])\n* Untreated or progressive central nervous system (CNS) metastases\n\n  * NOTE: Patients with a history of treated brain metastases (surgical resection, whole brain radiation, and\u002For stereotactic radiosurgery) are eligible only if they are asymptomatic and have stable MRI scans for 3 consecutive months, including \\\u003C 28 days of study entry\n* Standing requirement for blood product support\n* Human immunodeficiency virus (HIV) positive test result or history of other immunodeficiency\n* History of organ transplantation\n* History of chronic hepatitis B or C\n* Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration \\[FDA\\]-approved indication and in the context of a research investigation)\n* Any concurrent medications that the principal investigator determines could interfere with the trial\n* Treatment with oral\u002Fsystemic corticosteroids, with the exception of topical or inhaled steroids or low dose systemic steroids for physiologic replacement (e.g., Prednisone ≤10 mg\u002Fday)\n* Exposure to household contacts =\\\u003C 15 months old or household contact with known immunodeficiency\n* Allergy to measles vaccine or history of severe reaction to prior measles vaccination\n* History of receiving the measles vaccination with the \"killed vaccine\" between 1963-1967 without subsequent re-immunization (2 doses) with the active, live vaccination.\"",{"count":432,"type":20},54,[66],"This phase I trial investigates the side effects and best dose of using a modified measles virus, MV-s-NAP, in treating patients with invasive breast cancer that has spread to other places in the body (metastatic). Both the unmodified vaccination measles virus (MV-Edm) and this modified virus (MV-s-NAP) have been shown to multiply in and destroy breast cancer cells in the test tube and in research mice. MV-s-NAP has been altered by having an extra gene (piece of deoxyribonucleic acid \\[DNA\\]) so that virus can make a protein called helicobacter pylori neutrophil activating protein (NAP) which is normally expressed in inflammatory reactions. Monitoring blood, urine, tissue, and throat swab samples, and using imaging tests may help to determine whether MV-s-NAP has any impact on the amount of disease present in metastatic breast cancer patients.",[28,297,436,437,438],"Metastatic Breast Adenocarcinoma","Recurrent Breast Carcinoma","Stage IV Breast Cancer AJCC v6 and v7",{"date":393,"type":45},{"date":441,"type":45},"2020-09-23",{"date":443,"type":20},"2027-08-15",{"name":172,"class":173},{"id":446,"slug":447,"hasResults":12,"nctId":448,"briefTitle":449,"officialTitle":450,"acronym":4,"eligibilityCriteria":451,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":452,"targetDuration":4,"studyType":21,"phases":454,"briefSummary":455,"conditions":456,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":458,"lastUpdatePostDateStruct":459,"startDateStruct":461,"completionDateStruct":463,"leadSponsor":465,"locationsCount":174},"100518139","phase-1-gemcitabine-and-ex-vivo-expanded-allogenic-universal-donor-tgfi-natural-killer-nk-cells-with-or-without-naxitamab-danyelza-for-the-treatment-of-patients-with-metastatic-gd2-expressing-her2-negative-breast-cancer-100518139","NCT06026657","Gemcitabine and Ex Vivo Expanded Allogenic Universal Donor, TGFβi Natural Killer (NK) Cells With or Without Naxitamab (Danyelza) for the Treatment of Patients With Metastatic, GD2 Expressing, HER2 Negative Breast Cancer","Phase 1b\u002F2 Study of Naxitamab (Danyelza), Gemcitabine and Ex Vivo Expanded Allogenic Universal Donor, TGFβi Natural Killer (NK) Cells in Advanced GD2-expressing Breast Cancers (DiG NKs)","Inclusion Criteria:\n\n* Patients must have histologically or cytologically confirmed, HER2 negative metastatic breast cancer that is historically GD2 expressing (e.g., triple negative breast cancer, metaplastic breast cancer, high grade 3 estrogen positive breast cancer at initial diagnosis) with available archival tissue. Well differentiated neuroendocrine tumor (NETs) are not eligible for this trial since GD2 expression is unknown. GD2 expression is not required for eligibility but a primary tumor paraffin block is required at enrollment for assessment of GD2 expression\n* Patients must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for the evaluation of measurable disease\n* Patients must have received at least one prior treatment for metastatic disease and progressed on treatment or been intolerant to treatment\n* Female or male \\>=18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1\n* Absolute neutrophil count \\>= 1,500\u002FmcL (\\> 1.5 X 10\\^6\u002FL)\n* Platelets \\>= 100,000\u002FmcL\n* Hemoglobin \\>= 9 mg\u002FdL (transfusion to obtain hemoglobin \\>= 9 mg\u002FdL within 24 hours prior to dosing is allowed)\n* Serum creatinine =\\\u003C 1.5 X upper limit of normal (ULN) or measured or calculated creatinine clearance (CrCl) \\>= 60 mL\u002Fmin for participant with creatinine levels \\> 1.5 X institutional upper limit of normal (ULN) (Glomerular filtration rate \\[GFR\\] can also be used in place of creatinine or CrCl)\n* Patients must have adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =\\\u003C 3 X ULN and total bilirubin \\\u003C 1.5 X ULN, unless known diagnosis of Gilbert's syndrome, where bilirubin =\\\u003C 5 mg\u002FdL will be permitted. Gilbert's syndrome will be defined as elevated unconjugated bilirubin, with conjugated (direct) bilirubin within the normal range and less than 20% of the total. Total bilirubin will be permitted up to 5 mg\u002FdL, if patients have historical readings consistent with the definition of Gilbert's syndrome prior to entering study. Adequate hepatic function for patients with known liver metastases is defined as AST and ALT levels ≤ 5 X ULN\n* The effects of the trial agents on the developing human fetus are unknown. However, gemcitabine is known to have negative fetal effects. For this reason: Women of childbearing potential must agree to use adequate contraception at study entry, for the duration of study participation and for 7 months after the last dose of study medication based upon estimated half-life or receptor occupancy. Adequate contraception is defined as 2 highly effective methods of contraception (including a physical barrier). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men should refrain from fathering a child using adequate contraception or donating sperm during the study and for 6 months after the last dose of study medications. Adequate contraception is defined as 2 highly effective methods of contraception (including a physical barrier)\n* Patients with well-controlled human immunodeficiency virus (HIV) infection are eligible for trial as long as:\n\n  * On an effective anti-retroviral therapy (ART) ˃ 4 weeks and with evidence of viral-suppression as defined as HIV viral load ˂ 400 copies\u002FmL within the last 3 months\n  * CD4 \\> 200 cells\u002FµL within the last 3 months; and\n  * No reported opportunistic infections within 6 months prior to enrollment, except for the following which will be allowed:\n\n    * Esophageal candidiasis treated within last 6 months or currently improving with antifungal treatment.\n    * Oral and\u002For genital herpes simplex virus (HSV) treated within last 6 months or currently improving with antiviral treatment.\n    * Mycobacterium avium infection in last 6 months or that has been treated for at least 1 month\n* Patients with evidence of chronic hepatitis B virus (HBV) infection are eligible for trial as long as the HBV viral load is undetectable on suppressive therapy, if indicated.\n\n  * Patients with history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable or unquantifiable HCV ribonucleic acid (RNA) 12 weeks or longer after definitive treatment completion.\n  * Patients must be able to understand and willing to sign a written informed consent document\n* Any adverse events subjects have experienced from prior therapy must have resolved to =\\\u003C grade 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5\n\nExclusion Criteria:\n\n* Patients who within 3 weeks prior to study enrollment who have received chemotherapy, investigational agents, or radiation\n* Patients with active brain metastases or leptomeningeal metastases are excluded from this clinical trial because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients with treated brain metastases are eligible if there is no magnetic resonance imaging (MRI) evidence of progression for 6 months after treatment is complete and within 28 days prior to the first dose of trial drug. Patients requiring immunosuppressive doses of systemic corticosteroids (\\> 10mg\u002Fday prednisone equivalent) for palliation are excluded\n* Patients with a history of another invasive malignancy \\\u003C 3 years prior to enrollment (patients with non-melanoma skin cancers, carcinoma in situ of the breast or cervix are eligible)\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study\n* Uncontrolled intercurrent illness including, but not limited to, ongoing active infection that requires systemic treatment with ongoing antibiotics (eligible if can stop antibiotics on day of enrollment), unexplained fever (temperature \\> 38.1˚celcius \\[C\\]) within 7 days of initial treatment, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situation that in the opinion of the primary investigator would prohibit the patient from complying with study requirements\n* Patients with bone metastases who have initiated denosumab or a bisphosphonate therapy within 28 days prior to or after cycle 1 day 1 due to the potential for flu-like symptoms and mild cytokine release syndrome with the initial dose. However, continuation of prior therapy is allowed\n* Patients should have no evidence of being immunocompromised as listed below:\n\n  * Active, known or suspected autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to an autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger in the opinion of the primary investigator\n  * Altered immune function that in the judgement of the PI that may affect a patient's ability to adequately engage the immune system and respond to the immunotherapy agents being administered, including but not limited to: inflammatory bowel disease; active infectious enteritis; eosinophilic enteritis; lupus erythematous; ankylosing spondylitis; scleroderma; multiple sclerosis. These criteria do not include all disease with an immune-related component but are not autoimmune in nature or have a primary alteration in the general immune function that may interfere with the vaccine mechanism of action, for example celiac disease\n  * Immunosuppressive therapy post-organ transplant\n  * Concurrent use of chronic use of systemic steroids, except for physiologic doses of systemic steroids for replacement, defined as 10mg of prednisone per day or equivalent, or local (topical, nasal, ophthalmic or inhaled) steroid use or prior concomitant use with chemotherapy. Systemic steroids must have been discontinued \\>2 weeks prior to trial start. Prior use of corticosteroids in short-term schemes (duration shorter than 3 days) for indications such as prophylaxis of reactions to intravenous contrast for imaging studies or chemotherapy-related adverse events (AEs) are not considered part of this exclusion. Prior use of corticosteroids for brain metastasis ending at least 14 days prior to enrollment is not considered part of this exclusion criteria\n* Pregnant and breastfeeding women are excluded from this study because of the potential for teratogenic or abortifacient effects with all of the agents involved in this trial. Females of childbearing potential who are