[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"UNICANCER\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":680},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,52,0,25,[9,46,75,105,137,162,194,219,247,275,307,333,359,380,410,437,461,488,512,532,559,584,604,632,653],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":16,"eligibilityCriteria":17,"healthyVolunteers":12,"sex":18,"minAge":19,"maxAge":20,"enrollmentInfo":21,"targetDuration":4,"studyType":24,"phases":25,"briefSummary":27,"conditions":28,"keywords":30,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":34,"lastUpdatePostDateStruct":35,"startDateStruct":38,"completionDateStruct":40,"leadSponsor":42,"locationsCount":45},"100620685","study-aiming-to-test-whether-non-invasive-liquid-biopsies-can-safely-reduce-invasive-surveillance-methods-in-lynch-syndrome-100620685",false,"NCT07360834","Study Aiming to Test Whether Non-invasive Liquid Biopsies Can Safely Reduce Invasive Surveillance Methods in Lynch Syndrome","Predicting Cancer Onset in Lynch Syndrome by Liquid Biopsies","PREDI-LYNCH","Inclusion Criteria:\n\n1. Participant must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.\n2. Age 35-80\n3. Genetically confirmed class 4-5 (likely pathogenic (LP) or pathogenic (P) variant, respectively) in MLH1, MSH2, MSH6, or EPCAM gene.\n4. The participant should be insurance covered for the financial costs of the standard surveillance and healthcare related to LS, such as affiliated to Social Security System\n\nExclusion Criteria:\n\n1. Previously performed proctocolectomy or equivalent (entire colon and rectum removed)\n2. Active treatment for cancer within 2 years prior to inclusion.\n3. Checkpoint inhibitor therapy within 12 months\n4. Pregnancy\n5. Participants unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.\n6. Persons deprived of their liberty or under protective custody or guardianship.","ALL","35 Years","80 Years",{"count":22,"type":23},2000,"ESTIMATED","INTERVENTIONAL",[26],"NA","Lynch syndrome is an inherited genetic predisposition that increases the risk of developing several types of cancer, particularly colon and rectal cancers (colorectal cancer), as well as cancer of the uterine lining (endometrial cancer). It affects around 1 in 400 people in Europe.\n\nToday, surveillance mainly relies on examinations such as colonoscopy (an examination of the colon using a camera) or gynaecological evaluations, sometimes accompanied by biopsies (the removal of a small tissue sample for microscopic analysis). Although effective, these procedures are invasive and demanding; they can affect quality of life and discourage some individuals from adhering to their recommended surveillance programme.\n\nThe European project PREDI-LYNCH is exploring an additional pathway that is simpler and better tolerated. This project relies on \"liquid biopsies\", meaning tests performed on easily collected samples such as blood, urine, stool, and vaginal swabs for women with a uterus. The PREDI-LYNCH study aims to determine whether these non-invasive tests could enable personalised surveillance and potentially increase the interval between more burdensome procedures, while maintaining a high level of medical safety.",[29],"Lynch Syndrome",[31,32],"Lynch Syndrome, hereditary cancer, MMR deficiency, Liquid biopsies, cancer early detection.","Lynch Syndrome, MMR deficiency, Liquid biopsies","NOT_YET_RECRUITING","2026-07-31",{"date":36,"type":37},"2026-08-03","ACTUAL",{"date":39,"type":23},"2026-12-01",{"date":41,"type":23},"2030-12-01",{"name":43,"class":44},"UNICANCER","OTHER",9,{"id":47,"slug":48,"hasResults":12,"nctId":49,"briefTitle":50,"officialTitle":51,"acronym":52,"eligibilityCriteria":53,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":55,"targetDuration":4,"studyType":24,"phases":57,"briefSummary":59,"conditions":60,"keywords":62,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":34,"lastUpdatePostDateStruct":68,"startDateStruct":69,"completionDateStruct":71,"leadSponsor":73,"locationsCount":74},"100619130","phase-2-clinical-trial-evaluating-the-biological-activity-of-a-new-drug-identified-as-prifetrastat-pf-07248144-combined-with-fulvestrant-for-the-treatment-of-patients-with-hormone-receptor-positive-hr-and-her2-negative-her2--breast-cancer-extended-to-other-organs-100619130","NCT07340619","Clinical Trial Evaluating the Biological Activity of a New Drug Identified as Prifetrastat (PF-07248144), Combined With Fulvestrant for the Treatment of Patients With Hormone Receptor Positive (HR+) and HER2 Negative (HER2-) Breast Cancer Extended to Other Organs.","UNLOCK - EPIBREAST, a Phase II Study of Prifetrastat (PF-07248144), a KAT6 Inhibitor, Plus Fulvestrant for Advanced HR+\u002FHER2- Breast Cancer, With Biomarkers Analyses","EPIBREAST","Inclusion Criteria:\n\nIn order to participate in the trial, all patients must meet all the following criteria:\n\n1. Patient must have signed the written informed consent prior to any study specific screening procedures.\n\n   Note : When the patient is physically unable to give her\u002Fhis written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.\n2. Adult participants age ≥18 years.\n3. Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer.\n4. Participants must have progressive disease after at least 1 prior line of a CDK4\u002F6 inhibitor and at least 1 prior line of endocrine therapy received in metastatic setting. Participants must not have received more than 3 prior lines of systemic therapies including up to 2 lines of cytotoxic chemotherapy for visceral disease in advanced or metastatic setting. Note that prior treatment with fulvestrant is permitted.\n5. Participants must have documentation of ER-positive tumor (≥10% positive stained cells) based on most recent tumor biopsy utilizing an assay consistent with local standards.\n6. Participants must have documentation of HER2-negative tumor: HER2-negative tumor is determined as immunohistochemistry score 0\u002F1+ or HER2 2+ and negative by in situ hybridization (FISH\u002FCISH\u002FSISH\u002FDISH) defined as a HER2\u002FCEP17 ratio \\\u003C2 or for single probe assessment a HER2 copy number \\\u003C4.\n7. Female participants with premenopausal status (see section 5.8.4) must be willing to undergo medically induced menopause by treatment with approved LHRH agonist such as goserelin, leuprolide or equivalent agents to induce chemical menopause.\n8. Participants must have at least 1 measurable lesion as defined by RECIST version 1.1 that has not been previously irradiated.\n9. Participants must present with a metastatic site easily accessible to a biopsy procedure and be a non-bone and non-irradiated site.\n10. ECOG Performance Status PS 0 or 1.\n11. Expected survival of more than 3 months.\n12. Adequate bone marrow function, including:\n\n    1. ANC ≥1,500\u002Fmm3 or ≥1.5 x 109\u002FL;\n    2. Platelets ≥100,000\u002Fmm3 or ≥100 x 109\u002FL;\n    3. Hemoglobin ≥9 g\u002FdL.\n13. Adequate renal function, including serum creatinine ≤1.5 x ULN or estimated creatinine clearance GFR ≥50 mL\u002Fmin as calculated using the method standard for the institution. In equivocal cases, a 24-hour urine collection test can be used to estimate creatinine clearance more accurately.\n14. Adequate liver function, including:\n\n    1. Total serum bilirubin ≤1.5 x ULN unless the participant has documented Gilbert syndrome;\n    2. AST and ALT ≤2.5 x ULN; AST and ALT ≤5.0 x ULN if there is liver involvement.\n15. Adequate blood clotting function: International Normalized Ratio (INR)\u002FProthrombin Time (PT) and either partial thromboplastin Time (PTT) or activated Partial Thromboplastin Time (aPTT) ≤1.5 x ULN.\n16. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1 except for AEs not constituting a safety risk by investigator judgment.\n17. Participants must consent to the use of their archived and\u002For collected tumor specimen, as well as blood samples, as detailed in the protocol, for future scientific research which includes, but is not limited to DNA, RNA, and protein-based biomarker detection.\n18. Women of childbearing potential must have a negative serum pregnancy test (with a sensitivity of at least 25 mIU\u002FmL) result within 3 days of enrolment.\n19. Men or women of childbearing potential must agree to the use of effective contraceptive for the study duration and for at least 28 days after the last dose of study treatment for women, and at least 93 days for men.\n20. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.\n21. . Patients must be affiliated to a Social Security System (or equivalent).\n22. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.\n\nExclusion criteria:\n\nPatients are not eligible to participate if they meet any of the following criteria:\n\n1. Participants with known symptomatic brain metastases requiring steroids. Participants 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 randomization, have discontinued corticosteroid treatment for these metastases for at least 3 weeks and are neurologically stable for 2 months (requires MRI confirmation).\n2. Participants with advanced\u002Fmetastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including participants with massive uncontrolled effusions \\[pleural, pericardial, peritoneal\\], pulmonary lymphangitis, and over 50% liver involvement). Note: Participants with indwelling catheter for drainage, or requirement for drainage no more frequently than once a month will be allowed.\n3. Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ. Other indolent cancers that do not interfere with assessment of primary cancer under study may be allowed with prior sponsor approval.\n4. Major surgery within 3 weeks prior to randomization.\n5. Radiation therapy within 3 weeks prior to randomization.\n6. Systemic anti-cancer therapy within 3 weeks prior to randomization. If the last immediate anti-cancer treatment contained an antibody-based agent(s) (approved or investigational), then an interval of 28 days or 5 half-lives (whichever is shorter) of the agent(s) prior to receive the study intervention treatment is required.\n7. Prior irradiation to \\>25% of the bone marrow.\n8. Participants with active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) HBV, HCV, known HIV or AIDS related illness. HIV seropositive subjects who are healthy and low risk for AIDS-related outcomes could be considered eligible.\n\n   Eligibility criteria for HIV-positive subjects should be evaluated and discussed with sponsor's medical monitor and will be based on current and past CD4 and T-cell counts, history (if any) of AIDS-defining conditions (eg, opportunistic infections), and status of HIV treatment. Also, the potential for drug-drug interactions will be taken into consideration. In equivocal cases, with positive serology, those participants with a negative viral load are potentially eligible provided the other entry criteria are met.\n9. Unmanageable ascites (limited medical treatment to control ascites is permitted, but all participants with ascites require review by sponsor's medical monitor).\n10. Baseline 12 -lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTc interval \\>470 msec, complete LBBB, signs of an acute myocardial infarction, ST changes suggestive of active myocardial ischemia, second- or third- degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is \\>470 msec, this interval should be rate corrected using the Fridericia method and the resulting QTcF- should be used for decision making and reporting. If QTcF exceeds 470 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the participant's eligibility. Computer -interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants. Cases must be discussed in detail with sponsor's medical monitor to judge eligibility.\n11. Any of the following in the previous 6 months: myocardial infarction, long QT syndrome, Torsade de Pointes, clinically important atrial or ventricular arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), serious conduction system abnormalities (eg, bifascicular block \\[defined as right bundle branch and left anterior or posterior hemiblock\\], 3rd degree AV block), unstable angina, coronary\u002Fperipheral artery bypass graft, symptomatic CHF, New York Heart Association class III or IV, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, and\u002For other clinical significant episode of thrombo embolic disease and ongoing cardiac dysrhythmias of NCI CTCAE ≥Grade 2. For Grade 2 atrial fibrillation, may be considered eligible with sponsor approval (e.g if improved to Grade 1 with non-urgent medical intervention or chronic Grade 2 atrial fibrillation with good rate control with non-urgent medical intervention). If a participant has a cardiac rhythm device\u002Fpacemaker placed and QTcF \\>470 msec, the participant can be considered eligible. Participants with cardiac rhythm device\u002Fpacemaker must be discussed in detail with sponsor's medical monitor to judge eligibility.\n12. Therapeutic anticoagulation.\n13. Hypertension that cannot be controlled by optimal medical therapy (eg, ≥160\u002F100 mmHg).\n14. Participation in other studies involving investigational drug(s) within 3 weeks prior to study entry. Participation in observational or in long term follow-up of other studies is allowed if no procedures which may interfere with the interpretation of study results will be performed.\n15. Known or suspected hypersensitivity or severe allergy to active ingredient\u002Fexcipients of study drug(s) such as lactose.\n16. Prior treatment with prifetrastat. Note that prior treatment with fulvestrant is permitted.\n17. Active inflammatory GI disease, refractory and unresolved chronic diarrhea or previous gastric resection, lap band surgery or other GI conditions and surgeries that may significantly alter the absorption of prifetrastat. Gastroesophageal reflux disease under treatment is allowed.