[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"invasive-breast-lobular-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:invasive-breast-lobular-carcinoma":128},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,142],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":130,"lastUpdatePostDateStruct":131,"startDateStruct":134,"completionDateStruct":136,"leadSponsor":138,"locationsCount":141},"100459958","phase-1-personalized-neoantigen-peptide-based-vaccine-in-combination-with-pembrolizumab-for-treatment-of-advanced-solid-tumors-100459958",false,"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.","ALL","16 Years",{"count":20,"type":21},138,"ESTIMATED","INTERVENTIONAL",[24,25],"PHASE1","PHASE2","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.",[28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128],"Anatomic Stage III Breast Cancer AJCC v8","Anatomic Stage IIIA Breast Cancer AJCC v8","Anatomic Stage IIIB Breast Cancer AJCC v8","Anatomic Stage IIIC Breast Cancer AJCC v8","Anatomic Stage IV 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 Malignant Solid Neoplasm","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 Malignant Solid Neoplasm","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 Malignant Solid Neoplasm","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","RECRUITING","2026-08-18",{"date":132,"type":133},"2026-08-20","ACTUAL",{"date":135,"type":133},"2022-03-31",{"date":137,"type":21},"2028-03-31",{"name":139,"class":140},"Mayo Clinic","OTHER",1,{"id":143,"slug":144,"hasResults":11,"nctId":145,"briefTitle":146,"officialTitle":146,"acronym":4,"eligibilityCriteria":147,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":149,"targetDuration":4,"studyType":22,"phases":151,"briefSummary":152,"conditions":153,"keywords":4,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":157,"lastUpdatePostDateStruct":158,"startDateStruct":160,"completionDateStruct":162,"leadSponsor":164,"locationsCount":166},"100509874","phase-2-neoadjuvant-neratinib-in-stage-i-iii-her2-mutated-lobular-breast-cancers-100509874","NCT05919108","Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast Cancers","Inclusion Criteria:\n\nEach patient will be entered into this study only if all of these criteria are met:\n\n* Subjects aged 18 years or older at signing of informed consent.\n* New diagnosis of clinical stage I-III HR+ histologically-proven (i.e. absent or decreased e-cadherin expression) invasive lobular carcinoma\n* Synchronous breast tumors are permitted as long as the synchronous tumor is ER+ and HER2-negative.\n* ER+ disease defined as ≥1% estrogen receptor (ER) positive consistent with current American Society of Clinical Oncology\u002FCollege of American Pathologists (ASCO\u002FCAP) or European Society of Medical Oncology (ESMO) guidelines)\n* At the time of screening, histologically confirmed cancers in patients with previously documented activating HER2 mutation (see Appendix A) confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent laboratory.\n* Archival tissue availability (if not available a fresh tumor biopsy will be required) and subject must agree to submission of sample for central testing\n* Minimum tumor size of ≥1.5 cm by US, mammogram, MRI imaging, or clinical breast exam\n* ECOG performance status 0 or 1\n* Patients must have adequate hematologic, hepatic, and renal function. All laboratory tests must be obtained within 1 month of study entry. This includes:\n\n  * Estimated glomerular filtration rate of ≥50 mL\u002Fmin\n  * Albumin ≥ 2.5 g\u002FdL\n  * ANC ≥1500\u002Fmm\\^3\n  * Platelet count ≥100,000\u002Fmm\\^3\n  * HgB ≥ 9 g\u002FdL\n  * Total serum bilirubin ≤ 1.5 x ULN (in patients with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN)\n  * AST and ALT ≤ 3 x ULN\n* Pre-, peri-, or post-menopausal, confirmed by history or laboratory testing as needed\n* Diagnostic biopsy tissue availability with sufficient tumor to permit NGS (if not available, a fresh biopsy will be required)\n* No prior treatment for current diagnosis of breast cancer\n* For patients who are not postmenopausal (women) or surgically sterile (absence of ovaries and\u002For uterus or vasectomy), agreement to remain abstinent or to use two adequate methods of contraception (e.g., condoms, diaphragm, vasectomy\u002Fvasectomized partner, tubal ligation), during the treatment period and for at least 30 days after the last dose of study treatment. Hormone based oral contraceptives are not allowed on study. Postmenopausal is defined as:\n\n  * Age ≥ 55 years\n  * Age ≤ 55 years and amenorrheic for 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression; or follicle stimulating hormone and estradiol in the postmenopausal range. Female participants of childbearing potential are eligible to participate if they agree to use a highly effective method of contraception that has a low user dependency consistently and correctly.\n\nNote: The effects of neratinib on the developing fetus are unknown and endocrine therapy is contraindicated in pregnancy. For this reason and because teratogenic effects have been observed in nonclinical studies and neratinib, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of the study participation, and for 1 month after the last dose of study medication. Should a woman become 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 3.5 months after completion of study treatment.\n\nExclusion Criteria:\n\n* Evidence of distant metastatic disease\n* Synchronous breast cancer that is estrogen receptor negative OR HER2-amplified OR requires treatment with neoadjuvant chemotherapy per the judgement of the treating physician\n* Patients harboring ineligible somatic HER2 mutations, such as those that are subclonal in nature or those resulting in the expression of truncated proteins including alterations that result in premature stop codon or a change in reading frame (ie, frame shift mutations).\n* Prior endocrine therapy for breast cancer within the last 2 years\n* Women who are pregnant, are planning to become pregnant, or are breast-feeding\n* Any investigational treatment for the current diagnosis of breast cancer\n* HER2 amplification by FISH (HER2:CEP17 ratio \\>2.0) or IHC (HER2 (3+)\n* Hepatic function impairment as defined by AST or ALT \\> 3x ULN OR total serum bilirubin \\> 1.5 (in patients with known Gilbert syndrome, a total bilirubin of \\> 3.0 x ULN or direct bilirubin \\> 1.5 x ULN)\n* Significant chronic gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn's disease, malabsorption, or Grade ≥2 National Cancer Institute \\[NCI\\] Common Terminology Criteria for Adverse Events Version 4.0 \\[CTCAE version 4.0\\] diarrhea of any etiology at baseline.\n* Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness\u002Fsocial situations that could, in the Investigator's judgment, make the patient inappropriate for this study.\n* Known hypersensitivity to any component of the investigational product, required combination therapy, or loperamide.\n* Unable or unwilling to swallow tablets.\n* Unable or unwilling to complete study procedures such as research biopsies or imaging\n* Any medical condition that in the judgement of the co-investigator would impair the patient's ability to complete the planned study therapy","18 Years",{"count":150,"type":21},30,[25],"This phase II trial tests how well neratinib prior to the primary treatment (neoadjuvant) works in treating patients with stage I-III HER2 mutated lobular breast cancers. Neratinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving neratinib in addition to normal therapy may work better in treating cancer than the endocrine therapy patients would normally receive.",[154,155,156,128],"Anatomic Stage I Breast Cancer","Anatomic Stage II Breast Cancer","Anatomic Stage III Breast Cancer","2026-08-17",{"date":159,"type":133},"2026-08-19",{"date":161,"type":133},"2024-06-11",{"date":163,"type":21},"2031-04-30",{"name":165,"class":140},"Vanderbilt-Ingram Cancer Center",5]