pregnant, breast feeding, intend to become pregnant, or are not using adequate contraceptive methods or males who are not using adequate contraceptive methods. Women of childbearing potential must agree to use two methods of adequate contraception at study entry be used for the duration of study participation and for at least 7 months for women and 6 months for men after the final dose of any study-related medications\n* Clinically significant cardiomyopathy, coronary disease, myocardial infarction, chronic heart failure (CHF) (New York Heart Association class III or IV or hospitalization for CHF), ejection fraction \\\u003C 50% or cerebrovascular accident within 6 months prior to enrollment\n* Patients with a history of myocarditis are excluded due to the potential of myocarditis with anti-PD-L1 antibodies or other immunotherapies\n* Patients who have received any live vaccines within 30 days prior to enrollment (inactivated vaccines including COVID vaccines are allowed)\n* Any other condition, which would, in the opinion of the principal investigator the subject is a poor candidate for the clinical trial or would jeopardize the subject or the integrity of the data obtained\n* Inadequate pulmonary function defined as evidence of dyspnea at rest, exercise intolerance, and\u002For chronic oxygen requirement. In addition, room air pulse oximetry \\\u003C 90% and\u002For abnormal pulmonary function tests within 28 days of C1D1 if these assessments are clinically indicated.",{"count":453,"type":20},42,[66,23],"This phase Ib\u002FII trial tests the safety, best dose and how well gemcitabine and ex vivo expanded allogenic universal donor TGFBi NK cells with or without naxitamab work for the treatment of patients with GD2 expressing, HER2 negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. TGFBi NK cells are manufactured cells that are a part of your natural immunity. NK cells can recognize missing or incorrect proteins on tumor cells and then eliminate these tumor cells and TGFBi NK cells are created to be able to better kill the tumor cells. Naxitamab is a monoclonal antibody that targets GD2, which is a protein or sugar present on tumor cells but not very commonly found on normal cells. This antibody helps draw the attention of the immune system to the tumor cells that have GD2 to help attack the tumor cells. Giving gemcitabine and TGFBi NK cells with or without naxitamab may kill more tumor cells in patients with metastatic GD2 expressing, HER2 negative breast cancer.",[28,457],"HER2-Negative Breast Carcinoma","2026-07-21",{"date":460,"type":45},"2026-07-23",{"date":462,"type":45},"2024-04-02",{"date":464,"type":20},"2027-10-31",{"name":466,"class":173},"Margaret Gatti-Mays",{"id":468,"slug":469,"hasResults":12,"nctId":470,"briefTitle":471,"officialTitle":472,"acronym":4,"eligibilityCriteria":473,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":474,"targetDuration":4,"studyType":21,"phases":476,"briefSummary":477,"conditions":478,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":496,"lastUpdatePostDateStruct":497,"startDateStruct":499,"completionDateStruct":501,"leadSponsor":503,"locationsCount":174},"100446805","phase-1-personalized-neo-antigen-peptide-vaccine-for-the-treatment-of-stage-iiic-iv-melanoma-hormone-receptor-positive-her2-negative-metastatic-refractory-breast-cancer-or-stage-iii-iv-non-small-cell-lung-cancer-100446805","NCT05098210","Personalized Neo-Antigen Peptide Vaccine for the Treatment of Stage IIIC-IV Melanoma, Hormone Receptor Positive HER2 Negative Metastatic Refractory Breast Cancer or Stage III-IV Non-Small Cell Lung Cancer","PNV21-001: A Phase I Study of a Personalized Multi-Peptide Neo-Antigen Vaccine in Breast Cancer, Pre-Treated Nonsmall Cell Lung Cancer and PD1\u002FPD-L1 Inhibitor-Refractory Melanoma","Inclusion Criteria:\n\n* Female and\u002For male patients age \\>= 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2\n* Patients must have at least 1 lesion (or aggregate lesions) to obtain tumor tissue for resection of \\>= 1 cm or \\>= 4 core biopsies acceptable. Amenable to image (CT, ultrasound \\[U\u002FS\\], or magnetic resonance imaging \\[MRI\\]) guided biopsy for tissue collection necessary for neoantigen identification. Either primary or metastatic sites are options for tissue collection\n* Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria: Participants must have measurable disease, defined as at least one target lesion that can be measured in at least one dimension (longest diameter to be recorded) as \\>= 10 mm, unless lymph node in which case short axis must be \\>= 15 mm. Baseline imaging (for example diagnostic CT chest\u002Fabdomen\u002Fpelvis, PET CT scan and imaging of the affected extremity as appropriate), brain imaging (MRI or CT scan) must be obtained within 45 days of prior to start of first planned vaccine dose infusion. MRI can be substituted for CT in patients unable to have CT contrast\n* Serum creatine \\\u003C 1.5 mg\u002FdL or estimated glomerular filtration rate (eGFR) \\> 60 mL\u002Fmin\n* Total bilirubin (tBili) \\\u003C 1.5 x upper limit of normal (ULN) and an aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) \\\u003C 2.5 x ULN and \\\u003C 5 x ULN for subjects with documented liver metastasis. Patients with suspected Gilbert syndrome may be included if tBili \\> 3 but no other evidence of hepatic dysfunction\n* =\\\u003C grade 1 dyspnea and arterial oxygen saturation (SaO2) \\>= 92% on ambient air. If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, patients with forced expiratory volume in 1 second (FEVI) \\>= 70% of predicted and carbon monoxide diffusing capability (DLCO) (corrected) of \\>= 60% of predicted will be eligible\n* Patients with active interstitial lung disease (ILD)\u002Fpneumonitis or a history of ILD\u002Fpneumonitis requiring treatment with systemic steroids will be excluded\n* Patients 60 years of age or older are required to have left ventricular ejection fraction (LVEF) evaluation performed within 60 days prior to enrollment. LVEF may be established with echocardiogram or MUGA scan, and left ejection fraction must be \\>= 50%. Cardiac evaluation for other patients is at the discretion of the treating physician\n* Subjects with a history of myocarditis or congestive heart failure (as defined by New York Heart Association functional classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry will be excluded\n* Absolute neutrophil count (ANC) \\> 1000 cells\u002Fmm\\^3\n* Hemoglobin \\>= 9 mg\u002FdL\n* Platelet count \\>= 50,000\u002FuL\n* Toxicity from prior therapy must be recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.)5 grade 2 or less\n* Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures\n* Capable of understanding and providing a written informed consent\n* The effects of neoantigen vaccination on the developing human fetus are unknown. For this reason, patients who are having sex that can lead to pregnancy must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) for the duration of study participation. Should a woman become pregnant while participating in the study, she should inform her study doctor immediately and will not receive any more study treatment\n* MELANOMA SPECIFIC: Tissue confirmation of melanoma: Histologically confirmed metastatic (recurrent or de novo stage IV) or unresectable locally advanced (stage IIIC or IIID) cutaneous, acral, conjunctival or mucosal melanoma, as defined by the American Joint Committee on Cancer (AJCC) v8.0. Confirmation of diagnosis must be or have been performed by internal pathology review of archival, initial or subsequent biopsy or other pathologic material at Fred Hutchinson Cancer Center (FHCC)\u002FUniversity of Washington Medical Center (UWMC)\n* MELANOMA SPECIFIC: Patients must have received stage specific standard of care therapy per National Comprehensive Cancer Network (NCCN) guidelines and have persistent\u002Frecurrent disease after at least one line of therapy prior to enrollment on the study\n* MELANOMA SPECIFIC: Known BRAF mutational status\n* MELANOMA SPECIFIC: History of detectable disease during\u002Fafter treatment with a PD-1 or PD-L1 inhibitor, as defined by the Society of Immunotherapy of Cancer's definition of primary or secondary resistance (Kluger and others \\[et al.\\], 2020):\n\n  * Drug exposure \\>= 6 weeks and best response progressive disease (PD) or stable disease (SD) \\\u003C 6 months or\n  * Drug exposure \\>= 6 months and best response complete response (CR), partial response (PR), or SD \\> 6 months\n* MELANOMA SPECIFIC: A confirmatory scan performed at least 4 weeks after disease persistence\u002Fprogression is required but this requirement can be waived if the judgement of the treating clinician is that the patient would be at risk of rapid or symptomatic progression in that interval. This confirmatory scan can occur during production of the vaccine after enrollment\n* BREAST CANCER SPECIFIC: Tissue confirmation of stage IV (recurrent or de novo metastatic) hormone receptor (HR) positive, HER2 negative breast cancer:\n\n  * Hormone receptor (HR) positive breast cancer as defined by either one, or both of the following criteria:\n\n    * Estrogen receptor (ER) positive disease defined as follows documented by a local laboratory: 1-100% positive stained cells based on de novo tumor biopsy\n    * Progesterone receptor (PR) positive disease defined as follows documented by a local laboratory: 1-100% positive stained cells based on de novo tumor biopsy\n  * Human epidermal growth factor receptor 2 (HER2) negative breast cancer (per American Society of Clinical Oncology \\[ASCO\\]\u002FCollege of American Pathologists \\[CAP\\] guideline update, 2018) as documented by a local laboratory with HER2-negativity defined as:\n\n    * Immunohistochemistry score 0\u002F1+ or 2+ and \u002F or\n    * Negative by in situ hybridization (fluorescence in situ hybridization \\[FISH\\]\u002Fchromogenic in situ hybridization \\[CISH\\]\u002Fsilver-enhanced in situ hybridization \\[SISH\\]) per ASCO\u002FCAP guideline update, 2018\n  * Confirmation of diagnosis must be or have been performed by internal pathology review of archival, initial or subsequent biopsy or other pathologic material at FHCC\u002FUWMC\n* BREAST CANCER SPECIFIC: Patients must have received at least one line of systemic therapy in the metastatic setting prior to enrollment on the study and have progressive\u002Fpersistent disease after\n* NON-SMALL CELL LUNG CANCER SPECIFIC: Tissue confirmation of stage III unresectable or stage IV (recurrent or de novo metastatic) non-small cell lung cancer (NSCLC):\n\n  * Genetic testing must have been performed for targetable driver mutations, including EGFR, ROS1, Alk, KRAS, BRAF\n  * Confirmation of diagnosis must be or have been performed by internal pathology review of archival, initial or subsequent biopsy or other pathologic material at FHCC\u002FUWMC\n* NON-SMALL CELL LUNG CANCER SPECIFIC: Patients must have received at least one line of systemic therapy in the metastatic or stage II or III setting including a PD-1 or PD-L1 inhibitor prior to enrollment on the study and have progressive or recurrent disease after\n* NON-SMALL CELL LUNG CANCER SPECIFIC: For patients who have received neoadjuvant, adjuvant, and\u002For consolidation anti-PD-1 or anti-PD-L1 for stage II or III disease, they must have experienced disease progression in less than or equal to 365 days from initiation (cycle 1 day 1) of anti-PD-1 or anti-PD-L1 therapy for this to count as the systemic therapy for advanced disease. Patients experiencing progression more than 365 days from initiation (cycle 1 day 1) of anti-PD-1 or anti-PD-L1 therapy will not be considered as having received one line of systemic therapy. These patients must have received an anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent disease\n\nExclusion Criteria:\n\n* Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 5 months after the last dose of investigational product\n* Any history of an immune-related grade 4 adverse event attributed to prior cancer immunotherapy CIT (other than endocrinopathy managed with replacement therapy or asymptomatic elevation of serum amylase or lipase)\n* Any history of an immune-related grade 3 adverse event attributed to prior CIT that required permanent discontinuation of PD-1 inhibitor therapy\n* Immune-related adverse events related to prior CIT (other than endocrinopathy managed with replacement therapy or stable vitiligo) that have not resolved to baseline. Patients treated with corticosteroids for immune-related adverse events must demonstrate absence of related symptoms or signs for \\>= 4 weeks following discontinuation of corticosteroids\n* Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated \\> 4 weeks prior to enrollment. Patients should be recovered from the effects of radiation\n* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters (e.g., PleurX®) are allowed\n* Patients with known symptomatic brain metastases. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable for \\>= 1 months (confirmed by magnetic resonance imaging \\[MRI\\])\n* Patients with rapidly progressing disease, symptomatic visceral disease, or patients who are expected to have rapidly progressive disease over the course of several months despite bridging therapy approved by the protocol\n* Known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T-negative severe combined immunodeficiency \\[SCID\\]) or combined T- and B-cell immunodeficiencies (e.g., T- and B-negative SCID, Wiskott-Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency)\n* Prior allogeneic bone marrow transplantation or prior solid organ transplantation\n* Known positive test for HIV infection\n* Patients with active infection causing fever (temperature \\> 38.1 degrees Celsius \\[C\\]) or subjects with unexplained fever (temperature \\> 38.1 degrees C) may not receive the investigational product unless the fever is =\\\u003C 38.1 for 5 days prior to start\n* Active uncontrolled infection: individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have, per standard practice, hepatitis well-controlled on medication (e.g., AST and ALT \\\u003C 5 x ULN) can be included\n* History of autoimmune disease that has not been controlled with treatment in the last 12 months, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions: Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., no psoriatic arthritis) may be eligible\n* Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone \\> 10 mg\u002Fday or equivalent, cyclophosphamide, azathioprine, methotrexate, thalidomide, and TNF-alpha antagonists) within 2 weeks prior screening. The use of topical, eye drops, local injections, or inhaled corticosteroids (e.g. fluticasone for chronic obstructive pulmonary disease) is allowed. The use of oral mineralocorticoids (e.g. fludrocortisone for patients with orthostatic hypotension) is allowed. Physiologic doses of corticosteroids for adrenal insufficiency are allowed. Low dose corticosteroids for a short duration \\[5 mg once daily (QD) prednisone for 2 weeks\\] as symptomatic treatment and upon with discussion with the investigator is allowed. Note: Patients with adrenal insufficiency may take 10 mg of prednisone or equivalent daily\n* Subjects should have an international normalized ratio (INR) or activated partial thromboplastin time (aPTT) =\\\u003C 1.5 X ULN unless the subject is receiving anticoagulant therapy. Subjects on anticoagulant therapy should have a prothrombin time (PT) or partial thromboplastin time (PTT) within therapeutic range of intended use and no history of severe hemorrhage. Antiplatelet agents (eg, aspirin, clopidogrel, etc.) are not considered anticoagulants for the purposes of this study (i.e., they are allowed)\n* Other medical, social, or psychiatric factor that interferes with medical appropriateness and\u002For ability to comply with study, as determined by the principal investigator (PI)\n* Participants of childbearing potential must have a negative serum pregnancy test within 14 days prior to enrollment. Childbearing potential is defined as women who have not been surgically sterilized and who are not post-menopausal (free of menses for at least 1 year)\n* Female patients who are lactating or intend to breastfeed during the duration of the study\n* Patients who have received a live vaccine within 30 days prior to enrollment\n* Patients with any underlying medical condition for which, in the investigator's opinion, participation would not be in the best interest of the participant (e.g.- compromises the health of the subject) or that could prevent, limit or confound protocol assessments\n* MELANOMA SPECIFIC: Uveal or choroidal melanoma. This entity is excluded due to the absence of abundant mutations\n* BREAST SPECIFIC: Patients with symptomatic disease including patients with symptomatic lung metastases, bone marrow replacement with associated cytopenia, or significant liver metastases with associated liver dysfunction\n* NON-SMALL CELL LUNG CANCER SPECIFIC: Activating mutations in EGFR or genetic alterations in ROS1 or Alk, as these mutations are associated with lower mutation burden and non-response to immune therapies",{"count":475,"type":20},28,[66],"This phase I trial studies the safety of personalized neo-antigen peptide vaccine in treating patients with stage IIIC-IV melanoma, hormone receptor positive HER2 negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or does not respond to treatment (refractory) or stage III-IV non-small cell lung cancer. Personalized neo-antigen peptide vaccine is a product that combines multiple patient specific neo-antigens. Given personalized neo-antigen peptide vaccine together with Th1 polarizing adjuvant poly ICLC may induce a polyclonal, poly-epitope, cytolytic T cell immunity against the patient's tumor.",[28,76,479,480,481,482,483,31,484,108,32,485,486,487,488,489,490,491,492,118,135,493,494,152,495],"Locally Advanced Cutaneous Melanoma","Locally Advanced Mucosal Melanoma","Metastatic Acral Melanoma","Metastatic Conjunctival Melanoma","Metastatic Cutaneous Melanoma","Metastatic Hormone Receptor-Positive Breast Carcinoma","Metastatic Mucosal Melanoma","Pathologic Stage IIIC Cutaneous Melanoma AJCC v8","Pathologic Stage IIID Cutaneous Melanoma AJCC v8","Recurrent Cutaneous Melanoma","Recurrent HER2-Negative Breast Carcinoma","Recurrent Hormone Receptor-Positive Breast Carcinoma","Recurrent Lung Non-Small Cell Carcinoma","Recurrent Mucosal Melanoma","Unresectable Acral Melanoma","Unresectable Cutaneous Melanoma","Unresectable Mucosal Melanoma","2026-07-20",{"date":498,"type":45},"2026-07-22",{"date":500,"type":45},"2022-06-09",{"date":502,"type":20},"2028-11-01",{"name":504,"class":173},"Fred Hutchinson Cancer Center",{"id":506,"slug":507,"hasResults":12,"nctId":508,"briefTitle":509,"officialTitle":510,"acronym":4,"eligibilityCriteria":511,"healthyVolunteers":12,"sex":313,"minAge":182,"maxAge":4,"enrollmentInfo":512,"targetDuration":4,"studyType":21,"phases":514,"briefSummary":515,"conditions":516,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":518,"lastUpdatePostDateStruct":519,"startDateStruct":520,"completionDateStruct":522,"leadSponsor":524,"locationsCount":242},"100389274","phase-2-dendritic-cell-vaccines-against-her2her3-and-pembrolizumab-for-the-treatment-of-brain-metastasis-from-triple-negative-breast-cancer-or-her2-breast-cancer-100389274","NCT04348747","Dendritic Cell Vaccines Against Her2\u002FHer3 and Pembrolizumab for the Treatment of Brain Metastasis From Triple Negative Breast Cancer or HER2+ Breast Cancer","A Phase IIa Study of Dendritic Cell Vaccines Against Her2\u002FHer3 and Pembrolizumab in Patients With Asymptomatic Brain Metastasis From Triple Negative Breast Cancer (TNBC) or HER2+ Breast Cancer (HER2+BC) or Hormone Receptor Positive (HR+) Breast Cancer.","Inclusion Criteria:\n\n* female participant is eligible to participate if she is not pregnant,not breastfeeding, and at least one of the following conditions applies:\n\n  * Not a woman of childbearing potential (WOCBP)\n  * A WOCBP who agrees to follow contraceptive guidance\n* WOCBP must agree to use acceptable birth control methods for the duration of the study and until persistence of the study drug is no longer detected in the peripheral blood:this may be a period of several years. Methods for acceptable birth control include: condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception; it is recommended that a combination of two methods be used. NOTE: If the risk of conception exists, patients must agree to use highly effective contraception throughout the study and for at least two years following the last study treatment administration\n* Negative serum and highly sensitive urine pregnancy test(s):\n* At initial screening prior to eligibility confirmation\n* within 72 hours prior to leukapheresis if \\>72 hours have passed between screening test and the Leukapheresis visit\n* Pregnancy testing will be performed for WOCBP and interpreted prior to every cycle of pembrolizumab (Initial Treatment Phase);\n* at the End of Treatment (EOT) Assessment; and\n* whenever pregnancy is otherwise suspected. Note: In the event that 72 hours have elapsed between the screening pregnancy test and leukapheresis, another pregnancy test must be performed and must be negative in order for subject to undergo leukapheresis\n* Histologically or cytologically confirmed diagnosis of triple negative breast cancer (TNBC) (estrogen receptor \\[ER\\] =\\\u003C 1%, progesterone receptor \\[PR\\] =\\\u003C 1% HER2 negative) or HR+ breast cancer\n\n  * HER2 testing should be performed on the invasive component using a validated immunohistochemistry (IHC) or in situ hybridization (ISH) assay\n  * IHC staining is defined as:\n\n    * IHC 3+ if there is complete and intense circumferential membrane staining within \\> 10 percent of tumor cells. All IHC 3+ tumors are considered HER2 positive\n    * IHC 2+ if there is incomplete and\u002For weak\u002Fmoderate, circumferential membrane staining within \\> 10 percent of tumor cells. All IHC 2+ tumors are reported as HER2 equivocal\n    * IHC 1+ if there is faint or barely perceptible, incomplete membrane staining within \\> 10 percent of tumor cells. All IHC 1+ tumors are reported as HER2 negative\n    * IHC 0 if (1) no staining is observed, or (2) there is faint or barely perceptible, incomplete membrane staining within \\\u003C 10 percent of tumor cells. All IHC 0 tumors are reported as HER2 negative\n    * Equivocal HER2 testing should trigger reflex HER2 testing using ISH on the same specimen or a new test (using a different specimen with either IHC or ISH)\n  * Results from ISH are defined as the ratio of gene amplification of HER2 and the chromosome 17 enumeration probe (CEP17). Results are reported as:\n\n    * ISH positive if the HER2\u002FCEP17 ratio is \\>= 2.0, and the HER2 copy number signals\u002Fcell is \\>= 4\n    * Definitive diagnosis will be rendered pending further workup in the following instances:\n\n      * If the HER2\u002FCEP17 ratio is \\>= 2.0 and an average HER2 copy number is \\\u003C 4.0 signals\u002Fcell - negative if confirmed on retesting\n      * If the HER2\u002FCEP17 ratio is \\\u003C 2.0 and the average HER2 copy number is \\>= 6.0 signals\u002Fcell positive - if confirmed on retesting\n      * If the HER2\u002FCEP17 ratio is \\\u003C 2.0 and an average HER2 copy number is between \\>= 4.0 and \\\u003C 6.0 signals\u002Fcell negative - if confirmed on retesting\n    * ISH negative if the HER2\u002FCEP17 ratio is \\\u003C 2.0 and average HER2 copy number is \\\u003C 4.0 signals\u002Fcell\n* Measurable brain disease as per RANO-BM criteria modified to include the cut off point of 0.5 cm or higher. Have at least one untreated (includes irradiation) brain metastasis approved by a research team that meets the following size requirements:\n\n  * \\>= 0.5 cm AND twice the magnetic resonance imaging (MRI) slice thickness; and\n  * \\\u003C 3.0 cm, that is asymptomatic and does not require local therapy at the time of enrollment (i.e. target lesion\\[s\\])\n  * Of note, lesions \\>= 0.5 cm and \\\u003C 3 cm may be determined ineligible by the research team because of location or symptoms. An untreated brain metastasis is defined as a lesion not present at the time of whole brain radiation therapy or not included in a stereotactic radiotherapy field (or within 0.5 cm of a treated lesion), or any lesion that is new or unequivocally progressing since prior radiation therapy or prior surgery.