\n18. Current use or anticipated need for food or drugs that are known moderate or strong CYP3A4\u002F5 inhibitors, including their administration within 10 days or 5 half-lives of the CYP3A4\u002F5 inhibitor, whichever is longer prior to first dose of study intervention (see Appendix 8 for a list of exemplary strong\u002Fmoderate CYP3A4\u002F5 inhibitors).\n19. Current use or anticipated need for food or drugs that are known strong CYP3A4\u002F5 inducers, including their administration within 10 days or 5 half-lives of the CYP3A4\u002F5 inducer, whichever is longer prior to the first dose of study intervention (see Appendix 8 for a list of exemplary strong\u002Fmoderate CYP3A4\u002F5 inducers).\n20. Current use or anticipated need for food or drugs that are known moderate\u002Fstrong CYP2C9 inhibitors, including their administration within \\[10 days or 5 half-lives of the CYP2C9 inhibitor, whichever is longer\\] prior to first dose of investigational product (amiodarone, fluconazole, miconazole, oxandrolone) (see Appendix 8 for a list of exemplary strong\u002Fmoderate CYP2C9 inhibitors).\n21. Current use or anticipated need for drugs that are known moderate\u002Fstrong CYP2C9 inducers, including their administration within \\[10 days or 5 half-lives of the CYP2C9 inducer, whichever is longer\\] prior to the first dose of investigational product (carbamazepine, rifampin) (see Appendix 8 for a list of exemplary strong\u002Fmoderate CY2C9 inducers).\n22. Patient is currently pregnant, breastfeeding, or planning to become pregnant.\n23. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation\u002Fbehavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.\n24. Patient unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.\n25. Person deprived of their liberty or under protective custody or guardianship.","18 Years",{"count":56,"type":23},51,[58],"PHASE2","Although treatments for breast cancer have improved, 20-30% of patients with early disease develop metastases (cancer that spreads to other parts of the body). Among the different types of breast cancer, hormone-sensitive cancers that do not overexpress the HER2 protein (HR+\u002FHER2-) are the most common. For patients with this type of cancer, an endocrine treatment such as aromatase inhibitors, tamoxifen or fulvestrant, is often used and may be combined with drugs called CDK4\u002F6 inhibitors, which help improve survival rate. However, when the cancer becomes resistant to these treatments, treatment strategies are more limited\n\nA new drug, prifetrastat (PF-07248144), which targets KAT6 proteins, which play a role in the growth of cancer cells, has shown promising results. Indeed, associated with fulvestrant, it allowed to fight against cancer in some patients who had already received many treatments.\n\nThe UNLOCK-EPIBREAST study aims to investigate whether the combination of prifetrastat plus fulvestrant could offer a new therapeutic option for people with HR+\u002FHER2- metastatic breast cancer who have already received endocrine therapy plus CDK4\u002F6 inhibitors.",[61],"Metastatic (Stage IV) Melanoma",[63,64,65,66,67],"Epiddrug","breast cancer RH+ \u002FHER2-","KAT6 inhibitor","prifetrastat","PF-07248144",{"date":36,"type":37},{"date":70,"type":23},"2026-09-18",{"date":72,"type":23},"2029-11-18",{"name":43,"class":44},8,{"id":76,"slug":77,"hasResults":12,"nctId":78,"briefTitle":79,"officialTitle":80,"acronym":81,"eligibilityCriteria":82,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":83,"targetDuration":4,"studyType":24,"phases":85,"briefSummary":86,"conditions":87,"keywords":91,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":34,"lastUpdatePostDateStruct":98,"startDateStruct":99,"completionDateStruct":101,"leadSponsor":103,"locationsCount":104},"100604597","phase-2-testing-two-different-drugs-sacituzumab-govitecan-and-trastuzumab-deruxtecan-combinations-prescribed-in-an-alterning-pattern-to-patients-with-metastatic-or-locally-advanced-triple-negative-breast-cancer-100604597","NCT07151586","Testing Two Different Drugs (Sacituzumab-govitecan and Trastuzumab-deruxtecan) Combinations Prescribed in an Alterning Pattern to Patients With Metastatic or Locally Advanced Triple-negative Breast Cancer","A Phase 2, Multicenter, Randomized, Open-label Trial Assessing Sacituzumab-govitecan and Trastuzumab-deruxtecan Combinations in an Alternating Regimen for Patients With Metastatic or Locally Advanced HER2-low Triple-negative Breast Cancer","ALTER","Inclusion Criteria:\n\n* Patient must have signed a written informed consent prior to any trial specific procedures. (Note : When the patient is physically unable to give his\u002Fher written consent, a impartial witness of their choice, independent from the investigator or the sponsor, can confirm in signing the patient's consent)\n* Men or women ≥ 18 years of age\n* Histologically confirmed metastatic or locally advanced and unresectable triple-negative breast cancer, meeting both of the following criteria by local testing:\n\nHER2-low breast cancer, defined as either immunohistochemistry (IHC) 2+ \u002F in situ hybridization (ISH)-negative or IHC 1+ (ISH-negative or untested), on either the primary or any metastatic site\n\nEstrogen receptor (ER) expression \\\u003C10% and progesterone receptor (PR) expression \\\u003C10% (Note: In case of bilateral breast cancer, participation in the study is permitted as long as both tumours correspond to a triple-negative breast cancer meeting the above criteria)\n\n* Patient eligible to receive sacituzumab-govitecan and T-Dxd according to their indication\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤1\n* Women of childbearing potential and male patients must agree to use adequate contraception for the duration of trial participation and up to 7 months after completing treatment for women and up to 4 months for men.\n\nA woman is considered to be of childbearing potential if she is not postmenopausal or has not undergone hysterectomy. Postmenopausal is defined as any of the following:\n\nAge ≥ 60 years Age \\\u003C 60 years and ≥ 12 continuous months of amenorrhea with no identified cause other than menopause Surgical sterilization (bilateral oophorectomy)\n\n\\- Adequate organ and bone marrow function within 28 days before enrollment. The most recent results available must be used for all parameters below:\n\nHemoglobin ≥ 9 g\u002FdL. Red blood cell transfusion is not allowed within 1 week prior to screening assessment\n\nAbsolute neutrophil count (ANC) ≥ 1,500\u002Fmm³. Granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment\n\nPlatelet count ≥ 100,000\u002Fmm³. Platelet transfusion is not allowed within 1 week prior to registration\n\nTotal bilirubin ≤ 1.5 × upper limit of normal (ULN) if no liver metastases, or \\\u003C 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastasis at baseline\n\nAlanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN, or \\\u003C 5 × ULN in patients with liver metastasis\n\nSerum albumin ≥ 2.5 g\u002FdL\n\nCreatinine clearance (CrCl) ≥ 30 mL\u002Fmin, calculated using the Cockcroft-Gault equation: CrCl (mL\u002Fmin) = \\[(140 - age in years) × weight in kg\\] \u002F \\[72 × serum creatinine in mg\u002FdL\\] (× 0.85 for females)\n\n* Adequate cardiac function, defined as a left ventricular ejection fraction ≥ 55% estimated by echocardiogram or multigated acquisition scintigraphy\n* Women of childbearing potential must have a negative serum or urine pregnancy test done within 7 days before randomization\n* Affiliated to the French Social Security System (or equivalent)\n* Patient willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.\n\nExclusion Criteria:\n\n* Patient previously treated with any ADC targeting HER2 or TROP2\n* Patient with uncontrolled or significant cardiovascular disease\n* Patients with brain metastases (BM) except for asymptomatic treated BM not requiring ongoing corticosteroid treatment with stable lesions on baseline\u002Fscreening brain MRI. Patients who require treatment of brain metastases are eligible after 14 days post surgery or radiation, if felt to be clinically stable and not requiring ongoing corticosteroid treatment\n* History of (non-infectious) interstitial lung disease (ILD)\u002Fpneumonitis that required steroids, or current ILD\u002Fpneumonitis, or suspected ILD\u002Fpneumonitis that cannot be ruled out by imaging at screening\n* Any medical history or condition that per protocol or in the opinion of the investigator is incompatible with the study\n* Patients with known allergy or severe hypersensitivity to any of the trial drugs or their excipients\n* Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may cause misleading study interpretation or prevent completion of study procedures and followup examinations\n* Patients with any other disease or illness that requires hospitalisation or is incompatible with the trial treatment are not eligible\n* Patients enrolled in another therapeutic trial within 30 days of inclusion\n* Pregnant or breast-feeding women at the time of randomization or intention to become pregnant during the study and up to 7 months after treatment\n* Person deprived of their liberty or under protective custody or guardianship\n* Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons",{"count":84,"type":23},260,[58],"This is a phase II, multicentre, open-label, randomised controlled trial (patients are randomly assigned to one treatment arm or the other) evaluating two treatment strategies (sacituzumab govitecan and trastuzumab deruxtecan in an alternative schema or sacituzumab govitecan alone) in patients with locally advanced or metastatic triple-negative breast cancer.\n\nThe goal is to answer the question: Does alternating sacituzumab goveitecan (SG) and trastuzumab deruxtecan (T-DXd) improve survival in patients with HER2-low metastatic triple-negative breast cancer compared to continuing treatment with SG alone?",[88,89,90],"Triple Negative Breast Neoplasms","Neoplasm Metastasis","HER 2 Low-expressing Breast Cancer",[92,93,94,95,96,97],"Antibody-drug conjugates","HER2-low","Triple Negative Breast Cancer","Locally Advanced Breast Cancer","HER2-negative","Metastatic Breast Cancer",{"date":36,"type":37},{"date":100,"type":23},"2026-09",{"date":102,"type":23},"2029-10",{"name":43,"class":44},2,{"id":106,"slug":107,"hasResults":12,"nctId":108,"briefTitle":109,"officialTitle":110,"acronym":111,"eligibilityCriteria":112,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":113,"targetDuration":4,"studyType":24,"phases":115,"briefSummary":116,"conditions":117,"keywords":123,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":34,"lastUpdatePostDateStruct":130,"startDateStruct":131,"completionDateStruct":133,"leadSponsor":135,"locationsCount":136},"100473299","targeted-therapy-drug-monitoring-in-digestive-oncology-100473299","NCT05443087","TARGETed Therapy Drug MONITOring in DIGestive Oncology","Dosing of Various Multi Kinases Inhibitors Plasma Concentrations for Patients Treated for Their Advanced Digestive Cancer, With the Aim to Determine the Best Optimal Dose for Each Treatment, in the Future","TARGETMONITO","Inclusion Criteria:\n\n1. Patient aged 18 years or over\n2. Advanced digestive cancer (histologically confirmed or confirmed by imaging for HCC) for which a standard treatment (according to each drug SmPC and as per standard of care) planned with:\n\n   * Regorafenib for GIST, mCRC, and HCC,\n   * Everolimus for gepNET,\n   * Sunitinib for pNET or GIST,\n   * Cabozantinib for HCC,\n   * Encorafenib - cetuximab for mCRC\n3. Life expectancy of greater than 3 months - at the discretion of the investigator\n4. Measurable disease according to tumor evaluation criteria as per local practice (Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, etc.)\n5. Patients must be affiliated to a Social Security System (or equivalent)\n6. Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.\n\nExclusion Criteria:\n\n1. Other concomitant anticancer systemic treatment (chronic chemotherapy, antitumor hormone therapy or immunotherapy) than the one studied\n2. Unresolved toxicity higher than NCI-CTCAE v5.0 Grade 1 attributed to any prior therapy\u002Fprocedure excluding alopecia and peripheral neuropathy\n3. Prior treatment with the same MKI molecule(s) planned to be given in the cohort. If different MKI molecules (from the one(s) planned in the study) have been previously taken, a wash out period of 2 weeks before treatment should be observed.\n4. Other invasive malignancies either currently active or active in the last 3 years, except adequately treated in situ carcinoma of the cervix and basal or squamous cell carcinoma of the skin\n5. Any condition that may jeopardize patient participation in the study as well as non contraception for male and female with child-bearing potential, pregnancy or breast feeding.\n6. Patient unwilling or unable to comply with the medical follow-up required by the standard treatment taken (including PK sampling during treatment phase and vital status collection during follow-up phase) because of psychosocial, familial, social or geographical reasons\n7. Participation in another clinical study with an investigational medicinal product during the last 30 days prior to inclusion and during the present study (except if patient is included in the control arm, with placebo or with a product which have a marketed authorisation, used as per the SmPC for the given indication)\n8. Patient deprived of their liberty or under protective custody or guardianship",{"count":114,"type":23},330,[26],"Targeted therapy drug monitoring in digestive oncology: Dosage of plasma levels of various multikinase inhibitors (MKI) in patients treated for advanced digestive cancer (gastrointestinal stromal tumor (GIST), metastatic colorectal cancer (mCRC), hepatocellular carcinoma (HCC), gastroenteropancreatic neuroendocrine tumor (gepNET), or pancreatic neuroendocrine tumor (pNET)), with the aim of determine the optimal dose adapted for each patient, in the future.",[118,119,120,121,122],"Digestive Cancer","Metastatic Colorectal Cancer","Hepatocellular Carcinoma","GIST","Neuroendocrine Tumors",[124,125,126,127,128],"multi kinases inhibitors","therapeutic drug monitoring","pharmacokinetics","pharmacodynamics","advanced digestive cancers","RECRUITING",{"date":36,"type":37},{"date":132,"type":37},"2022-08-29",{"date":134,"type":23},"2027-06",{"name":43,"class":44},29,{"id":138,"slug":139,"hasResults":12,"nctId":140,"briefTitle":141,"officialTitle":142,"acronym":143,"eligibilityCriteria":144,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":145,"targetDuration":4,"studyType":24,"phases":147,"briefSummary":148,"conditions":149,"keywords":151,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":155,"lastUpdatePostDateStruct":156,"startDateStruct":157,"completionDateStruct":159,"leadSponsor":161,"locationsCount":4},"100615578","phase-2-antibody-based-pet-imaging-and-treatment-response-in-breast-cancer-treated-with-an-antibody-drug-conjugate-100615578","NCT07294430","Antibody-based PET Imaging and Treatment Response in Breast Cancer Treated With an Antibody-drug Conjugate.","Antibody-based PET Imaging and Treatment Response in Breast Cancer Treated With an Antibody-drug Conjugate According to Current Standard Indications.","OASISImmunoPET","Inclusion Criteria:\n\n1. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent;\n2. Patients enrolled in the prospective cohort of the OASIS study;\n3. Patient with locally advanced or metastatic breast cancer eligible to receive T-DXd as part of their standard care;\n4. At baseline imaging at least two \"target\" lesions fulfilling the following criteria: (1) anatomically transaxial diameter ≥ 1.5 cm and measurable per RECIST1.1. and (2) metabolically assessable with a maximum standard uptake value corrected for lean body mass (SUVmax) ≥ 1.5 x SUVmean + 2 standard deviations (SD) of the liver measured in a 3-cm-diameter spherical volume of interest (VOI) in normal liver parenchyma;\n5. Patients must be willing and able to comply with the protocol for the duration of the trial;\n\nExclusion Criteria:\n\n1. Patients already treated with Trastuzumab deruxtecan (T-DXd);\n2. Hypersensitivity at the ImmunoPET radioligands injection;\n3. Patients who are claustrophobic or unable to remain still for 30 minutes;\n4. Female participant who is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 90 days after the final administration of study treatment;\n5. Person deprived of their liberty or under protective custody or guardianship.",{"count":146,"type":23},30,[58],"OASIS-ImmunoPET is a monocentric pilot study evaluating antibody imaging to predict response to antibody-drug conjugate (ADC), an innovative cancer targeted therapy, and potentially replace tumor biopsy. It is addressed to patients with locally advanced or metastatic breast cancer who are eligible to receive the ADC Trastuzumab deruxtecan (T-DXd) according to local approval, and who are already enrolled in OASIS study (NCT pending).",[150],"Locally Advanced or Metastatic Breast Cancer",[152,153,154],"Advanced molecular imaging","ADC","Response","2026-07-30",{"date":34,"type":37},{"date":158,"type":23},"2026-12-31",{"date":160,"type":23},"2030-12-31",{"name":43,"class":44},{"id":163,"slug":164,"hasResults":12,"nctId":165,"briefTitle":166,"officialTitle":167,"acronym":168,"eligibilityCriteria":169,"healthyVolunteers":12,"sex":170,"minAge":19,"maxAge":171,"enrollmentInfo":172,"targetDuration":4,"studyType":24,"phases":174,"briefSummary":176,"conditions":177,"keywords":181,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":155,"lastUpdatePostDateStruct":187,"startDateStruct":188,"completionDateStruct":190,"leadSponsor":192,"locationsCount":193},"100601141","phase-3-optimising-adjuvant-chemotherapy-prescription-in-young-patients-with-hormone-dependent-breast-cancer-using-genomic-tests-100601141","NCT07106632","Optimising Adjuvant Chemotherapy Prescription in Young Patients With Hormone-dependent Breast Cancer Using Genomic Tests","Optimal Personalized Treatment of Early Breast Cancer Using Multi-parameter Analysis: Focus on YOUNGer Women","OPTIMA-YOUNG","Inclusion Criteria:\n\n1. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in signing the patient's consent;\n2. . Premenopausal defined by patient that are not post-menopaused\n3. Female\n4. Age ≥ 35 years\n5. Diagnosis of invasive HR-positive (ER≥10% of tumour cells stained positive and any PR expression) HER2-negative (IHC score 0-1+ or 2+ with negative\u002Fnon-amplified ISH) invasive breast cancer; ER and HER2 determination will be assessed according to latest ASCO\u002FCAP or national guidelines;\n6. Breast and axillary surgery completed ≤ 12 weeks from study entry and randomization;\n7. Availability of a Formalin-Fixed Paraffin-Embedded (FFPE) tumour sample from surgery to perform Prosigna® analysis or slides.\n\n   Note: in case of receipt of neoadjuvant endocrine therapy the Prosigna® test must be done on the baseline biopsy. Performing the test on the surgical piece or on on-treatment biopsy is not permitted.\n8. Tumour size and axillary lymph node status. One of the following must apply:\n\n   1. 1-3 lymph nodes involved AND any invasive tumour size.\n   2. node negative (including micrometastases in at least 1 node \\[i.e. deposit \\>0.2-2mm diameter\\]) AND invasive tumour size ≥ 50mm.\n9. Multiple ipsilateral breast cancers are permitted provided that at least one tumour meets the tumour size and axillary lymph node entry criteria, and none meet any of the exclusion criteria.\n10. Bilateral breast cancers are permitted provided the tumour(s) in one breast meets the eligibility criteria and the other, contralateral tumour is not ER negative and\u002For HER2 positive and not clinically significant, defined by both of the following:\n\n    1. The contralateral tumour does not fulfil the tumour size and lymph node eligibility criteria required for trial entry; i.e. the following are not acceptable:\n\n       .i. presence of lymph node macro-metastases; .ii. tumour size ≥50mm when there is no lymph node involvement.\n    2. The treating physician does not consider that the characteristics of the contralateral tumour alone justify consideration of adjuvant chemotherapy.\n11. Fitness to receive adjuvant chemotherapy, as judged by the treating physician;\n12. Short term pre-surgical treatment with endocrine therapy, including in combination with non-cytotoxic agents, is allowed providing that the duration of treatment did not exceed 8 weeks;\n13. Patients affiliated with or a beneficiary of the local social security system, health social security system, or other local regulatory requirements\n14. Patients must agree to use adequate contraception methods for the duration of study treatment and for the duration specified in the SmPC after completing the treatment, unless agreed with the treatment physician the safety of attempt a pregnancy, which could be possible after at least 18 months of endocrine therapy.\n\nNote : patient with extracapsular nodular transgression are eligible. NOTE: If neoadjuvant endocrine therapy was received, the Prosigna® test must be realized on the baseline biopsy. Performing the test on the surgical specimen or on biopsy taken during treatment is not permitted.\n\nNOTE: Re-excision or complementary mastectomy for close\u002Fpositive surgical margins should be postponed after chemotherapy completion, if chemotherapy is given; breast reconstruction is allowed after trial entry.\n\nNOTE: The use of approved adjuvant targeted agents (abemaciclib, ribociclib and olaparib) combined to adjuvant endocrine therapy is allowed according to local practice recommendations and availability.\n\nExclusion Criteria:\n\n* 1\\. Postmenopausal women. Women who fulfil the following criteria at trial entry will be considered postmenopausal:\n\n  1. Age \\>45 and natural amenorrhoea of at least 1 year's duration.\n  2. Bilateral surgical oophorectomy.\n  3. For amenorrhoea not fulfilling the above criteria the diagnosis of postmenopausal status should be supported by hormone measurement: FSH levels must be \\> 25IU\u002FL with low oestradiol (i.e. within the locally defined postmenopausal range), in the event of doubt measured on 2 occasions preferably 4-6 weeks apart. This applies to women who have undergone hysterectomy without bilateral surgical oophorectomy and are age \\\u003C60; those ≥60 may be considered postmenopausal.\n\n     NOTE: Hormonal contraception will suppress FSH and oestradiol levels. In those taking oral contraception, levels will recover rapidly on discontinuation. Depo-Provera injectable contraception lasts many months: all women receiving this agent should be considered premenopausal.\n\n     2\\. Stage IV breast cancer; 3. Start of adjuvant systemic treatment (except for neoadjuvant endocrine therapy for a duration ≤ 8 weeks) before trial entry\\*; 4. Previous diagnosis of malignancy except:\n\n  \u003C!-- -->\n\n  1. Previous ductal carcinoma in situ (DCIS) or pleomorphic lobular carcinoma in situ (LCIS) of the breast managed by local treatment only;\n  2. Previous in situ carcinoma as defined by the International Classification of Diseases for Oncology (ICD-O) including basal cell carcinoma of skin and cervical intraepithelial neoplasia;\n  3. Previous invasive malignancy managed by local treatment only AND disease-free for at least 10 years.\n\n     5\\. Patients enrolled in another therapeutic trial within 30 days of inclusion; 6. Presence of concomitant medical and\u002For psychiatric comorbidities and\u002For social problems that might prevent informed consent, treatment compliance or follow up; 7. Person deprived of their liberty or under protective custody or guardianship.\n\n     8\\. Pregnant women or women who are breast-feeding at inclusion. 9. Patients unwilling or unable to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures because of geographic, familial, social, or psychological reasons.\n\n     \\*Trial entry is dated from of the date the participant signs the consent form or provides remote verbal consent, whichever is earlier.","FEMALE","45 Years",{"count":173,"type":23},3380,[175],"PHASE3","Rationale:\n\nAround 70 to 80% of breast cancers are so-called \"hormone-dependent\" (HR+)\u002FHER2-. For more than 50 years, studies have shown that chemotherapy and optimised hormonal treatments (hormone therapy), including a drug associated with ovarian suppression (OFS), improve survival in patients with these cancers, which are characterised by a high risk of relapse. However, younger patients suffer more side effects than older women, particularly from chemotherapy. This can affect their quality of life and reduce their ability to work.\n\nFor post-menopausal women, genetic tests exist to assess whether chemotherapy is really necessary in addition to hormonal treatment. However, for high-risk premenopausal patients, chemotherapy is still systematically recommended, as no study has proved that it can be safely avoided. Clinical trials based on risk stratification using genetic tests have not been conclusive, but the majority of premenopausal women included had not received optimal hormone treatment. It is possible that the beneficial effect of chemotherapy is partly due to the artificial menopause it induces. Some experts believe that, for patients with a high clinical risk but a low genetic risk, an optimised hormonal treatment (drug + OFS) could suffice, without the need for chemotherapy.\n\nObjectives:\n\nMain objective: The aim of the study is to determine whether the use of a genetic test (Prosigna®) to decide whether or not to administer chemotherapy produces results as good as standard treatment (systematic chemotherapy) in premenopausal women with hormone-dependent (HR+) breast cancer\u002FHER2-, by assessing their risk of cancer recurrence.\n\nThe secondary objectives include verifying whether, in patients with a low Prosigna® score (around 70% of cases), optimised hormonal treatment (including suppression of ovarian function) is as effective as chemotherapy combined with hormonal in treatment preventing cancer recurrence. The study also seeks to compare the efficacy of treatment Prosigna®-guided versus systematic chemotherapy in terms of recurrence and quality of life, as well as economic aspects. Finally, the aim is to understand patients' concerns about the concept of reducing treatment (therapeutic de-escalation) and the way in which this information is communicated to them.\n\nThe primary endpoint of the study is to measure the time elapsed between the start of participation in the study and the appearance of an event indicating a return of the cancer. This includes the return of cancer in the same breast or neighbouring areas, the spread of cancer to other parts of the body, the appearance of new cancer in the other breast or death from any cause.\n\nTrial Population:\n\nThe study includes women major premenopausal diagnosed with invasive, hormone receptor-positive (ER+) and HER2-negative breast cancer. Patients must have undergone breast and axillary surgery recent and have a tumour sample suitable for analysis by the testProsigna® . They must be able to receive the study treatments Postmenopausal women, women with stage IV breast cancer, women who have already received adjuvant systemic treatment (except short neoadjuvant hormone therapy), women with a recent history of invasive cancer, pregnant women or women who are breast-feeding will not be able to take part in the study.