\n* Any brain metastasis \\>= 3.0 cm or causing symptoms must have previously been treated with local therapy (i.e. radiation or surgical resection, as clinically appropriate) prior to study enrollment. Any lesion present at the time of whole brain radiation therapy (WBRT) or included in the stereotactic radiotherapy field (or within 5 mm of the treated lesion) will NOT be considered evaluable unless it is new or documented to have progressed since treatment\n* Stereotactic radiosurgery (SRS) and\u002For prior radiotherapy is permitted \\>=2 weeks prior to initial Dendritic Cell (DC) vaccine dose (leaving one or more lesions which are not radiated and will be used as target lesions) but a follow up brain MRI should be obtained prior to dendritic cell (DC) vaccine to determine stability of the lesions. An interval of at least 4 weeks after the end of whole brain radiation or for any surgical resection of brain lesions is permitted ; an interval of at least 4 weeks or 5 half-lives (whichever is sorter) after the last cytotoxic, targeted, immunotherapeutic or investigational agent is permitted (prior to the start of DC vaccine)\n\n  * Previous whole brain radiation is allowed if patient has been diagnosed with recurrent, progressive brain metastasis. Previously irradiated lesions would be considered non-target lesions\n  * Previously resected lesions or those treated with SRS would be considered nontarget lesions. There is no limitation on prior local therapies to other lesions.\n* If subject received major surgery, they must have recovered adequately from the toxicity and\u002For complications from the intervention prior to starting therapy\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n* Toxicity that has not recovered to \\\u003C=Grade 1 is allowed if it meets the inclusion requirments for lab parameters (Participants with \\\u003C= Grade 2 neuropathy may be eligible)\n* Patients must have adequate organ and marrow function as defined below (specimens must be collected within 10 days prior to the start of study treatment):\n* Hemoglobin \\>= 9 g\u002FdL or \\>= 5.6 mmol\u002FL\n* Leukocytes: \\>= 3 x 10\\^9\u002FL\n* Absolute neutrophil count: \\>= 1.5 x 10\\^9\u002FL\n* Platelets: \\>= 100 x 10\\^9\u002FL\n* Total bilirubin: =\\\u003C 1.5 x upper limit of normal (ULN) OR direct bilirubin =\\\u003C ULN for participants with total bilirubin levels \\> 1.5 x ULN\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]): =\\\u003C 2.5 x institutional upper limit of normal (=\\\u003C 5 x ULN for participants with liver metastases)\n* Creatinine OR Measured or calculated creatinine clearance (Glomerular Filtration Rate (GFR) can also be used in place of creatinine or CrCl): ≤1.5 × ULN OR ≥30 mL\u002Fmin for participant with creatinine levels \\>1.5 × institutional ULN\n* International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (APTT) =\\\u003C 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants\n* No evidence of leptomeningeal disease\n* If patient is on steroids, they must be on a steroid dose less than or = to an equivalent prednisone dose of 10 mg daily\n* Life expectancy of \\> 3 months\n* Prior checkpoint inhibitors permitted 3 weeks prior to enrollment\n* If the disease has progressed on current treatment in the CNS, prior to consent, patients may continue Her 2 directed antibody treatment (trastuzumab and pertuzumab); aromatase inhibitor or tamoxifen while on the study; patients with triple negative breast cancer may continue capecitabine, eribulin or paclitaxel while on study per PI discretion\n* Patients with systemic disease will be managed as detailed in Section 10.1 - Patients who develop systemic disease progression on the protocol will be managed as detailed in Section 10.4.2\n\nExclusion Criteria:\n\n* Any condition which might confound the results of the study, interfere with the subject's participation for full participation (for the full duration of the study) or in the Investigator's opinion deems the participant an unsuitable candidate for the study\n* Symptomatic brain metastases. Any neurologic symptoms present must have resolved with local therapy by the time of administration of study drugs\n* May not be receiving any other investigational agents and may not have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of DC vaccine treatment\n* Has had prior chemotherapy or targeted small molecule therapy (except treatment mentioned in inclusion criteria 17) within 4 weeks or 5 half-lives (whichever is sooner) prior to start of treatment (first DC vaccine) or who has not recovered (i.e., =\\\u003C grade 1 or at baseline) from adverse events due to a previously administered agent. Previous radiation to extracranial sites may be completed at any time prior to initiation of study drugs (first DC vaccine) with a 2-week washout is required.\n* Rapidly progressing systemic disease which might interfere with completion of all the vaccine doses\n* Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed\n* History of allogenic tissue\u002Fsolid organ transplantation\n* Has an active infection requiring systemic therapy which in the investigator's opinion will increase risk to the patient\n* Has known active hepatitis B or hepatitis C infection (Testing is not mandatory)\n* Has known immunosuppressive disease (e.g. human immunodeficiency virus \\[HIV\\], acquired immunodeficiency syndrome \\[AIDS\\] or other immune depressing disease). Testing is not mandatory\n* Has received a blood transfusion in the two weeks prior to leukapheresis\n* Pregnant or actively nursing (females who agree to stop nursing would be eligible) participants\n* Unwilling or unable to follow protocol requirements\n* Brain lesion size with significant midline shift or obstructive hydrocephalus\n* The use of corticosteroids to control cerebral edema or treat neurologic symptoms will not be allowed unless at a low dose, not to exceed 10 mg of prednisone (or equivalent) per day\n* History of stroke or transient ischemic attack within 6 months prior to study enrollment\n* History of (non-infectious) pneumonitis \u002Finterstitial lung disease that required steroids, or has current pneumonitis\u002F interstitial lung disease\n* Presence of leptomeningeal disease\n* Any contraindication to MRI (i.e., patients with pacemakers or other metal implanted medical devices). An MRI safety questionnaire is required prior to MR imaging\n* Has received prior radiotherapy within 2 weeks of start of study treatment with dendritic cell (DC) vaccine and\u002For has received SRS \\\u003C2. weeks prior to the administration of the first DC vaccine dose. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\\\u003C 2 weeks of radiotherapy) to non-CNS disease\n* Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Seasonal influenza vaccines for injection are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed. Administration of killed vaccines is allowed.\n* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug (DC vaccine)\n* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded\n* A WOCBP who has a positive urine or blood pregnancy test at screening and within 72 hrs prior to leukapheresis\n\n  \\*Note: in the event that 72 hrs have elapsed between the initial screening pregnancy test and leukapheresis, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to undergo leukapheresis\n* Known active carcinomatous meningitis\n* Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.",{"count":513,"type":20},23,[23],"This phase IIa trial studies how well dendritic cell vaccines against Her2\u002FHer3 and pembrolizumab work for the treatment of triple negative breast cancer or HER2+ breast cancer or HER+ Breast cancer that has spread to the brain (brain metastasis). Dendritic cell vaccines work by boosting the immune system (a system in the body that protect against infection) to recognize and destroy the cancer cells. . Pembrolizumab is an \"immune checkpoint inhibitor\" which is designed to either \"unleash\" or \"enhance\" the cancer immune responses that already exist by either blocking inhibitory molecules\" or by activating stimulatory molecules. Giving dendritic cell vaccines and pembrolizumab may shrink the cancer.",[28,214,113,517],"Prognostic Stage IV Breast Cancer AJCC v8","2026-07-17",{"date":458,"type":45},{"date":521,"type":45},"2022-12-19",{"date":523,"type":20},"2028-05-15",{"name":525,"class":173},"Roswell Park Cancer Institute",{"id":527,"slug":528,"hasResults":12,"nctId":529,"briefTitle":530,"officialTitle":530,"acronym":4,"eligibilityCriteria":531,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":532,"targetDuration":4,"studyType":21,"phases":534,"briefSummary":535,"conditions":536,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":586,"lastUpdatePostDateStruct":587,"startDateStruct":589,"completionDateStruct":591,"leadSponsor":593,"locationsCount":174},"100446356","phase-1-phase-i-study-of-tumor-treating-fields-ttf-in-combination-with-cabozantinib-or-with-pembrolizumab-and-nab-paclitaxel-in-patients-with-advanced-solid-tumors-involving-the-abdomen-or-thorax-100446356","NCT05092373","Phase I Study of Tumor Treating Fields (TTF) in Combination With Cabozantinib or With Pembrolizumab and Nab-Paclitaxel in Patients With Advanced Solid Tumors Involving the Abdomen or Thorax","Inclusion Criteria:\n\n* Participants must have pathologically confirmed advanced\u002Fmetastatic solid cancer (hepatocellular carcinoma, renal cell carcinoma, breast cancer, ovarian\u002Ffallopian, or endometrial\u002Fprimary peritoneal tumors) involving the abdomen or thorax, cannot tolerate standard therapy or have experienced tumor progression on standard therapy.\n* Age: ≥18 years.\n* Eastern Cooperative Oncology Group (ECOG) performance status 0-1.\n* Life expectancy \\>3 months.\n* Normal bone marrow function, defined as absolute neutrophil count ≥1,000\u002FµL; platelets ≥75,000\u002FµL; hemoglobin ≥8 g\u002FdL.\n* Adequate hepatic function as defined by a total bilirubin level ≤1.5 x the upper limit of normal (ULN), unless the patient has known Gilbert's syndrome, and alanine aminotransferase (ALT)\u002F serum glutamic pyruvic transaminase levels (SGPT) ≤2.5 x ULN (unless the patient has liver metastases: ALT)\u002F serum glutamic pyruvic transaminase levels (SGPT) ≤5 x ULN).\n* Participants with HCC must have a Child Pugh status A, no clinically significant ascites (requiring pharmacological or interventional treatment), and no history (or increased risk) of esophageal\u002Fgastric bleeding, impaired wound healing, perforation or fistula.