\n\nInterventions:\n\nAfter agreeing to take part, patients will enter the pre-inclusion period (up to 28 days before randomisation), during which the investigator will carry out all the necessary tests to assess their eligibility. The investigator will then randomise the patients to find out which treatment they have been assigned, no more than 2 weeks later: the experimental group will receive a treatment decided on the basis of the results of a genomic test: either chemotherapy and hormone therapy, or hormone therapy alone. The control group will receive the standard treatment. The treatment and follow-up phases are the same as for standard care. Information on the quality of life patient's will and other information (associated costs, perception of their participation in the study, etc.) also be collected by means of questionnaires completed by the patients during the 5 years following randomisation.",[178,179,180],"Early Breast Cancer","Premenopausal Breast Cancer","HR+\u002FHER2- Breast Cancer",[182,183,184,185,186],"Adjuvant therapy de-intensification","Care delivery","Quality of Life","Premenopausal Women","Risk stratification",{"date":34,"type":37},{"date":189,"type":37},"2026-06-26",{"date":191,"type":23},"2038-08-15",{"name":43,"class":44},105,{"id":195,"slug":196,"hasResults":12,"nctId":197,"briefTitle":198,"officialTitle":199,"acronym":200,"eligibilityCriteria":201,"healthyVolunteers":12,"sex":202,"minAge":54,"maxAge":20,"enrollmentInfo":203,"targetDuration":4,"studyType":24,"phases":205,"briefSummary":206,"conditions":207,"keywords":210,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":155,"lastUpdatePostDateStruct":212,"startDateStruct":213,"completionDateStruct":215,"leadSponsor":217,"locationsCount":218},"100564191","phase-3-study-evaluating-the-efficacy-and-safety-of-darolutamide-and-stereotactic-dose-escalated-radiotherapy-in-patients-with-localized-prostate-cancer-and-high-risk-features-of-relapse-100564191","NCT06625970","Study Evaluating the Efficacy and Safety of Darolutamide and Stereotactic Dose Escalated Radiotherapy in Patients With Localized Prostate Cancer and High-risk Features of Relapse","A Randomized Phase III Trial With a Factorial Design Evaluating the Efficacy and Safety of Darolutamide and Stereotactic Dose Escalated Radiotherapy in Patients With Localized Prostate Cancer and High-risk Features of Relapse, From the Prostate Cancer Consortium in Europe (PEACE)","PEACE 7","Inclusion Criteria:\n\n1. Signed a written informed consent form prior to any trial specific procedures\n\n   Note: In case of physical incapacitation, a trusted representative of their choice, which is not the investigator or sponsor, can sign on the behalf of the patients\n2. Men, 18 years ≤ Age ≤ 80 years\n3. ECOG performance status of 0 or 1\n4. No significant co-morbidities that might prevent long-term follow-up\n5. Histologically confirmed adenocarcinoma of the prostate\n6. Meet at least 2 of the following criteria from NCCN classification:\n\n   * Gleason score ≥8\n   * T3 or T4 disease (T3 defined by MRI is acceptable)\n   * Prostate-specific antigen ≥20 ng\u002FmL\n7. Prostate size on MRI \\\u003C100 cc\n8. Absolute neutrophil count ≥ 1.5 x 10⁹\u002FL\n9. Platelet count ≥100 x 10⁹\u002FL\n10. Haemoglobin ≥90 g\u002FL (in absence of red blood cell transfusion within 4 weeks prior to randomization)\n11. Hepatic function: serum alanine aminotransferase (ALT) and\u002For aspartate transaminase (AST) ≤2.5 x upper limit of normal (ULN), total bilirubin ≤1.5 x ULN\n12. Creatinine ≤2.0 x ULN\n13. Sexually active patients must agree to use an effective contraceptive method while on treatment and for 1 week after the final dose of investigational product\n14. Patient must be affiliated to a Social Security System or in possession of equivalent private health insurance (according to local regulations for participation in clinical trials)\n15. Patient must be willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up\n\nExclusion Criteria:\n\n1. Clinically or radiologically detectable metastasis, including no evidence of pelvic lymph node metastasis on next generation imaging (PSMA PET\u002FCT), nor enlarged pelvic lymph nodes (≥1 cm in small diameter) on MRI Note: Patients with infra-centimetric nodal disease (\\\u003C1 cm in small diameter) on conventional imaging and equivocal hyperfixation on next generation imaging may be included\n2. Recent history of TURP or prostate enucleation (less than 6 months) Note: patients with severe obstructive symptoms (defined as International Prostate Symptom Score (IPSS) ≥20) should be carefully evaluated to rule out the need for TURP\u002FProstate enucleation\n3. Prior treatment for prostate cancer, including prostatectomy, except lymph node dissection (patients with PN- disease only can be accrued) or ADT (started more than 6 weeks before randomization)\n4. Patient with other known concurrent severe and\u002For uncontrolled concurrent medical disease or infection (such as active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease) or co-morbidity, which could compromise participation in the study\n5. Cardiac disease such as uncontrolled hypertension (systolic BP ≥160 mmHg or diastolic BP ≥95 mmHg; 3 consecutive measures taken 5 minutes apart), stroke, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, coronary\u002Fperipheral artery bypass graft, LVEF \\> grade 2\n6. Uncontrolled diabetes mellitus\n7. Current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, stable chronic liver disease per investigator assessment)\n8. Gastrointestinal disorder or procedure, which expects to interfere significantly with absorption of study treatment. Severe GI disorders precluding pelvic irradiation\n9. Known severely impaired lung function (spirometry and DLCO 70% or less of normal and O2 saturation of 88% or less at rest on room air)\n10. Other prior malignancy within the last 3 years, except basal cell skin cancer\n11. Known hypersensitivity to the study treatment or any of its ingredients.\n12. Physical or psychological condition or any condition that in the opinion of the investigator would impair the patients' ability to comply with the study procedures\n13. Previous treatment for prostate cancer (surgery or radiotherapy) or previous pelvic irradiation that would make prostate\u002Fpelvis radiotherapy impossible\n14. Concomitant prohibited treatment. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4\u002F5. A one-week washout period is necessary for patients who are already on these treatments\n15. Prior treatment with second generation androgen receptor (AR) inhibitors, other investigational AR inhibitors, or CYP17 enzyme inhibitor\n16. Use of oestrogens or 5-α reductase inhibitors or AR inhibitors\n17. Acute toxicities of prior treatments and procedures not resolved to grade ≤1 or baseline before randomization\n18. Prior chemotherapy or immunotherapy for prostate cancer\n19. Major surgery within 28 days before randomization\n20. Participation in another therapeutic trial within 30 days prior to inclusion\n21. Persons deprived of their liberty or under protective custody or guardianship\n22. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons","MALE",{"count":204,"type":23},700,[175],"PEACE 7 is an international, multicenter, randomized, open-label phase III study that aims at evaluating the efficacy and safety of darolutamide and of stereotactic dose escalated prostate radiotherapy in patients with localised prostate cancer and high-risk features of relapse (defined as patients with at least 2 high-risk criteria from National Comprehensive Cancer Network (NCCN) classification) using a factorial (2x2) design.\n\nThe primary objective of this study is to assess the efficacy of darolutamide and of a stereotactic dose escalated radiotherapy targeting prostate in combination with ADT and pelvic nodal radiotherapy in terms of metastasis-free survival (MSF).\n\nPatients will be randomized (1:1:1:1) to receive either:\n\n* Arm A (Standard arm): ADT + conventional fractionated or moderately hypo-fractionated prostate radiotherapy including pelvic nodal radiotherapy\n* Arm B (Experimental arm): ADT + conventional fractionated or moderately hypo-fractionated prostate radiotherapy including pelvic nodal radiotherapy + darolutamide\n* Arm C (Experimental arm): ADT + conventional fractionated or moderately hypo-fractionated pelvic nodal radiotherapy + Prostate SBRT\n* Arm D (Experimental arm): ADT + conventional fractionated or moderately hypo-fractionated pelvic nodal radiotherapy + Prostate SBRT + darolutamide\n\nPatient will receive systemic treatments (ADT and\u002For darolutamide) during 2 years where visits on site are planned at D45, D90, D180 and then every 3 months for checkups and follow prostate specific antigen (PSA) level.\n\nMetastasis-free survival (MFS) is defined as the time interval from randomization to the date of the appearance of metastasis (on next generation imaging) or death (from any cause), whichever occurs first. Radiographic evaluation will be carried out at the time of biochemical failure (Phoenix criteria) or in case of clinical suspicion. After biochemical failure (Phoenix criteria) radiographic evaluation on next generation imaging (prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scan (any European Medicines Agency (EMA) approved PSMA tracer)) will be performed every 6 months until a metastatic site of relapse is identified and will be repeated at each subsequent PSA progression.",[208,209],"High Risk Prostate Carcinoma","Prostate Cancer",[211],"HPRC, PSMA-PET, Prostate Cancer, High-Risk",{"date":34,"type":37},{"date":214,"type":37},"2025-04-10",{"date":216,"type":23},"2045-10",{"name":43,"class":44},6,{"id":220,"slug":221,"hasResults":12,"nctId":222,"briefTitle":223,"officialTitle":224,"acronym":225,"eligibilityCriteria":226,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":227,"targetDuration":4,"studyType":24,"phases":229,"briefSummary":230,"conditions":231,"keywords":233,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":155,"lastUpdatePostDateStruct":240,"startDateStruct":241,"completionDateStruct":243,"leadSponsor":245,"locationsCount":246},"100419847","phase-3-study-on-the-efficacy-of-treatment-by-radiotherapy-and-pembrolizumab-in-newly-diagnosed-metastatic-head--neck-cancers-100419847","NCT04747054","Study on the Efficacy of Treatment by Radiotherapy and Pembrolizumab in Newly Diagnosed Metastatic Head & Neck Cancers","Randomized Trial of Loco-regional Radiotherapy Added to Pembrolizumab Alone or With Chemotherapy Versus Systemic Treatment Alone for Patients With Newly Diagnosed Head and Neck Squamous Cell Carcinoma With Synchronous Metastases","PembroMetaRT","Inclusion Criteria:\n\n1. Patient must have signed a written informed consent form prior to any study specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.\n2. Histologically confirmed squamous cell carcinoma of head and neck (oral cavity, oropharynx, hypopharynx, and larynx) including unknown primary head and neck lymph nodes with distant metastases at presentation (T1-4 N0-3 M1). Histological confirmation is required in case of a single metastatic lesion.\n3. Eligible for treatment by pembrolizumab according to the European Marketing Authorization\n4. Patient ≥18 years old\n5. Performance status: 0-1 (WHO)\n6. Combined Positive Score (CPS) ≥1 for primary tumor (as determined per local practice)\n7. Subjects must have at least one measurable lesion as per RECIST v1.1 to assess efficacy\n8. Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to randomization:\n\n   a. If randomization is done before treatment start: i. Absolute neutrophil count ≥1.5 × 10⁹\u002FL ii. Platelet ≥100 × 10⁹\u002FL iii. Hemoglobin ≥90 g\u002FL iv. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT), ≤3 × upper limit of normal (ULN), (unless documented liver metastases where ≤5 x ULN is permitted) v. Bilirubin ≤1.5 × ULN. vi. Serum albumin ≥25 g\u002FL vii. Creatinine clearance ≥30 mL\u002Fmin (calculated per institutional guidelines or by Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formula) viii. Corrected serum calcium of ≤11.5 mg\u002FdL or ≤2.6 mmol\u002FL. b. If randomization if done after treatment start i. Absolute neutrophil count ≥1.0 × 10⁹\u002FL ii. Platelet ≥75 × 10⁹\u002FL iii. Hemoglobin ≥85 g\u002FL\n9. Patient must agree to use adequate contraception methods for the duration of the study treatment and up to 4 months after the last dose of pembrolizumab administration\n10. Patients must be affiliated to a Social Security System (or equivalent)\n11. No disease progression during systemic treatment if the randomization is done after the start of pembrolizumab for the current disease\n\nExclusion Criteria:\n\n1. Symptomatic central nervous system (CNS) metastases and \u002F or carcinomatous meningitis\n2. History of another malignancy within 2 years prior to study inclusion, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in-situ carcinoma\n3. Prior radiotherapy in the head and neck region\n4. Any prior or current non-surgical treatment for invasive head and neck cancer. (except for pembrolizumab +\u002F- chemotherapy for the current cancer for a maximum of 6 cycles). This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, chemotherapy, anti-PD-1\u002FPD-L1 and CTLA-4, prior radiotherapy (RT), or use of any investigational agent. Loco-regional recurrent or second primary head and neck cancer after prior surgical treatment alone in the head and neck region could be eligible.\n5. Known Acquired Immune Deficiency Syndrome (AIDS)\n6. Known currently active infection including hepatitis B or hepatitis C\n7. Patient having received live attenuated vaccine within 28 days prior to enrolment\n8. Pregnant or breast feeding woman\n9. Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, or psoriasis which do not require systemic treatment\n10. Active immunodeficiency or ongoing immunosuppressive therapy\n11. Active symptomatic interstitial lung disease\n12. Significant disease which, in the judgment of the investigator, as a result of the medical interview, physical examinations, or screening investigations would make the patient inappropriate for entry into the trial\n13. Any social, personal, medical, geographic and\u002For psychologic factor(s) that could interfere with the observance of the patient to the protocol and\u002For the follow-up and\u002For the signature of the informed consent\n14. Prior organ transplantation including allogenic stem-cell transplantation\n15. Other severe acute or chronic medical conditions including colitis, pneumonitis, pulmonary fibrosis or psychiatric conditions including active suicidal ideation; or laboratory abnormalities that may increase the risk associated with study participation and, in the judgment of the investigator, would make the patient inappropriate for entry into this study\n16. Person deprived of their liberty or under protective custody or guardianship\n17. Patient who have taken any investigational medicinal product or have used an investigational device within 30 days prior to study inclusion",{"count":228,"type":23},102,[175],"Study to evaluate the efficacy of treatment by radiotherapy and pembrolizumab in newly diagnosed metastatic head \\& neck cancers",[232],"Squamous Cell Carcinoma of Head and Neck",[234,235,236,237,238,239],"Metastatic","Radiotherapy","pembrolizumab","Squamous Cell Carcinoma","Head and Neck","Carcinoma",{"date":34,"type":37},{"date":242,"type":37},"2021-12-01",{"date":244,"type":23},"2029-10-01",{"name":43,"class":44},26,{"id":248,"slug":249,"hasResults":12,"nctId":250,"briefTitle":251,"officialTitle":252,"acronym":253,"eligibilityCriteria":254,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":255,"targetDuration":4,"studyType":24,"phases":257,"briefSummary":258,"conditions":259,"keywords":261,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":267,"lastUpdatePostDateStruct":268,"startDateStruct":270,"completionDateStruct":272,"leadSponsor":274,"locationsCount":4},"100650302","phase-3-investigating-precision-medicine-in-the-adjuvant-setting-in-biliary-tract-cancer-100650302","NCT07745296","Investigating Precision Medicine in the Adjuvant Setting in Biliary Tract Cancer","Investigating Precision Medicine in the Adjuvant Setting: a Phase 3 Clinical Trial in Biliary Tract Cancer","SAFIR-IMPACT","SCREENING PHASE\n\nInclusion Criteria:\n\n1. Signed a written informed consent form prior to any trial specific procedures (Consent #1)\n2. Histologically-proven intrahepatic cholangiocarcinoma, perihilar or distal extrahepatic cholangiocarcinoma or gallbladder carcinoma (ampullary carcinoma is excluded)\n3. Macroscopically complete resection of the primary tumour (R0 or R1 surgical margin status)\n4. Aged ≥18 years\n5. Affiliated to a social security system or in possession of equivalent private health insurance (according to local country health provision arrangements).\n\nExclusion Criteria:\n\n1. Contraindication to standard adjuvant therapy\n2. Prior anticancer therapy in the neoadjuvant or adjuvant setting.\n3. Patients with gallbladder cancer which has not extended to involve the muscle layers or lymph nodes (pT1aN0)\n4. Planned post-operative radiation therapy\n5. Prior treatment with any of the MTT under investigation in the trial\n6. Other invasive malignancies, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 3 years or more and are deemed at negligible risk for recurrence, are eligible for the trial\n7. Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol\n8. Women who are pregnant or breast-feeding\n9. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons\n10. Individuals deprived of liberty or placed under protective custody or guardianship\n\nRANDOMISED PHASE Inclusion criteria\n\n1. Signed a written informed consent form prior to any trial specific procedures (Consent #2)\n2. Molecular profile showing the tumour harbours at least one targetable molecular alteration with a MTT in the study portfolio (as determined by the trial MTB)\n3. Surgery performed at least four weeks prior to randomisation with adequate wound healing (in the Investigator's opinion) to allow adjuvant therapy to be initiated\n4. No measurable disease, as assessed by the investigator: normal post-operative thoracic, abdominal and pelvic CT scan or normal MRI of abdomen and pelvis + normal chest CT performed within 4 weeks prior to randomisation\n5. ECOG performance status of 0 or 1\n6. Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5 × 10⁹\u002FL, platelet count ≥100 × 10⁹\u002FL, and haemoglobin ≥9 g\u002FdL\n7. Adequate liver function: total bilirubin level ≤1.5 × the upper limit of normal (ULN) range (total bilirubin ≤3.0 ULN when the patient has documented Gilbert syndrome), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤2.5 × ULN\n8. Adequate renal function: estimated creatinine clearance ≥50 mL\u002Fmin according to the Cockcroft-Gault formula, or estimated glomerular filtration rate (eGFR) value ≥50 mL\u002Fmin using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation\n9. Men, and women of childbearing potential (WOCBP) must agree to use adequate contraception for the duration of trial participation and as required after completing study treatment. Men must also agree to not donate sperm and women must agree to not donate oocytes during the specified period.\n\n   Note: See Section 5.8.5 for a definition of adequate contraception and required duration of contraceptive use following treatment with individual MTTs.\n10. Women of childbearing potential must have a negative serum pregnancy test performed within 3 days before the date of randomisation\n11. Willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests, and other study procedures\n12. Affiliated to a social security system or in possession of equivalent private health insurance (according to local country health provision arrangements).\n\nExclusion criteria\n\n1. Disease relapse occurring at any time prior to randomisation\n2. Surgery performed more than 16 weeks prior to randomisation\n3. Previous adjuvant treatment, including any systemic treatment, or radiotherapy\n4. Inability or unwillingness to swallow pills\n5. History of malabsorption syndrome or other condition that would interfere with enteral absorption. For example, active intestine inflammation (e.g., Crohn's disease or ulcerative colitis) requiring immunosuppressive therapy\n6. Contraindication or known hypersensitivity to capecitabine or fluorouracil or to the MTT for the molecular alteration found in the patient, or any component in their formulation Note: For patients with multiple target alterations, contraindication to one MTT will not warrant exclusion if MTT to an alternative target is feasible.\n7. Radiotherapy within 7 days of randomisation\n8. History of severe and unexpected reactions to fluoropyrimidine therapy\n9. Known complete dihydropyrimidine dehydrogenase (DPD) deficiency\n10. Recent or concomitant treatment with brivudine\n11. History of myocardial infarction or unstable angina within 6 months prior to enrolment, troponin levels consistent with myocardial infarction, or clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension, or any history of symptomatic congestive heart failure.\n12. Patients with a heart-rate corrected QT interval (using Fridericia's formula) (QTcF) ≥ 450 msec or other factors that increased the risk of QT prolongation or arrhythmic events (e.g. heart failure, hypokalaemia, family history of long QT interval syndrome).\n13. Patients with HBV with HBV-DNA higher than 500IU\u002FmL, active untreated HCV infection, or HIV infection with CD4 below 200. Patients with controlled HBV, HCV and HIV infections are allowed.\n14. Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol\n15. Women who are pregnant or breast-feeding\n16. Participation in another therapeutic trial within the 30 days prior to entering the study (participation in an observational trial would be acceptable)\n17. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons\n18. Individuals deprived of liberty or placed under protective custody or guardianship\n\nADDITIONAL EXCLUSION CRITERIA FOR SPECIFIC MTTs:\n\nFutibatinib cohort\n\n1. History and\u002For current evidence of any of the following disorders:\n\n   1. Non-tumour related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator. Blood phosphate concentration should be ≤ ULN at baseline examination.\n   2. Ectopic mineralization\u002Fcalcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator\n   3. Retinal or corneal disorder confirmed by retinal\u002Fcorneal examination and considered clinically significant in the opinion of the Investigator\n2. Concomitant treatment with strong CYP3A\u002FP-gp inhibitors or strong or moderate CYP3A\u002FP gp inducers where these cannot be substituted for another therapy.\n\nIvosidenib cohort\n\n1. Patients with history of torsade de pointes\n2. Concomitant treatment with digoxin where this cannot be substituted for another therapy\n3. Concomitant treatment with strong CYP3A4 inducers or dabigatran where these cannot be substituted for another therapy\n4. Concomitant treatment with medicinal products known to prolong the QTc interval, or moderate or strong CYP3A4 inhibitors where these cannot be substituted for another therapy\n5. Familial history of sudden death or polymorphic ventricular arrhythmia\n6. Hypokalaemia, hypomagnesemia or hypocalcaemia where this cannot be corrected by supplementation\n\nZanidatamab cohort\n\n1. Total lifetime anthracycline load exceeding 360 mg\u002Fm2 Adriamycin® or equivalent.\n2. Use of corticosteroids administered at doses equivalent to \\>15 mg per day of prednisone within 2 weeks of first zanidatamab dosing unless otherwise approved by the coordinating investigator. Topical, ocular, intra-articular, intranasal, and\u002For inhalational corticosteroids are permitted.\n3. Acute or chronic uncontrolled pancreatitis or Child-Pugh Class B or C liver disease.\n4. A history of life-threatening hypersensitivity to monoclonal antibodies or recombinant proteins",{"count":256,"type":23},990,[175],"The objective of SAFIR-IMPACT BTC is to see whether, combining or replacing the standard adjuvant chemotherapy with a targeted therapy matched to the person's cancer, is better than the standard treatment alone in delaying or preventing the return of the cancer.\n\nThree different targeted therapies will be evaluated, each of which recognises a different type of abnormality in cancer cells:\n\n* Ivosidenib - a drug which acts on a specific abnormality in a protein called IDH1.\n* Futibatinib - a drug which acts on abnormalities in a protein called FGFR2\n* Zanidatamab - a drug which acts on cancers that produce more than the usual quantity of a protein called HER2.\n\nThe trial is composed of two phases:\n\n(i) An initial screening phase to identify a suitable patient population, during which a sample of the patient's tumour will be tested to see if it has one of the target abnormalities being studied (ii) a randomised comparative phase (for selected patients only) which consists of comparing two treatment options: some patients will receive the targeted therapy specific to the abnormality identified in their tumour, while others will receive the standard treatment. Patients will be assigned to one treatment or the other by a random draw: they will have a 2 in 3 chance of receiving the targeted therapy.\n\nRandomised participants will:\n\n* Take their assigned treatment for 6 months\n* Visit the clinic once every 3 weeks for checkups and tests\n* Keep a diary of their symptoms and the treatment they take at home Follow-up information will be collected for all participants until the end of the trial.",[260],"Biliary Tract Cancer (BTC)",[262,263,264,265,266],"Adjuvant","Targeted therapy","ESCAT","Personalised medicine","Cholangiocarcinoma","2026-07-29",{"date":269,"type":37},"2026-08-04",{"date":271,"type":23},"2027-01-02",{"date":273,"type":23},"2033-07-02",{"name":43,"class":44},{"id":276,"slug":277,"hasResults":12,"nctId":278,"briefTitle":279,"officialTitle":280,"acronym":281,"eligibilityCriteria":282,"healthyVolunteers":12,"sex":18,"minAge":283,"maxAge":4,"enrollmentInfo":284,"targetDuration":4,"studyType":24,"phases":286,"briefSummary":287,"conditions":288,"keywords":290,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":300,"lastUpdatePostDateStruct":301,"startDateStruct":303,"completionDateStruct":304,"leadSponsor":306,"locationsCount":4},"100602076","phase-3-study-evaluating-two-treatment-strategies-for-rectal-cancer-in-patients-75-years-old-100602076","NCT07118800","Study Evaluating Two Treatment Strategies for Rectal Cancer in Patients ≥75 Years Old","Randomized Phase III Study Evaluating Two Treatment Strategies for Locally Advanced Rectal Cancer in Patients ≥75 Years Old","NACRE-2","Inclusion Criteria:\n\n1. Histologically confirmed diagnosis of adenocarcinoma of the rectum\n2. Age ≥75 years\n3. WHO performance status 0-1\n4. cT3a-b with maximum diameter \\> 5 cm, T3c-d or cT4 tumor on pretreatment pelvic MRI\n5. General condition considered suitable for radical pelvic surgery and a systemic therapy with FOLFOX,\n6. Distal part of the tumor ≤10 cm from the anal margin, the measurement done by pelvic MRI\n7. Oncogeriatrician approval\n8. Adequate biological function defined by:\n\n   1. Neutrophils ≥ 1500\u002Fmm3\n   2. Platelets ≥ 100 000\u002Fmm3\n   3. Hemoglobin ≥ 10g\u002FdL\n   4. Total bilirubin ≤ 1,5 x ULN\n   5. Alkaline phosphatases ≤ 1,5 x ULN\n   6. Creatinine clearance \\>50mL\u002Fmn (MDRD)\n9. Men must agree to use adequate contraception methods for the duration of study treatment and for within 6 months after completing treatment\n10. Patients must be affiliated to a Social Security System (or equivalent).\n11. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent\n12. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.\n\nExclusion Criteria:\n\n1. Metastatic disease\n2. Other cancer within 3 years prior to rectal cancer diagnosis (except for in situ cancer and basal cell carcinoma of the skin)\n3. Non resectable cancer, including extension to prostate or extension to perineal muscles\n4. History of pelvic irradiation\n5. Contraindication to FOLFOX 4s chemotherapy and\u002For radiotherapy and\u002For TME surgery\n6. Contraindication to MRI\n7. Microsatellite instability (MSI) and\u002For mismatch repair deficiency (dMMR)\n8. Complete or partial Dihydropyrimidine Deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng\u002FmL)\n9. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before start of treatment\n10. Any other serious concomitant disease or disorder that may interfere with the patient's participation in the study and safety during the study (e.g., severe liver, heart, kidney, lung, metabolic, or psychiatric disorders).\n11. Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization\n12. Any psychiatric disorder precluding understanding of information of trial related topics and giving informed consent\n13. No prior chemotherapy or surgery for rectal cancer\n14. Any serious underlying medical condition (as judged by the investigator) that could impair the ability of the patient to participate in the trial\n15. Persons deprived of their liberty or under protective custody or guardianship.\n16. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.","75 Years",{"count":285,"type":23},160,[175],"The primary objective of the NACRE-2 trial is to assess whether the addition of chemotherapy after short-course radiotherapy is more effective than short-course radiotherapy alone in elderly patients with locally advanced rectal cancer. Secondary objectives will assess the efficacy and safety profile of the combination, as well as its effect on patients' quality of life.\n\nPatients will be separated into two groups to receive their assigned treatment:\n\n* Group 1: Short-duration radiotherapy according to standard practice lasting one week, followed by chemotherapy with FOLFOX4s consisting of oxaliplatin (85 mg\u002Fm²), folinic acid (400 mg\u002Fm²) and 5-Fluoro-Uracil (400 mg\u002Fm² administered in hospital, followed by 2400 mg\u002Fm² administered over 46 hours at home) every two weeks for 3 months\n* Group 2: Short-duration radiotherapy according to standard practice, lasting one week To receive treatment, patients must come to the hospital where, at each visit, the medical team will carry out medical examinations, prior to administering treatment, to assess the patient's general state of health and tolerance to treatment.\n\nA radiological assessment of the disease will be carried out 11 weeks after the end of radiotherapy. Patients whose tumors have not shrunk will undergo surgery to remove them and enter the follow-up phase. Patients whose tumors have shrunk will not undergo surgery, and will enter a surveillance phase. At 21 weeks, patients whose tumors are still present will undergo surgery and enter the follow-up phase. Patients whose tumors have disappeared will remain in a surveillance phase.\n\nDuring the surveillance or follow-up phases, patients will be monitored in hospital every 3 months (if no progression is observed). In the case of surgery, patients will be monitored every 6 months. The maximum duration of treatment is 3 years.",[289],"Locally Advanced Rectal Adenocarcinoma",[291,292,293,294,295,296,297,298,299],"Locally advanced","Rectum","Resectable","Adenocarcinoma","FOLFOX","Total neoadjuvant treatment","watch and wait","Non operative management","Short Course Radiotherapy","2026-07-23",{"date":302,"type":37},"2026-07-24",{"date":302,"type":23},{"date":305,"type":23},"2032-01-15",{"name":43,"class":44},{"id":308,"slug":309,"hasResults":12,"nctId":310,"briefTitle":311,"officialTitle":312,"acronym":313,"eligibilityCriteria":314,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":315,"targetDuration":4,"studyType":24,"phases":317,"briefSummary":318,"conditions":319,"keywords":321,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":300,"lastUpdatePostDateStruct":326,"startDateStruct":327,"completionDateStruct":329,"leadSponsor":331,"locationsCount":332},"100522112","phase-2-pembrolizumab-and-chemotherapy-treatment-or-no-treatment-guided-by-the-level-of-tils-in-resected-early-stage-tnbc-100522112","NCT06078384","Pembrolizumab and Chemotherapy Treatment or no Treatment Guided by the Level of TILs in Resected Early-stage TNBC","Adjuvant Pembrolizumab and Chemotherapy or Surveillance in Early Triple Negative breAst Cancer With High Stromal Tumor-infiltrating Lymphocytes (TILs) Score","ETNA","Inclusion Criteria:\n\n1. Understand, sign, and date the written informed consent form prior to any protocol- specific procedures performed,\n2. Men and women aged ≥ 18 years,\n3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1,\n4. Histologically confirmed and radically removed pT1b\u002Fc N0M0 TNBC as defined according to AJCC TNM stage-8th version,\n\n   * Histologically documented TNBC (negative HER2, ER, and PgR status). HER2 negativity is defined by local laboratory assessment using in situ hybridization and immunohistochemistry assays as per ASCO\u002FCAP criteria and ER\u002FPgR negativity is defined by local laboratory assessment \\\u003C 10% using immunohistochemistry assays,\n   * Bilateral and\u002For multifocal primary tumor is allowed and the tumor with the most advanced T stage should be used to asses for eligibility. If multifocal tumor, a pathologic confirmation of TNBC is required for each focus,\n5. Adequately excised breast cancer: subjects must have undergone either breast- conserving surgery or mastectomy\u002Fnipple- or skin-sparing mastectomy.\n\n   * For subjects who undergo breast-conserving surgery, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist. Reresections to ensure no ink on tumor margins are allowed. Subjects with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection.\n   * For subjects who undergo mastectomy\u002Fnipple- or skin-sparing mastectomy, margins must be free of gross residual tumor. It is recommended that subjects should have a negative microscopic margin in accordance with local pathology protocol,\n6. Have had sentinel lymph node biopsy (SLNB) and\u002For axillary lymph node dissection (ALND) for evaluation of pathologic nodal status.\n\n   Axillary nodal dissection(s) should yield a total of at least six nodes (including the axillary lymph nodes resected at the SLNB plus the lymph nodes collected at the axillary nodal dissection),\n7. At least 4 weeks but no more than 12 weeks between definitive breast surgery (or the last surgery with curative intent if additional resection is required for breast cancer) and treatment initiation for cohort 1 and no more than 12 weeks for cohort 2,\n8. Centrally assessed TILs score from surgical formalin-fixed paraffin embedded (FFPE) tumor sample, using an H\\&E stained diagnostic digital slide, according to the most recent International TILs Working Group guidelines,\n\n   * Cohort 1 will include patients aged \\> 40 years with 30% ≤ sTILs \\\u003C 50% and those aged\n\n     * 40 years with 30% ≤ sTILs \\\u003C 75%\n   * Cohort 2 will include patients aged \\> 40 years with sTILs ≥ 50% and those aged ≤ 40 years with sTILs ≥ 75%\n9. Women of childbearing potential have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication for cohort 1 and within 7 days of inclusion for cohort 2,\n10. Women of childbearing potential must agree to use protocol-specified method(s) of contraception for 3 years after patient inclusion. Men subjects who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception during trial treatments and for at least 6 months after the last dose of trial treatments.\n\n    Females of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \\> 1 year,\n11. Patients affiliated to the social security system (or equivalent)- France only,\n12. Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.\n\n    Additional inclusion criteria for subjects of cohort 1:\n13. Left ventricular ejection fraction (LVEF) of ≥ 50% as assessed by echocardiogram or cardiac scintigraphy,\n14. Demonstrate adequate organ function within 7 days of inclusion\n\n    * Absolute Neutrophil Count (ANC) ≥ 1,500 \u002FµL\n    * Platelets ≥ 100,000 \u002FµL\n    * Hemoglobin ≥ 9 g\u002FdL\n    * Creatinine clearance ≥ 30 mL\u002Fmin for subject with creatinine levels \\> 1.5 x institutional upper limit of normal (ULN)\n    * Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels \\> 1.5 ULN\n    * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN\n    * Albumin ≥ 3.0 g\u002FdL\n    * Lactate dehydrogenase (LDH) \\\u003C 2.5 X ULN\n    * International normalized ratio\u002Fpartial thromboplastin time (INR\u002FPTT) ≤ 1.5 x ULN (unless subject is receiving anticoagulant therapy as long as prothrombin time (PT) or PTT is within therapeutic range of intended use of anticoagulants)\n    * Thyroid stimulating hormone (TSH), free T4 (FT4), and free T3 (FT3) within normal ranges\n    * Cortisol at 8 AM within normal ranges\n    * Lipase and amylase \\\u003C 3 ULN\n    * Fasting plasma glucose ≤ 120 mg\u002Fdl or 6.7 mmol\u002FL\n    * Troponin within normal range\n\nExclusion Criteria:\n\n1. History of invasive malignancy ≤ 3 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer,\n2. Having received prior chemotherapy or targeted therapy within the past 12 months,\n3. Has a prior history of DCIS and\u002For LCIS that was treated with any form of systemic, hormonal therapy, or radiotherapy to the ipsilateral breast; subjects who had their DCIS\u002FLCIS treated only with surgery and\u002For contralateral DCIS treated with radiotherapy are allowed to enter the study,\n4. Having received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agents or with an agent directed to another co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137),\n5. Treatment with systemic immunostimulatory agents (including, but not limited to, interferons, interleukin-2) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to inclusion,\n6. 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 medications (including prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \\[anti-TNF\\] alpha agents) within 7 days prior to inclusion:\n\n   * Subjects who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study\n   * The use of inhaled corticosteroids and mineralocorticoids is allowed,\n7. 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) is not considered a form of systemic treatment; subjects with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible if:\n\n   * Rash must covers \\\u003C10% of body surface area.\n   * Disease is well controlled at baseline and requires only low-potency topical Corticosteroids and no acute exacerbations requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or oral corticosteroids occurred within the previous 12 months,\n8. Has a known history of Human Immunodeficiency Virus (HIV),\n9. Prior allogeneic stem cell or solid organ transplant,\n10. Has a known history of active Bacillus Tuberculosis,\n11. Patients with any other disease or illness which requires hospitalisation or is incompatible with the trial treatment are not eligible,\n12. Pregnant women or breastfeeding or expecting to conceive within the projected duration of the study, from the inclusion visit until the end of the 3 years follow up. Men subjects who engage in heterosexual intercourse and refuse to use protocol-specified method(s) of contraception during trial treatments and for at least 6 months after the last dose of trial treatments,\n13. Patients unable to comply with trial obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the trial,\n14. Person deprived of their liberty or under protective custody or guardianship,\n15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n\n    Additional non-inclusion criteria for subjects of cohort 1:\n16. Has cardiac dysfunction as defined by any of the following prior to inclusion:\n\n    * History of NCI-CTCAE v5.0 Grade \\> 3 symptomatic congestive heart failure or New York Heart Association (NYHA) criteria Class II,\n    * Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease,\n    * Significant symptoms (≥ Grade 2) relating to left ventricular dysfunction or cardiac ischemia,\n17. Has a known hypersensitivity (≥ Grade 3) to the components of the study therapy or its analogs,\n18. Has received a live vaccine or live-attenuated vaccine within 30 days of the first dose of study treatment,\n19. Concurrent active Hepatitis B virus (HBV; defined as HBsAg positive and\u002For detectable HBV DNA) and Hepatitis C virus (HCV; defined as anti-HCV Ab positive and detectable HCV RNA) infection,\n20. Severe infections within 4 weeks prior to initiation of study treatment, including, hospitalization for complications of infection, bacteremia, or severe pneumonia,\n21. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment; subjects receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection) are eligible,\n22. Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during study treatment,\n23. Has a history of (non-infectious) pneumonitis\u002Finterstitial lung disease that required steroids or has a current pneumonitis\u002Finterstitial lung disease,\n24. Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 4 weeks of the first dose of treatment in this current trial.",{"count":316,"type":23},354,[58],"Triple-negative breast cancer (TNBC) is a group of tumors that occurs mainly in young, premenopausal women and accounts for 10-20% of breast cancers. Over the past decade, the incidence of women diagnosed with early-stage TNBC has significantly increased due to the widespread use of screening mammography. Treatment of patients with localized TNBC mainly involves surgery and (neo)adjuvant chemotherapy with or without radiotherapy. However, the benefit of chemotherapy may be controversial in patients with early-stage TNBC defined by small size and absence of lymph node involvement, and with significant tumor lymphocyte infiltration.\n\nThe ETNA study is a phase II trial designed to evaluate a chemotherapy de-escalation strategy in patients with TNBC T1b\u002Fc N0M0 and stromal TILs (sTILs) ≥ 30%. ETNA comprises two cohorts defined according to the level of TILs and the age of patients. Patients aged \\> 40 years with 30% ≤ sTILs \\\u003C 50% and those aged ≤ 40 years with 30% ≤ sTILs \\\u003C 75% will be included in the cohort 1 and will receive adjuvant pembrolizumab 200 mg every three weeks for 9 cycles and Paclitaxel 80 mg\u002Fm² weekly for 12 cycles. Patients aged \\> 40 years with sTILs ≥ 50% and those aged ≤ 40 years with sTILs ≥ 75% will be included in cohort 2 and will not receive adjuvant treatment, they will undergo standard surveillance every six months.",[320],"Triple-negative Breast Cancer",[322,323,324,325],"Breast cancer","De-escalation","Immunotherapy","Chemotherapy",{"date":302,"type":37},{"date":328,"type":37},"2024-12-27",{"date":330,"type":23},"2032-01-01",{"name":43,"class":44},44,{"id":334,"slug":335,"hasResults":12,"nctId":336,"briefTitle":337,"officialTitle":338,"acronym":339,"eligibilityCriteria":340,"healthyVolunteers":341,"sex":170,"minAge":342,"maxAge":343,"enrollmentInfo":344,"targetDuration":4,"studyType":24,"phases":346,"briefSummary":347,"conditions":348,"keywords":350,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":352,"lastUpdatePostDateStruct":353,"startDateStruct":354,"completionDateStruct":356,"leadSponsor":357,"locationsCount":358},"100602175","evaluation-of-an-online-intervention-to-educate-women-at-high-risk-of-breast-cancer-on-how-to-help-reduce-their-risk-100602175","NCT07120087","Evaluation of an Online Intervention to Educate Women at High Risk of Breast Cancer on How to Help Reduce Their Risk.","Evaluation of a Virtual Risk-reduction Intervention Among Women at Higher Than Average Risk of Breast Cancer in the European MyPeBS Screening Trial","MyPREV","Inclusion Criteria:\n\n1. Female (whether born female or not)\n2. Women aged 40 to 74 years (inclusive)\n3. Women who have participated in, or are participating in the MyPeBS study and who fulfilled all the inclusion and non-inclusion criteria for the MyPeBS study.\n4. Women able to express their non-opposition to participate in the intervention\n5. Women who were assessed as being at high (≥≥1.67% - 5.9%) or very high (≥≥6%) risk of invasive breast cancer at 5 years in the MyPeBS study\n\nExclusion Criteria:\n\n1\\. Women who developed a breast cancer during their follow-up in the MyPeBS study",true,"40 Years","74 Years",{"count":345,"type":23},1508,[26],"Breast cancer remains the most common cancer among women and a major cause of death despite advances in screening and treatment. Current screening programs are not personalized and are experiencing declining participation. A promising strategy for breast cancer control would be to implement risk-based prevention and early screening, targeting individuals at high risk of developing breast cancer, in order to improve chances of cure and reduce the need for more intensive treatments. The MyPeBS study was designed to assess whether personalized breast cancer screening (based on an individual's risk of developing breast cancer) is as effective as, or more effective than, current standard screening.\n\nLifestyle interventions involving changes in diet or physical activity, for example, have been shown to be effective in reducing the risk of developing breast cancer, whether low or high. The MyPeBS study evaluates personalized screening but offers limited information on breast cancer prevention. MyPREV is a project that aims to assess the feasibility and impact of a personalized online program on breast cancer risk reduction measures. This program is offered to women at high risk of developing breast cancer as part of the European MyPeBS screening study.\n\nThe main objective is to evaluate adherence to a personalized, online breast cancer prevention program focused on lifestyle and its acceptance among women at high or very high risk of developing cancer who participated in the MyPeBS study.",[349],"Breast Cancer",[351],"Prevent and treat - breast cancer screening","2026-07-22",{"date":300,"type":37},{"date":355,"type":37},"2026-02-19",{"date":134,"type":23},{"name":43,"class":44},3,{"id":360,"slug":361,"hasResults":12,"nctId":362,"briefTitle":363,"officialTitle":364,"acronym":365,"eligibilityCriteria":366,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":367,"targetDuration":4,"studyType":24,"phases":369,"briefSummary":370,"conditions":371,"keywords":4,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":352,"lastUpdatePostDateStruct":374,"startDateStruct":375,"completionDateStruct":377,"leadSponsor":379,"locationsCount":104},"100562712","phase-3-personalizing-the-use-of-pembrolizumab-for-patients-who-have-a-strong-response-in-early-triple-negative-breast-cancer-100562712","NCT06606730","Personalizing the Use of Pembrolizumab for Patients Who Have a Strong Response in Early Triple Negative Breast Cancer","OPTimizing Adjuvant Prescription of PEMBROlizumab in Patients With Early-stage Triple-negative Breast Cancer Achieving Pathologic Complete Response After Standard Neoadjuvant Chemotherapy and Pembrolizumab","OPT-PEMBRO","Inclusion Criteria:\n\n1. Patient must have signed a written informed consent prior to any trial-related procedures. When the patient is physically unable to give his written consent, a trusted person of his choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent;\n2. Age ≥ 18 years;\n3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;\n4. Histologically documented stage II-III breast cancer according to the primary tumour-regional lymph node anatomic staging criteria of the American Joint Committee on Cancer (AJCC), 8th edition as determined by the investigator during radiologic assessment, clinical assessment or both;\n5. Estrogen receptor (ER) and Progesterone receptor (PR) ≤10%; HER2-negative as per ASCO\u002FCAP guidelines Note: In case of bilateral breast cancer, participation in the study is permitted as long as both tumours are triple negative;\n6. Patients previously treated with neoadjuvant chemotherapy in combination with pembrolizumab for a minimum of 6 cycles (All systemic chemotherapy must have been completed preoperatively);\n7. Absence of residual invasive disease in the breast or lymph nodes after the completion of neoadjuvant therapy (Residual ductal carcinoma in situ \\[DCIS\\] is allowed);\n8. Have had an adequately excised breast cancer (surgical removal of all clinically evident disease in the breast and lymph nodes) :\n\n   1. Breast surgery: patients must have undergone either breast-conserving surgery or total mastectomy with histologically negative margins for invasive tumour and DCIS. Patients with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection.\n   2. Lymph node surgery: patients must have had sentinel lymph node biopsy (SLNB) and\u002For axillary lymph node dissection (ALND) to evaluate the pathologic nodal status;\n9. Patients that have received adequate locoregional radiation therapy or with planned adequate locoregional radiation therapy;\n10. Adequate organ and bone marrow functions. All screening lab tests should be performed within 28 days before randomisation;\n\n    1. Absolute Neutrophil Count (ANC) ≥ 1,000 \u002FµL\n    2. Platelets ≥ 100,000 \u002FµL\n    3. Hemoglobin ≥ 9 g\u002FdL\n    4. Creatinine clearance ≥ 30 mL\u002Fmin for subject with creatinine levels \\> 1.5 x institutional upper limit of normal (ULN)\n    5. Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels \\> 1.5 ULN (Patients with Gilbert's disease with a total bilirubin ≤ 2.5 x ULN and direct bilirubin within normal limits are permitted)\n    6. Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 2.5 x ULN\n11. Randomisation must take place no more than 12 weeks after breast surgery. Adjuvant radiotherapy is authorized. If given, as per investigator discretion it can be given concurrently with pembrolizumab;\n12. Patients must not be pregnant or nursing (for women of childbearing potential only, a negative serum pregnancy test must be obtained within 7 days of Cycle 1 Day 1);\n13. Women of childbearing potential and male patients must agree to use 1 effective form of contraception and up to 4 months after the last dose of study drugs;\n14. Patients should be able and willing to comply with study visits and procedures as per protocol;\n15. Patients must be affiliated to a Social Security System (or equivalent).\n\nExclusion Criteria:\n\n1. Radiological or clinical evidence of metastatic disease (stage IV) documented by imaging or clinical examination;\n2. Evidence of recurrent disease following preoperative therapy and surgery;\n3. Any prior history of (ipsi- or contralateral) invasive breast cancer;\n4. Patients with a prior or concurrent malignancy (other than invasive breast cancer) whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of the investigational regimen;\n5. Patients for whom pembrolizumab has been permanently discontinued during the neoadjuvant phase of treatment due to pembrolizumab-related AE;\n6. History of intolerance, including Grade 3 or 4 infusion reaction or hypersensitivity to pembrolizumab or murine proteins or any component of the product;\n7. Medical conditions that require chronic systemic steroids (\\> 10 mg prednisone or equivalent) or any other form of immunosuppressive medication in the past 2 years. Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment;\n8. Known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitis;\n9. HIV-infected patients on effective anti-retroviral therapy with detectable viral load within 6 months prior to enrollment;\n10. 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 2B or better;\n11. Patients unwilling or unable to comply with the medical follow-up required by the trial due to geographic, familial, social, or psychological reasons;\n12. Persons deprived of their liberty or under protective custody or guardianship;\n13. Participation in another therapeutic trial within the 30 days prior to randomisation.",{"count":368,"type":23},2454,[175],"OPT-PEMBRO trial is a pragmatic, multicentre, international, prospective, non-inferiority, two-arms, randomised (1:1), open-label, Phase III clinical study.\n\nThe main goal of this research is to determine if patients with triple-negative breast cancer, who experience a complete response after neoadjuvant treatment, have the same chance of avoiding cancer recurrence whether they stop pembrolizumab or continue taking it for an additional 6 months.\n\nThis research will also take into account patients tolerance to treatment and quality of life.",[372,373],"Breast Cancers","Triple Negative Breast Cancer (TNBC)",{"date":300,"type":37},{"date":376,"type":37},"2025-07-23",{"date":378,"type":23},"2039-06-01",{"name":43,"class":44},{"id":381,"slug":382,"hasResults":12,"nctId":383,"briefTitle":384,"officialTitle":385,"acronym":386,"eligibilityCriteria":387,"healthyVolunteers":12,"sex":18,"minAge":388,"maxAge":4,"enrollmentInfo":389,"targetDuration":4,"studyType":24,"phases":391,"briefSummary":392,"conditions":393,"keywords":396,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":402,"lastUpdatePostDateStruct":403,"startDateStruct":405,"completionDateStruct":407,"leadSponsor":409,"locationsCount":4},"100626087","phase-2-immunotherapy-master-trial-for-advanced-cancers-100626087","NCT07431073","Immunotherapy Master Trial for Advanced Cancers","Adaptive Master Trial for Advanced Cancers With Rapid Evaluation of Molecular & Immune Status for Stratified Immunotherapies in Oncology","METAREM","Inclusion Criteria:\n\n1. Age ≥12 years with at least 40kg body weight or otherwise as per specified in sub-protocol.\n2. Prior to the inclusion in the METAREM master protocol, patients must have signed a written informed consent to baseline PORTRAIT evaluation and on-treatment PORTRAIT evaluation.\n\n   Note:\n   1. When the patient is physically unable to give his\u002Fher written consent, an impartial witness a trusted person of his\u002Fher choice, independent from the investigators or the sponsor, can confirm in signing the patient's consent.\n   2. For patients aged between \\> 12 and \\\u003C 18, specific consent from legal tutors should be obtained on top of the minor consent and prior procedures.\n3. Patients with advanced cancer, as defined as unresectable locally advanced malignancies or metastatic cancers (including leukemias and lymphomas).\n4. Having measurable disease (i.e one measurable lesion according to RECIST v1.1 for solid tumors or one consensus method of blast quantification \u002F minimal residual disease assessment for leukemias).\n5. Eastern cooperative oncology group (ECOG) performance status between 0 and 2.\n6. Patients amenable to undergo a blood draw procedure and a tumor biopsy procedure. For patients with more than 10% malignant cells in their bone marrow or blood, a bone marrow aspirate or blood draw could replace the tumor biopsy.\n7. Adequate organ function as defined by the following criteria:\n\n   * Total bilirubin ≤1.5 ULN, or ≤3.0 ULN in participants with Hepato-Cellular Carcinoma (HCC) or known Gilbert's syndrome if the increase is predominantly due to unconjugated bilirubin.