\n* Serum creatinine clearance ≥50 mL\u002Fmin by the Cockcroft-Gault formula.\n* Measurable disease by RECIST or evaluable disease.\n* Contraception: Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Childbearing potential will be defined as women who have had menses within the past 12 months and who have not had a tubal ligation, hysterectomy, or bilateral oophorectomy. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately. Male participants must agree to use effective contraception or abstinence while on study.\n* Able to operate the TTF device independently or with the help of a caregiver.\n\nExclusion Criteria:\n\n* Participants must not receive prior anticancer therapy or radiation therapy within 2 weeks and must not undergo major surgery within 4 weeks prior to initiation of treatment on protocol. Participants who are already on cabozantinib and have progressive disease are allowed to transition to treatment with tumor treating fields and cabozantinib. Participants in both cohorts who already started treatments as standard of care (Cohort 1: Cabozantinib and Cohort 2: nab-paclitaxel and Pembrolizumab) are allowed to start on protocol within the first 2-3 weeks of treatment initiation. Palliative radiation therapy is allowed.\n* Participants must have recovered to Grade 0-1 toxicity from prior therapy.\n* Active brain metastasis or leptomeningeal disease. Patients with treated brain metastasis must have stable disease, evidenced by brain imaging for at least 4 weeks and the patient must have been off steroids for at least 2 weeks.\n* The patient has cardiac conditions as follows: uncontrolled: hypertension (blood pressure \\[BP\\] \\> 160\u002F100) despite optimal therapy, uncontrolled angina, ventricular arrhythmias, congestive heart failure (New York Heart Association Class II or above), prior or current cardiomyopathy, uncontrolled atrial fibrillation with heart rate \\> 100 beats per minute (bpm), unstable ischemic heart disease (myocardial infarction within 6 months prior to starting treatment or angina requiring use of nitrates more than once weekly).\n* The patient has concurrent severe and\u002For uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes, severe infection requiring active treatment, severe malnutrition, chronic severe liver or renal disease).\n* Concurrent malignancies are permitted if (A) they were previously treated, and all treatment of that malignancy was completed at least 2 years before enrollment and no evidence of disease exists, or (B) with agreement from the Principal Investigator (PI), participants who have a concurrent malignancy that is clinically stable and does not require tumor-directed treatment are eligible to participate if the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low, or (C) with agreement from the PI, other malignancies may be permitted if the risk of the prior malignancy interfering with either safety or efficacy end points is very low. Adequately treated basal or squamous cell carcinoma or carcinoma in situ is allowed.\n* The patient is pregnant or breastfeeding.\n* History of hypersensitivity or contraindication to TTF.\n* Implanted pacemaker, defibrillator or other electrical medical devices.\n* The participant has a previously-identified allergy or hypersensitivity to cabozantinib, nab-paclitaxel, or pembrolizumab, medical adhesives or hydrogel or the patient has received prior cabozantinib and discontinued therapy due to unacceptable toxicity.\n* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.\n* The patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.\n* CABOZANTINIB COHORT ONLY: The patient has experienced clinically-significant hematemesis or hemoptysis of \\> 0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment.\n* CABOZANTINIB COHORT ONLY: The patient has a cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel.\n* CABOZANTINIB COHORT ONLY: The patient has received drugs used to control loss of bone mass within 4 weeks prior to the first dose of study treatment.\n* CABOZANTINIB COHORT ONLY: The patient has prothrombin time\u002Finternational normalized ratio (PT\u002FINR) or partial thromboplastin time (PTT) test results that are above (1.3X) the laboratory upper limit of normal.\n* CABOZANTINIB COHORT ONLY: The subject has a corrected QT interval (QTcF) \\> 450 ms for men or \\> 470 ms for women.\n* CABOZANTINIB COHORT ONLY: The patient requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or FXa inhibitors, and antiplatelet agents. Low-dose aspirin (≤ 81 mg\u002Fday), low dose warfarin (≤ 1mg\u002Fday), and prophylactic low molecular weight heparin (LMWH) are permitted.\n* CABOZANTINIB COHORT ONLY: Patients with encasement of a major artery or bowel by tumor are excluded.\n* CABOZANTINIB COHORT ONLY: The patient is unable to swallow capsules.\n* CABOZANTINIB COHORT ONLY: History of hypersensitivity or contraindication to cabozantinib.\n* ATEZOLIZUMAB-CONTAINING COHORT: Participants who have received prior immunotherapy, including prior anti-PD-1 or anti-PD-L1 therapies may participate: (A) only if their prior anti-PD-1 or anti-PDL1 monotherapy or combination therapy were NOT the last treatment prior to participation on this study. (B) Participants who had prior immunotherapies and experienced Grade 1-2 immune-related adverse event (irAE) must have documentation that their irAEs are Grade 1 or 0 using current Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and participants must be off steroid therapy and\u002For other immunosuppressive therapy, as treatment for irAEs, for \\>= 14 days from Cycle 1, Day 1. (C) Participants who experienced Grade 3 irAEs consisting of laboratory abnormalities that were asymptomatic and have now resolved to Grade 1 or 0 and participants who have been off steroid and\u002For other immunosuppressive therapy, as treatment for irAEs, for \\>= 30 days from Cycle 1, Day 1. Participants with prior irAE pneumonitis (\\>= Grade 2) should not be given atezolizumab.\n* ATEZOLIZUMAB-CONTAINING COHORT: Human immunodeficiency virus (HIV) infection, active Hepatitis B or C infection, or active infections requiring oral or intravenous antibiotics.\n* ATEZOLIZUMAB-CONTAINING COHORT: Has received a live vaccine within 30 days prior to first dose.\n* ATEZOLIZUMAB-CONTAINING COHORT: Active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.\n* ATEZOLIZUMAB-CONTAINING COHORT: Serious autoimmune disease at the discretion of the treating attending: Patients with a history of active serious inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus or autoimmune vasculitis (e.g. Wegener's Granulomatosis) are excluded from this study.\n* ATEZOLIZUMAB-CONTAINING COHORT: History of\u002For current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician.",{"count":533,"type":20},43,[66],"This phase Ib trial tests the safety, side effects, and best dose of tumor treating fields therapy in combination with either cabozantinib or nab-paclitaxel and atezolizumab in treating patients with solid tumors involving the abdomen or thorax that have spread to other parts of the body (advanced). Tumor treating fields therapy on this study utilizes NovoTTF systems that are wearable devices that use electrical fields at different frequencies that may help stop the growth of tumor cells by interrupting cancer cells' ability to divide. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Chemotherapy drugs, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tumor treating fields therapy in combination with either cabozantinib, or with nab-paclitaxel and atezolizumab may help control advanced solid tumors involving the abdomen or thorax.",[537,538,539,540,541,542,543,544,545,546,27,69,70,71,28,547,548,189,103,549,107,550,551,552,553,554,111,555,556,557,558,517,559,117,560,561,119,562,563,121,564,565,123,566,567,568,569,570,125,571,572,127,573,574,575,129,130,131,576,134,577,578,136,579,580,138,581,582,140,583,142,584,585,144],"Advanced Breast Carcinoma","Advanced Endometrial Carcinoma","Advanced Fallopian Tube Carcinoma","Advanced Hepatocellular Carcinoma","Advanced Malignant Abdominal Neoplasm","Advanced Malignant Female Reproductive System Neoplasm","Advanced Malignant Thoracic Neoplasm","Advanced Ovarian Carcinoma","Advanced Primary Peritoneal Carcinoma","Advanced Renal Cell Carcinoma","Malignant Abdominal Neoplasm","Malignant Solid Neoplasm","Metastatic Fallopian Tube Carcinoma","Metastatic Malignant Abdominal Neoplasm","Metastatic Malignant Female Reproductive System Neoplasm","Metastatic Malignant Thoracic Neoplasm","Metastatic Ovarian Carcinoma","Metastatic Primary Peritoneal Carcinoma","Prognostic Stage III Breast Cancer AJCC v8","Prognostic Stage IIIA Breast Cancer AJCC v8","Prognostic Stage IIIB Breast Cancer AJCC v8","Prognostic Stage IIIC Breast Cancer AJCC v8","Stage III Fallopian Tube Cancer AJCC v8","Stage III Ovarian Cancer AJCC v8","Stage III Primary Peritoneal Cancer AJCC v8","Stage III Uterine Corpus Cancer AJCC v8","Stage IIIA Fallopian Tube Cancer AJCC v8","Stage IIIA Ovarian Cancer AJCC v8","Stage IIIA Primary Peritoneal Cancer AJCC v8","Stage IIIA1 Fallopian Tube Cancer AJCC v8","Stage IIIA1 Ovarian Cancer AJCC v8","Stage IIIA2 Fallopian Tube Cancer AJCC v8","Stage IIIA2 Ovarian Cancer AJCC v8","Stage IIIB Fallopian Tube Cancer AJCC v8","Stage IIIB Ovarian Cancer AJCC v8","Stage IIIB Primary Peritoneal Cancer AJCC v8","Stage IIIC Fallopian Tube Cancer AJCC v8","Stage IIIC Ovarian Cancer AJCC v8","Stage IIIC Primary Peritoneal Cancer AJCC v8","Stage IV Fallopian Tube Cancer AJCC v8","Stage IV Ovarian Cancer AJCC v8","Stage IV Primary Peritoneal Cancer AJCC v8","Stage IV Uterine Corpus Cancer AJCC v8","Stage IVA Fallopian Tube Cancer AJCC v8","Stage IVA Ovarian Cancer AJCC v8","Stage IVA Primary Peritoneal Cancer AJCC v8","Stage IVB Fallopian Tube Cancer AJCC v8","Stage IVB Ovarian Cancer AJCC v8","Stage IVB Primary Peritoneal Cancer AJCC v8","2026-07-15",{"date":588,"type":45},"2026-07-16",{"date":590,"type":45},"2022-04-29",{"date":592,"type":20},"2026-09-01",{"name":594,"class":173},"M.D. Anderson Cancer Center",{"id":596,"slug":597,"hasResults":12,"nctId":598,"briefTitle":599,"officialTitle":600,"acronym":4,"eligibilityCriteria":601,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":602,"targetDuration":4,"studyType":21,"phases":604,"briefSummary":605,"conditions":606,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":612,"lastUpdatePostDateStruct":613,"startDateStruct":615,"completionDateStruct":617,"leadSponsor":619,"locationsCount":620},"100603507","phase-1-testing-the-safety-of-the-combination-of-anti-cancer-drugs-cx-5461-pidnarulex-and-trastuzumab-deruxtecan-t-dxd-for-human-epidermal-growth-factor-receptor-2-her2-positive-solid-tumors-and-breast-cancer-100603507","NCT07137416","Testing the Safety of the Combination of Anti-Cancer Drugs CX-5461 (Pidnarulex) and Trastuzumab Deruxtecan (T-DXd) for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Solid Tumors and Breast Cancer","Phase 1b Study of Pidnarulex and Trastuzumab Deruxtecan in Patients With HER2 Expressing Solid Tumors","Inclusion Criteria:\n\n* DOSE ESCALATION PHASE ONLY: Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective\n* DOSE EXPANSION PHASE ONLY: Participants must have histologically or cytologically confirmed invasive breast cancer, with either locally advanced or metastatic disease\n* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of CX-5461 (pidnarulex) in combination with T-DXd in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)\n* Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL\n\n  * No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment\n* Platelets ≥ 100,000\u002FmcL\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n* Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (or ≤ 2 × institutional ULN in patients with documented Gilbert's syndrome)\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) ≤ 3 × institutional ULN (or ≤ 5 × ULN in patients with liver metastases)\n* International normalized ratio (INR)\u002Fprothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN\n* Glomerular filtration rate (GFR) ≥ 60 mL\u002Fmin\u002F1.73 m\\^2 (using the Cockcroft-Gault equation for participants with creatinine levels above institutional ULN)\n* Patients must have had at least one prior line of cytotoxic chemotherapy. Patients can have received an unlimited number of additional lines of chemotherapy, targeted therapy, biologic therapy, or hormonal therapy. Patients must not have progressed on a prior anthracycline in the metastatic setting. Receipt of anthracycline in the (neo)adjuvant setting is allowed, provided that disease recurrence occurred later than 6 months after the completion of treatment\n* Prior poly (ADP-ribose) polymerase (PARP) inhibition is allowed\n* No specific germline mutation is required\n* DOSE ESCALATION PHASE ONLY:\n\n  * HER2-positive (IHC 3+) solid cancers,\n  * HR+ HER2 positive\u002Flow\u002Fultralow breast cancer or triple negative breast cancer (TNBC) HER2-low breast cancer, with HER2 positive defined by the current American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guidelines,\n  * HER2-low, with HER2-low defined as IHC 2+\u002Fin situ hybridization (ISH)-, IHC 1+\u002FISH-, or IHC 1+\u002FISH untested\n* DOSE EXPANSION PHASE ONLY:\n\n  * Either the primary invasive tumor and\u002For the metastasis must be:\n\n    * HER2-low, with HER2-low defined as IHC 2+\u002FISH-, IHC 1+\u002FISH-, or IHC 1+\u002FISH untested. Any estrogen receptor (ER) and progesterone receptor (PR) expression is permitted but must be known, or\n    * HR+ HER2-ultralow defined as IHC 0 with membrane staining\n* Participants must have at least one lesion that is not within a previously radiated field that is measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Bone lesions are not considered measurable by definition. Biopsy of the lesion that will be used for disease evaluation (measurable disease) is not allowed in the dose expansion portion of this study\n* Peripheral neuropathy grade ≤ 1\n* Patients must have left ventricular ejection fraction (LVEF) ≥ 50% by either an echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within 28 days before randomization\u002Fenrollment\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* The effects of CX-5461 (pidnarulex) and T-DXd on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) 14 days prior to study entry and for the duration of study participation and for at least 7 months (women of childbearing potential \\[WOCBP\\] only) after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women should not breastfeed while taking CX-5461 (pidnarulex) and T-DXd and for 7 months after cessation of treatment. Men treated or enrolled on this protocol must also agree to use adequate contraception 14 days prior to the study, for the duration of study participation, and 6 months after completion of CX-5461 (pidnarulex) and T-DXd administration\n* Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \\[FSH\\] \\> 40 mIU\u002FmL and estradiol \\\u003C 40 pg\u002FmL \\[\\\u003C 147 pmol\u002FL\\] is confirmatory) or on ovarian suppression are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method\n* Male patients must not freeze or donate sperm starting at screening and throughout the study period, and at least 6 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in this study\n* Female patients must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives (LAR) may sign and give informed consent on behalf of study participants\n* Patients who have had chest radiation therapy within 4 weeks (2 weeks for palliative stereotactic radiation therapy). These patients will be excluded because T-DXd is known to increase the risk of developing pneumonitis\n\nExclusion Criteria:\n\n* Patients with a history of (non-infectious) interstitial lung disease (ILD) that required steroids, have current ILD, or where there is suspected ILD that cannot be ruled out by imaging at screening. These patients will be excluded because T-DXd is known to increase the risk of developing ILD and pneumonitis\n* Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \\[COPD\\], restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e., Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy at the time of screening. These patients will be excluded because T-DXd is known to increase the risk of developing ILD and pneumonitis\n* Patients who have had chemotherapy (including antibody drug therapy, retinoid therapy, hormonal therapy for cancer) within 3 weeks (2 weeks or five half-lives, whichever is longer for small-molecule targeted agents such as 5-fluorouracil-based agents, folinate agents), weekly paclitaxel; 6 weeks for nitrosoureas or mitomycin C. These patients will be excluded to allow for recovery of toxicities related to chemotherapy and minimize risk of drug interactions\n* Patients who have had cancer immunotherapy including monoclonal antibody therapy within 4 weeks\n* Patients who have had a major surgery within 4 weeks\n* Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade ≤ 1 or baseline. Patients with chronic grade 2 toxicities may be eligible (e.g., grade 2 chemotherapy-induced neuropathy). Patients should no longer be symptomatic nor require treatment with corticosteroids or anticonvulsants and must have recovered from the acute toxic effect of radiotherapy\n* Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity of CX-5461 (pidnarulex) will be determined based on their potential to interact with the CYP3A4 isozyme. Specifically, subjects taking strong CYP3A4 inhibitors or strong CYP3A4 inducers will be excluded from participation in the trial. A list of agents that interact with CYP450 isoenzymes is provided\n* Patients who are receiving any other investigational agents\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to CX-5461 (pidnarulex), T-DXd, or the inactive ingredients in the drug products, including patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies\n* Patients with a corrected QT interval (QTc) prolongation to \\> 470 ms (females) or \\> 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)\n* Patients with clinically significant corneal disease, cicatricial conjunctivitis or active ocular surface disease in the opinion of the investigator\n* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous\n* Pregnant women are excluded from this study because CX-5461 (pidnarulex) and T-DXd are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with CX-5461 (pidnarulex) and T-DXd, breastfeeding should be discontinued if the mother is treated with CX-5461 (pidnarulex) and T-DXd and avoided for 7 months after the last dose",{"count":603,"type":20},36,[66],"This phase I trial tests the safety, side effects, and best dose of pidnarulex in combination with trastuzumab deruxtecan in treating patients with breast cancer and other solid tumors that express varying levels of a protein called HER2 and that has spread from where it first started (primary site) to other places in the body (metastatic), that cannot be removed by surgery (unresectable), or that has spread to nearby tissue or lymph nodes (locally advanced). Pidnarulex is an enzyme inhibitor that causes cell death and prevents tumor cell growth. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Giving pidnarulex in combination with trastuzumab deruxtecan may be safe, tolerable and\u002For effective in treating patients with metastatic, unresectable, or locally advanced HER2-expressing breast cancer or other solid tumors.",[27,28,297,353,189,607,608,484,32,113,414,609,610,611,40,157],"Metastatic HER2-Low Breast Carcinoma","Metastatic HER2-Positive Breast Carcinoma","Unresectable HER2-Low Breast Carcinoma","Unresectable HER2-Positive Breast Carcinoma","Unresectable Hormone Receptor-Positive Breast Carcinoma","2026-07-10",{"date":614,"type":45},"2026-07-13",{"date":616,"type":20},"2026-10-05",{"date":618,"type":20},"2028-01-10",{"name":51,"class":52},2,{"id":622,"slug":623,"hasResults":12,"nctId":624,"briefTitle":625,"officialTitle":626,"acronym":4,"eligibilityCriteria":627,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":628,"targetDuration":4,"studyType":21,"phases":630,"briefSummary":632,"conditions":633,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":634,"lastUpdatePostDateStruct":635,"startDateStruct":637,"completionDateStruct":639,"leadSponsor":641,"locationsCount":174},"100468215","phase-4-an-investigational-scan-64cu-dota-trastuzumab-petmri-in-imaging-patients-with-her2-breast-cancer-with-brain-metastasis-100468215","NCT05376878","An Investigational Scan (64Cu-DOTA-Trastuzumab PET\u002FMRI) in Imaging Patients With HER2+ Breast Cancer With Brain Metastasis","Pilot Study to Evaluate 64Cu-DOTA-Trastuzumab Imaging in Patients With HER2+ Breast Cancer With Brain Metastatsis Treated With Fam-Trastuzumab Deruxtecan","Inclusion Criteria:\n\n* Documented informed consent of the participant and\u002For legally authorized representative\n* Women with documented metastatic HER2 positive breast cancer (American Society of Clinical Oncology \\[ASCO\\] College of American Pathologist \\[CAP\\] guidelines) who have brain metastases\n* Age \\> 18 years\n* Eastern Cooperative Oncology Group (ECOG) 0-2\n* Patients with leptomeningeal disease will be considered eligible\n* Planned therapy with fam-trastuzumab deruxtecan\n* Left ventricular ejection fraction (LVEF) \\> 50%\n* Absolute neutrophil count (ANC) \\> 1.5 x 10\\^9\u002FL\n* Platelets \\> 100 x 10\\^9\u002FL\n* Hemoglobin \\> 9 g\u002FdL\n* Total (T.) bilirubin \\\u003C 3 x upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \\\u003C 5 x ULN\n* Creatinine clearance \\> 30 ml\u002Fmin (by Cockcroft-Gault formula)\n* Activated partial thromboplastin time (aPTT) \\\u003C 1.5 x ULN\n* Prior therapy for central nervous system (CNS) disease is allowed, but at least 1 lesion \\> 1.5 cm is evident on MRI\n\nExclusion Criteria:\n\n* Need for immediate local intervention for brain metastases\n* Noninfectious interstitial lung disease or pneumonitis requiring glucocorticoids\n* Clinically significant corneal disease\n* Myocardial infarction \\\u003C 6 months before, congestive heart failure (CHF), unstable angina, or serious cardiac arrhythmia",{"count":629,"type":20},10,[631],"PHASE4","This clinical trial examines an investigational scan (64Cu-DOTA-trastuzumab positron emission tomography \\[PET\\]\u002Fmagnetic resonance imaging \\[MRI\\]) in imaging patients with HER2+ breast cancer that has spread to the brain (brain metastasis). Diagnostic procedures, such as 64Cu-DOTA-trastuzumab PET\u002FMRI, may help find HER2+ breast cancer that has spread to the brain and determine whether cancer in the brain takes up trastuzumab, which may predict for response to trastuzumab deruxtecan (the standard of care chemotherapy).",[28,189,214],"2026-06-29",{"date":636,"type":45},"2026-07-01",{"date":638,"type":45},"2022-12-21",{"date":640,"type":20},"2027-04-27",{"name":339,"class":173},{"id":643,"slug":644,"hasResults":12,"nctId":645,"briefTitle":646,"officialTitle":646,"acronym":4,"eligibilityCriteria":647,"healthyVolunteers":648,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":649,"targetDuration":4,"studyType":651,"phases":4,"briefSummary":652,"conditions":653,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":656,"lastUpdatePostDateStruct":657,"startDateStruct":659,"completionDateStruct":661,"leadSponsor":663,"locationsCount":174},"100644107","investigating-the-feasibility-and-acceptability-of-an-innovative-interdisciplinary-supportive-care-program-couples-coping-together-against-cancer-100644107","NCT07664579","Investigating the Feasibility and Acceptability of an Innovative Interdisciplinary Supportive Care Program: Couples Coping Together Against Cancer","Inclusion Criteria:\n\n* Have received a diagnosis of a primary brain tumor (glioblastoma), or other cancers (breast, lung, etc.)\n* Are new patients to City of Hope (COH) (all sites) or receive at least some of their care at City of Hope- Duarte Campus (care is defined as: procedures, consults, laboratories, imaging, surgery, and\u002For treatment)\n* The patient is in a committed relationship\u002Fpartnership with a partner and the partner is available and willing to participate\n* Are English or Spanish speaking\n* ≥ 18 years of age\n* Have access to a smartphone, computer\u002Flaptop or internet connection to complete all study procedures\n\nExclusion Criteria:\n\n* Significant cognitive impairment\n* Inpatient psychiatric treatment for severe mental illness or overt signs of severe psychopathology (e.g., psychosis)\n* Visual, hearing, voice, or motor impairment that prevents completion of study procedures as evidenced by clinical judgment\n* Committed partners will be excluded from the study if they:\n\n  * Refuse to complete informed consent\n  * Have cognitive impairment\n  * Have severe mental illness that would prevent informed consent and completion of study activities as evidenced by clinical judgment",true,{"count":650,"type":20},160,"OBSERVATIONAL","This study evaluates how useful and acceptable the components of the \"Couples Coping Together Against Cancer\", referred to as \"The Program\", are to the participants with cancer.",[28,654,655,548,189],"Glioblastoma","Lung Carcinoma","2026-06-18",{"date":658,"type":45},"2026-06-24",{"date":660,"type":45},"2024-07-05",{"date":662,"type":20},"2026-11-16",{"name":339,"class":173},{"id":665,"slug":666,"hasResults":12,"nctId":667,"briefTitle":668,"officialTitle":669,"acronym":4,"eligibilityCriteria":670,"healthyVolunteers":12,"sex":313,"minAge":182,"maxAge":4,"enrollmentInfo":671,"targetDuration":4,"studyType":21,"phases":673,"briefSummary":674,"conditions":675,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":656,"lastUpdatePostDateStruct":676,"startDateStruct":678,"completionDateStruct":680,"leadSponsor":682,"locationsCount":174},"100605092","phase-2-leuprolide-and-goserelin-for-ovarian-function-suppression-in-pre--or-peri-menopausal-women-with-breast-cancer-ofs-trial-100605092","NCT07158021","Leuprolide and Goserelin for Ovarian Function Suppression in Pre- or Peri-menopausal Women With Breast Cancer, OFS Trial","Phase 2 Interventional Trial of Ovarian Function Suppression for Breast Cancer (OFS)","Inclusion Criteria:\n\n* Female subject aged ≥ 18 years\n* Pre- or peri-menopausal patient, who had (1) menses either within the 12 months prior to or since breast cancer diagnosis or (2) estradiol concentration above the postmenopausal range per institutional laboratory guidance either within the 12 months prior to or since breast cancer diagnosis.\n* Planning to take GnRHa therapy in combination with oral endocrine therapy (tamoxifen, anastrozole, exemestane, or letrozole) for adjuvant treatment of stage 1-3 breast cancer or for treatment of metastatic breast cancer. Prior treatment with GnRHa therapy for treatment of non-oncologic conditions or during chemotherapy is permitted.\n* Not planning bilateral salpingo-oophorectomy during the 6-month study duration\n* Completion of chemotherapy, if given. Concurrent use of trastuzumab, pertuzumab, bisphosphonate therapy, poly adenosine diphosphate-ribose polymerase (PARP) inhibitor therapy, cyclin D kinase 4\u002F6 (CDK4\u002F6) inhibitor, and\u002For phosphoinositide 3-kinase (PI3K) inhibitor therapy is permitted\n* Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines\n\nExclusion Criteria:\n\n* Prior bilateral salpingo-oophorectomy\n* Known to be pregnant or breastfeeding (negative pregnancy test will be confirmed prior to study treatment initiation)\n* Concomitant use of systemic or transdermal estrogen products\n* Known allergy or hypersensitivity to goserelin or leuprolide, or any of the excipients in the medications\n* Unable to take oral medications\n* Any medical condition that would interfere with the absorption of endocrine therapy. Prior gastric bypass is permitted\n* Patients with a prior or concurrent malignancy whose natural history or treatment, in the opinion of the treating investigator, has the potential to interfere with the safety or efficacy assessment of the investigational regimen",{"count":672,"type":20},75,[23],"This phase II trial compares leuprolide to goserelin for reducing estrogen production by the ovaries in pre- or peri-menopausal women with breast cancer. Estrogen can cause the growth of breast cancer cells. Both leuprolide and goserelin lower the amount of estrogen made by the body. This may help stop the growth of tumor cells that need estrogen to grow. This study compares lower dose leuprolide, higher dose leuprolide, and goserelin for their ability to suppress the function of the ovaries to produce estrogen. Both doses of leuprolide may be as safe, tolerable and\u002For effective as goserelin in suppressing ovarian function in pre- or peri-menopausal women with breast cancer.",[320,321,27,28,189],{"date":677,"type":45},"2026-06-23",{"date":679,"type":45},"2026-01-22",{"date":681,"type":20},"2028-01-01",{"name":683,"class":173},"University of Michigan Rogel Cancer Center",{"id":685,"slug":686,"hasResults":12,"nctId":687,"briefTitle":688,"officialTitle":689,"acronym":4,"eligibilityCriteria":690,"healthyVolunteers":12,"sex":313,"minAge":182,"maxAge":4,"enrollmentInfo":691,"targetDuration":4,"studyType":651,"phases":4,"briefSummary":693,"conditions":694,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":696,"lastUpdatePostDateStruct":697,"startDateStruct":699,"completionDateStruct":701,"leadSponsor":703,"locationsCount":174},"100402252","immune-response-to-anti-her2-therapies-in-patients-with-her2-positive-stage-i-iv-breast-cancer-100402252","NCT04517838","Immune Response to Anti-HER2 Therapies in Patients With HER2-Positive Stage I-IV Breast Cancer","Immune Response to Anti-HER2 Therapies","Inclusion Criteria:\n\n* Age \\>= 18 years\n* Histological confirmed adenocarcinoma of the breast stage I-IV from the American Joint Committee on Cancer staging 8th edition\n* Any estrogen receptor (ER) or progesterone receptor (PR) but HER2 positive defined as per the most current American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guideline\n* Provide written informed consent\n* Willingness to provide blood samples for correlative research purposes\n* BLOOD AND TISSUE COHORT: Scheduled to start new anti-HER2 therapy\u002Ftherapies\n* TISSUE-ONLY COHORT: Received or previously completed anti-HER2 therapy\u002Ftherapies\n\nExclusion Criteria:\n\n* Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive\n* Receiving systemic steroid therapy or any other immunosuppressive therapy =\\\u003C 30 days prior to registration. NOTE: Inhaled steroids, low-dose corticosteroids (e.g. equivalent to or less than oral prednisone 10 mg daily), and steroid use for primary prevention of nausea per institutional guidelines are allowed.",{"count":692,"type":20},230,"This study gathers information from the blood cells and tumor tissue during treatment with anti-HER2 therapies, such as trastuzumab, pertuzumab, lapatinib, or neratinib, in patients with HER2 positive stage I-IV breast cancer who are scheduled to start anti-HER2 therapy. The information gained from this study may help researchers better understand the relation between cell response and anti-HER2 therapies.",[159,695,320,321,27,28],"HER2-Positive Breast Carcinoma","2026-06-12",{"date":698,"type":45},"2026-06-16",{"date":700,"type":45},"2020-07-31",{"date":702,"type":20},"2028-07-27",{"name":172,"class":173},{"id":705,"slug":706,"hasResults":12,"nctId":707,"briefTitle":708,"officialTitle":709,"acronym":4,"eligibilityCriteria":710,"healthyVolunteers":12,"sex":17,"minAge":182,"maxAge":4,"enrollmentInfo":711,"targetDuration":4,"studyType":21,"phases":713,"briefSummary":714,"conditions":715,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":731,"lastUpdatePostDateStruct":732,"startDateStruct":734,"completionDateStruct":736,"leadSponsor":738,"locationsCount":174},"100421724","phase-2-avapritinib-for-the-treatment-of-ckit-or-pdgfra-mutation-positive-locally-advanced-or-metastatic-malignant-solid-tumors-100421724","NCT04771520","Avapritinib for the Treatment of CKIT or PDGFRA Mutation-Positive Locally Advanced or Metastatic Malignant Solid Tumors","Phase 2 Study of Avapritinib in Patients With CKIT or PDGFRA Mutation-Positive Malignant Solid Tumors","Inclusion Criteria:\n\n1. The patient (or legally acceptable representative if applicable) provides written informed consent for the study.\n2. Male or female ≥18 years of age on the day of informed consent signing. Adolescent patients aged 12 years and older are allowed with signed assent and parental consent according to institutional guidelines and requirements.\n3. Cohorts 1 and 2: Patient has a locally advanced or metastatic solid tumor and has progressed on appropriate standard therapy, has not shown clinically meaningful benefit to appropriate standard therapy, has no available standard therapy, or has declined appropriate standard therapy.\n\n   • NOTE: Specific solid tumor types include but are not limited to melanoma, breast cancer, lung cancer, gastroesophageal cancer, colorectal cancer, sarcoma, solid tumors NOS, and primary CNS tumors. Patients with any other recurrent solid tumor type with the exception of gastrointestinal stromal tumor (GIST) will be eligible.\n4. Cohort 3: Patient has newly diagnosed IDH wild-type, MGMT-unmethylated glioblastoma. Patients must have received prior treatment with radiation and concurrent temozolomide per standard of care.27 Patients must have completed radiation and concurrent temozolomide 3-8 weeks prior to study treatment initiation.\n5. Measurable disease per the RECIST v1.1 or RANO criteria, as appropriate, for Cohorts 1 and 2. Patients in Cohort 3 can have measurable or non-measurable disease per the RANO criteria.\n\n6 Documented pathogenic CKIT activating mutation (Cohort 1) OR pathogenic PDGFRA activating mutation (Cohort 2) based on Clinical Laboratory Improvement Amendments-certified next-generation sequencing diagnostic test. Cohort 3 should have pathogenic CKIT or PDGFRA activating mutation\u002Famplification based on CLIA-certified NGS diagnostic test. CKIT and PDGFRA mutation pathogenicity will be verified by the MD Anderson Cancer Center's Precision Oncology Decision Support team. Acceptable CKIT\u002FPDGFRA mutations for study eligibility are listed in Appendix E.\n\n7\\. Has available archival tissue for CKIT\u002FPDGFRA mutation (amplification \\[Cohort 3 only\\]) retrospective testing.\n\n8\\. Adequate organ and marrow function as defined below within 7 days of study treatment initiation:\n\n* White blood cell count \\>2,500\u002FµL and \\\u003C15,000\u002FµL\n* Absolute neutrophil count ≥1.5 × 109\u002FL (without granulocyte colony-stimulating factor support within 2 weeks of laboratory test used to determine eligibility)\n* Platelet count ≥75 × 109\u002FL (without transfusion within 2 weeks of laboratory test used to determine eligibility)\n* Hemoglobin ≥9.0 g\u002FdL (without blood transfusion within 7 days of laboratory test used to determine eligibility)\n* Total bilirubin ≤1.5 × upper limit of normal (ULN); if hepatic metastases are present, ≤3.0 × ULN\n* Aspartate transaminase and alanine transaminase ≤2.5 × ULN; if hepatic metastases are present, ≤5.0 × ULN\n* Serum creatinine ≤2.0 × ULN or creatinine clearance ≥45 mL\u002Fmin. 9. Cardiac ejection fraction \\>45% per screening echocardiogram or multigated acquisition scan.\n\n  10\\. Eastern Cooperative Oncology Group performance status of 0-2.\n\n  11\\. Life expectancy ≥3 months.\n\n  12\\. Willing and able to comply with the protocol for the duration of the study including treatment and scheduled visits and examinations.\n\n  13\\. Willing to undergo biopsy as required by the study.\n\n  14\\. Females must be postmenopausal (defined as ≥45 years of age with at least 12 months of spontaneous amenorrhea) or premenopausal with documented surgical sterilization (tubal ligation, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), or evidence of non-childbearing status for women of childbearing potential (negative serum beta-human chorionic gonadotropin pregnancy test) within 3 days of study treatment initiation.\n\n  15\\. Females of childbearing potential must either abstain from heterosexual intercourse or use a highly effective method of contraception for the course of the study and for 6 weeks after the last dose of study treatment.\n\n  16\\. Males with female partners of reproductive potential must either abstain from sexual intercourse or they and their partners must use a highly effective method of contraception when engaging in sexual intercourse for the course of the study through 30 days after the last dose of study treatment.\n\nExclusion Criteria:\n\nPatients eligible for this study must not meet any of the following criteria:\n\n1. Patients who have GIST.\n2. Patients with tyrosine kinase inhibitor-resistant CKIT mutation V654A or T670I.\n3. Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or symptomatic or unstable brain metastases. Note: Patients with stable brain metastases (defined as asymptomatic or no requirement for high-dose or increasing dose of systemic corticosteroids) and without imminent need of radiation therapy) are eligible (including those with untreated brain metastases). If applicable, patients must have completed brain radiation therapy and recovered adequately from any associated toxicity and\u002For complications prior to eligibility assessment. For patients who have received prior radiation therapy, post-treatment magnetic resonance imaging scan should show no increase in brain lesion size\u002Fvolume.\n4. History of documented congestive heart failure (New York Heart Association functional classification III-IV) or serious cardiac arrhythmias requiring treatment.\n5. QT interval corrected using Fridericia's formula of \\>470 msec.\n6. Is currently participating or has participated in a study of an investigational agent or has used an investigational device within 2 weeks prior to study treatment initiation.\n7. Prior anticancer chemotherapy, hormone therapy, immunotherapy, targeted therapy, radiation therapy, or surgery within 2 weeks prior to study treatment initiation.\n\n   * NOTE: Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline (except alopecia). Patients with ≤ Grade 2 neuropathy are eligible.\n   * NOTE: If patient received major surgery, she\u002Fhe must have recovered adequately from the toxicity and\u002For complications from the intervention prior to study treatment initiation.\n   * NOTE: Patients in Cohort 3 must have completed radiation and concurrent temozolomide 3-8 weeks prior to study treatment initiation.\n8. Symptomatic non-healing wound, ulcer, gastrointestinal perforation, or bone fracture.\n9. History of psychotic or depressive disorder. Patients whose disorder is well controlled on a stable antipsychotic or antidepressant medication for at least 12 months prior to study entry will be eligible.\n10. Concomitant use of a known strong cytochrome P450 (CYP)3A4 inhibitor or strong CYP3A4 inducer. The required washout period prior to study treatment initiation is 2 weeks or 5 half-lives, whichever is shortest.\n11. Females who are pregnant or breastfeeding.\n12. Unable to swallow and retain oral medications.\n13. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the study treatment (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).\n14. Known additional malignancy that is progressing or requires active treatment. NOTE: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical cancer in situ that have undergone potentially curative therapy are not excluded.\n15. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the investigator.\n16. Prior treatment with an intracerebral agent or bevacizumab (Cohort 3 only).\n17. Prior treatment including radiation, chemotherapy, or immunotherapy for low-grade glioma (Cohort 3 only).",{"count":712,"type":20},50,[23],"This phase II trial studies the effect of avapritinib in treating malignant solid tumors that have a genetic change (mutation) in CKIT or PDGFRA and have spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Avapritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Avapritinib may help to control the growth of malignant solid tumors.",[28,78,81,83,29,91,716,717,32,109,718,719,720,721,722,723,724,725,558,517,726,128,727,135,728,139,729,143,730],"Locally Advanced Primary Malignant Central Nervous System Neoplasm","Locally Advanced Sarcoma","Metastatic Primary Malignant Central Nervous System Neoplasm","Metastatic Sarcoma","Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Stage IIIC Colorectal Cancer AJCC v8","Stage IV Colorectal Cancer AJCC v8","Stage IVA Colorectal Cancer AJCC v8","Stage IVB Colorectal Cancer AJCC v8","Stage IVC Colorectal Cancer AJCC v8","2026-06-09",{"date":733,"type":45},"2026-06-11",{"date":735,"type":45},"2021-01-20",{"date":737,"type":20},"2026-12-31",{"name":594,"class":173},{"id":740,"slug":741,"hasResults":12,"nctId":742,"briefTitle":743,"officialTitle":744,"acronym":4,"eligibilityCriteria":745,"healthyVolunteers":12,"sex":313,"minAge":182,"maxAge":4,"enrollmentInfo":746,"targetDuration":4,"studyType":21,"phases":748,"briefSummary":749,"conditions":750,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":752,"lastUpdatePostDateStruct":753,"startDateStruct":755,"completionDateStruct":757,"leadSponsor":759,"locationsCount":620},"100496202","phase-2-propranolol-and-pembrolizumab-for-tumor-re-sensitization-and-treatment-of-patients-with-checkpoint-inhibitor-refractory-metastatic-or-unresectable-triple-negative-breast-cancer-100496202","NCT05741164","Propranolol and Pembrolizumab for Tumor Re-sensitization and Treatment of Patients With Checkpoint Inhibitor Refractory Metastatic or Unresectable Triple Negative Breast Cancer","Impact of Beta-2 Adrenergic Blockade With Checkpoint Inhibition in Checkpoint Inhibitor Refractory Metastatic Triple Negative Breast Cancer","Inclusion Criteria:\n\n* Age \\>= 18 years of age\n* Have pathologically confirmed diagnosis of unresectable or metastatic triple negative breast cancer (TNBC) with no curative treatment options\n* No chemotherapy, radiotherapy, or major surgery within 4 weeks of protocol treatment\n* Checkpoint inhibitor refractory patients (i.e., no longer responding to chemotherapy and checkpoint inhibitor) who have disease progression on prior line of chemotherapy and pembrolizumab, and, who in the opinion of the physician, can continue checkpoint inhibitor\n* Patients must be agreeable to pre- and 6-week post treatment biopsy in part 1 of the study\n\n  * The pre-treatment biopsy for this study must be taken at least 4 weeks after all previous chemotherapy (pembrolizumab is allowed during this period)\n* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g. hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately\n* Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =\\\u003C 1\n* Platelets \\>= 100,000\u002FuL\n* Hemoglobin \\>= 9.0 g\u002FdL\n* Absolute neutrophil count (ANC) \\>= 1500\u002FuL\n* Total bilirubin =\\\u003C institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 2.5 X institutional ULN\n* Creatinine clearance \\>= 50 mL\u002Fmin per Cockcroft-Gault equation\n* HbA1C \\\u003C=8.5\n* Have measurable disease per RECIST 1.1 criteria present\n* Ability to swallow and retain oral medication\n* Participant must understand the investigational nature of this study and sign an Independent Ethics Committee\u002FInstitutional Review Board approved written informed consent form prior to receiving any study related procedure\n\nExclusion Criteria:\n\n* Patients currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 3 weeks after removal from immunosuppressive treatment\n* Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation\n* Patients with rapidly progressive disease\u002F symptomatic disease\n* Patients with primary resistance (i.e., did not respond to initial treatment with chemotherapy plus checkpoint inhibitor) with progressive disease at 12 weeks after starting chemotherapy and pembrolizumab\n* Patients who are pregnant or nursing. Women of childbearing potential (WOCBP) will have to undergo a urine pregnancy test as part of screening\n* Participants with symptomatic known brain metastases \\\u003C 4 weeks from radiation treatment should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events\n* History of malignancy other than breast cancer within 5 years prior to screening, with the exception of those with a negligible risk of metastases or death\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Unwilling or unable to follow protocol requirements\n* Contraindications to the use of beta-blockers, like: uncontrolled depression, unstable angina pectoris, uncontrolled heart failure (grade III or IV), hypotension (systolic blood pressure \\\u003C 100 mmHg), severe asthma or chronic obstructive pulmonary disease (COPD), uncontrolled type I or type II diabetes mellitus (hemoglobin A1C \\[HbA1C\\] \\> 8.5 or fasting plasma glucose \\> 160 mg\u002Fdl at screening), symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma, current use of beta-blockers or non-dihydropyridine calcium channel blockers\n* Any additional condition which in the investigator's opinion deems the participant an unsuitable candidate to receive the study drugs",{"count":747,"type":20},37,[23],"This phase II trial tests how well propranolol and pembrolizumab work to cause tumor re-sensitization and therefore treatment in patients with triple negative breast cancer that has not responded to previous checkpoint inhibitor therapy (refractory), cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). Propranolol is a drug that is classified as a beta-blocker. Beta-blockers affect the heart and circulation. Beta-blockers, like propranolol, may help to counteract effects of certain stress hormones produced by the body during cancer treatment and may increase the effectiveness of the pembrolizumab. Pembrolizumab is a drug that is classified as an immune checkpoint inhibitor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Propranolol may be able to re-sensitize the cells of the immune system to respond to the checkpoint inhibitor pembrolizumab in patients with checkpoint inhibitor refractory metastatic or unresectable triple negative breast cancer.",[27,28,113,751,157],"Refractory Triple-Negative Breast Carcinoma","2026-06-03",{"date":754,"type":45},"2026-06-04",{"date":756,"type":45},"2024-09-01",{"date":758,"type":20},"2029-06-30",{"name":760,"class":173},"Emory University"]