\n   * ALT ≤ 3 x ULN; if liver metastases ALT ≤ 5 x ULN\n   * Absolute Neutrophils count (ANC) ≥ 1000 cells\u002Fmm³ in the absence of G-CSF or GM-CSF within ≤2 weeks before the first dose of study treatment.\n   * Platelets ≥100 000 cells\u002Fmm³\n   * Hemoglobin ≥ 9.0 g\u002FdL\n   * Albumin ≥ 30 g\u002FL\n   * Calculated creatinine clearance ≥50 mL\u002Fmin\u002F1.73 m2\n8. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment.\n9. Both sexually active WOCBP and males (and their WOCBP partners) patients must agree to use two methods of effective contraception, one of them being a physical barrier method, or to abstain from sexual activity during the study and for the period indicated in specific sub-protocol after the last study drug administration.\n10. Patient affiliated to the French social security regimen.\n11. Patients with mental and legal ability to fully consent for undergoing the exploratory procedures (blood draws and biopsies) prior (at baseline PORTRAIT) and upon treatment and (on-treatment PORTRAIT).\n12. Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.\n\nExclusion Criteria:\n\n1. Any life-threatening allergy to one of the experimental products tested in the sub-protocol where the patient is eligible. In case of allergy to contrast media, patient monitoring should be performed with alternate methods (both CT-scan or MRI).\n2. History of life threatening autoimmune\u002Fimmune mediated inflammatory disease, including but not limited to severe colitis, pneumonitis, Guillain-Barré syndrome, anti-phospholipid syndromes and myocarditis. Patients with a history of auto-immune endocrinopathy (hypo\u002Fhyper thyroiditis, type 1 diabetes mellitus, …) and who are stable on hormone replacement therapy are eligible for the study. Patients with a history of vitiligo, alopecia areata, cutaneous psoriasis and grade 1-2 Sjogren syndrome are eligible.\n3. Treatment with systemic long-term immunosuppressive medications unless otherwise specified in the specific therapeutic sub-protocols. Those immunosuppressive drugs must have been stopped at least 4 weeks prior to enrollment. Hormone replacement therapy with physiological doses of hydrocortisone is acceptable.\n4. Chemotherapy, hormonotherapy, radiotherapy or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks or 5 half-life times (whatever the shortest) prior to treatment with the trial drugs.\n5. Administration of a live, attenuated vaccine within 4 weeks before registration.\n6. Radiotherapy to the chosen RECIST target lesion(s) (unless a progression after radiotherapy has been documented).\n7. Persistence of a clinically relevant treatment-related toxicity from previous chemotherapy, targeted therapy and\u002For radiotherapy which could hamper the safety or efficacy assessment of the therapy tested (for previous disease).\n8. Patients with symptomatic brain metastases or leptomeningeal disease are excluded unless otherwise specified by a specific therapeutic sub-protocol. Clinically asymptomatic brain metastases and clinically asymptomatic leptomeningeal disease are allowed (treatment with steroids prior to initiation of the trial is not allowed).\n9. Patients with evolving tumors next to cavitary or major blood vessels at high risk of massive bleeding and\u002For perforation.\n10. History of clinically significant hemoptysis within the past 3 months.\n11. Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial.\n12. Major injuries and\u002For surgery within the past 4 weeks prior to start of study treatment with incomplete wound healing and\u002For planned major surgery during the on-treatment study period.\n13. History of clinically significant hemorrhagic or thromboembolic event in the past 3 months.\n14. History of significant cardiovascular diseases (i.e., supraventricular tachycardia, uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure \\> NYHA II, serious cardiac arrhythmia, pericardial effusion).\n15. Ongoing uncontrolled endocrinopathy. Ancient endocrinopathy currently stable with substitutive therapy should not be excluded from the trial.\n16. Other malignancies within the past 5 years other than superficial malignancies (e.g localized squamous or basal cell skin cancer) or carcinoma in situ (e.g cervix, breast, prostate, bladder) which have undergone curative therapies. A history of more than 3 years without subsequent relapse of local prostate cancer treated by surgery and without PSA elevation since surgery, or local breast carcinoma treated by surgery without relapse or resected non-muscle invasive bladder cancers are eligible.\n17. Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy. A wash out of more than 3 weeks is required after last systemic antibiotics to allow reconstitution of the microbiome. Patients infected by HIV but having efficient anti-retroviral therapy and CD4+ T-cell counts \\>500\u002Fmm³ are eligible. Patients with a history of HBV or HCV that are cured and have eligible liver function criteria are also eligible.\n18. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug in case an oral drug is tested in the sub-protocol for which the patient is screened.\n19. Pregnancy or breast feeding.\n20. Intake of Ganoderma Lucidum mushroom (also called \"Reishi\") and\u002For herbal remedies and\u002For traditional medicines within the past weeks prior to start of study treatment or concomitantly with the trial because of their potential to increase treatment related adverse events.\n21. Any psychological, familial, sociological, geographical factors, lifestyle, behavior, clinical or biological parameters or elements in the past medical history of the patients that, according to the investigator, could preclude the ability of the trial to directly reach its objectives, or indirectly via treatment observance or study follow up. Patients with active alcoholism and\u002For drug abuse are excluded.\n22. Person deprived of their liberty or under protective custody or guardianship.","12 Years",{"count":390,"type":23},275,[58],"Over the past decade, cancer immunotherapy has profoundly transformed oncology by harnessing the patient's immune system to target tumors. These therapies have demonstrated the potential for durable responses and, in some cases, long-term remission or cure. However, despite these advances, only approximately 20-30% of patients derive significant clinical benefit from current immunotherapies. In parallel, investment in oncology drug development continues to grow, with global spending projected to reach $307 billion by 2026. Yet, the overall failure rate in oncology drug development remains extremely high, at around 95%, highlighting a critical gap between scientific innovation and clinical success.\n\nOne major contributor to these failures lies in traditional drug development and regulatory paradigms, which have historically relied on cancer histology as the primary framework for patient selection and treatment evaluation. This approach is based on the flawed assumption that tumors of the same histological type share similar biological behavior and therapeutic vulnerabilities, and that localized and advanced disease are biologically comparable. In reality, tumor biology-rather than histology-plays a decisive role in determining immunotherapy efficacy. Substantial heterogeneity exists within the same cancer type, leading to widely variable patient outcomes even among individuals receiving identical treatments.\n\nThe recent emergence of tumor-agnostic approvals for immunotherapies has reinforced the importance of shared biological features across cancer types. Approvals of anti-PD-1 therapies for microsatellite instability-high (MSI-H), mismatch repair-deficient (dMMR), or tumor mutational burden-high (TMB-H) cancers have demonstrated that biological characteristics can transcend tissue of origin. However, the predictive value of current companion diagnostic assays remains limited. Only 30-40% of biomarker-positive patients respond to treatment, underscoring the inadequacy of existing patient selection strategies.\n\nThese limitations are partly driven by the methodologies used in industry-sponsored clinical trials, which typically rely on tumor samples processed by contract research organizations (CROs). For logistical reasons, analyses are performed on formalin-fixed paraffin-embedded (FFPE) or frozen tissues using conventional techniques such as immunohistochemistry (IHC) and DNA\u002FRNA sequencing. While informative, these methods are often slow, complex, and insufficiently sensitive or specific to guide timely treatment decisions, particularly when results are required within the 3-4 week window following trial consent. Moreover, they offer limited insight into dynamic parameters such as target expression, saturation, and engagement during treatment.\n\nThere is therefore a pressing need for innovative oncology drug development strategies that prioritize biologically driven patient selection, support tumor-agnostic approaches, and enable truly personalized cancer therapy. Addressing this need requires technologies capable of rapid, comprehensive, and functional immune and tumor profiling.\n\nMETAREM is part of the broader REMISSION program, which aims to improve treatment stratification and generate early clinical evidence to support the development of novel therapies and patient selection strategies. METAREM is a master protocol designed to test innovative treatment approaches through dedicated sub-protocols in patients with unresectable locally advanced or metastatic cancers. All patients enrolled in METAREM undergo in-depth immuno-biological characterization at both tumor and blood levels using the PORTRAIT immunoprofiling platform.\n\nPORTRAIT analysis is performed on fresh whole blood and fresh tumor biopsies, enabling rapid, sensitive, and highly specific profiling of each patient's immune and tumor biology. This real-time approach overcomes the limitations of conventional tissue-based assays and allows for a comprehensive understanding of disease mechanisms at the individual level. By integrating these data, METAREM aims to stratify patients into the most appropriate therapeutic sub-protocols, thereby advancing personalized cancer treatment and supporting more efficient, biology-driven drug development.",[394,395],"Advanced \u002F Metastatic Solid Tumors","Advanced Malignancy",[397,398,324,399,400,401],"Advanced Cancers","Metastatic tumors","Personalized therapy","Tumor Biology","Tumor Microenvironment","2026-07-20",{"date":404,"type":37},"2026-07-21",{"date":406,"type":23},"2026-07",{"date":408,"type":23},"2034-01",{"name":43,"class":44},{"id":411,"slug":412,"hasResults":12,"nctId":413,"briefTitle":414,"officialTitle":415,"acronym":416,"eligibilityCriteria":417,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":418,"targetDuration":4,"studyType":24,"phases":419,"briefSummary":420,"conditions":421,"keywords":423,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":402,"lastUpdatePostDateStruct":431,"startDateStruct":432,"completionDateStruct":433,"leadSponsor":435,"locationsCount":436},"100620678","phase-2-immunotherapy-without-chemotherapy-for-advanced-lung-cancer-patients-with-high-pd-l1-levels-100620678","NCT07360743","Immunotherapy Without Chemotherapy for Advanced Lung Cancer Patients With High PD-L1 Levels","Anti-PD1 Monotherapy in 1L Advanced NSCLC Patients With PD-L1 TPS > 50% and PTI=0","META-1","Inclusion Criteria:\n\nIn addition to the inclusion criteria of the METAREM master protocol, following additional criteria must be respected during patient inclusion in META-1 trial:\n\n1. Patients with age ≥18 years\n2. Patients in first-line therapy for advanced metastatic NSCLC with PD-L1 Tumor Proportion Score (TPS) \\>50%, without EGFR\u002F ALK\u002F ROS1 mutations and irrespective of their histological subtype (squamous or non-squamous).\n3. Patients with a PTI score of zero in plasma on the baseline PORTRAIT report. Note: Patients with PTI score ≥ 1 who meet all other criteria will be followed up to 36 months or death according to standard of care.\n\nExclusion Criteria:\n\nIn addition to the Exclusion criteria of the METAREM master protocol, following additional criteria must be considered during patient exclusion from META-1 trial:\n\n1. Patients who have previously received an anti-PD(L)1 or anti-CTLA4 or anti-LAG-3 or anti-TIM3 immunotherapy.\n2. Patients with any Hypersensitivity to the active ingredient or to any of the excipients of Pembrolizumab or Cemiplimab.",{"count":390,"type":23},[58],"Anti-PD-1 monotherapy has demonstrated significant clinical efficacy in advanced or metastatic non-small cell lung cancer (NSCLC) with high PD-L1 expression (tumor proportion score \\[TPS\\] \\>50%), outperforming platinum-based chemotherapy in terms of objective response rate (ORR) and overall survival (OS). Pivotal randomized trials such as KEYNOTE-024 and EMPOWER-Lung 1 established the superiority of PD-1 blockade in this patient population, leading to regulatory approvals by both the FDA and EMA for first-line treatment. These studies confirmed that a subset of patients can achieve deep and durable responses with immunotherapy alone, highlighting the potential of immune checkpoint inhibition to provide long-term clinical benefit without the toxicities associated with cytotoxic chemotherapy.\n\nDespite these successes, accumulating clinical evidence has revealed a clinically significant risk of hyperprogressive disease (HPD) in a subset of patients treated with anti-PD-1 monotherapy. HPD is characterized by an unexpected and rapid acceleration of tumor growth following treatment initiation and is associated with early clinical deterioration and increased mortality. This phenomenon likely contributes to the early crossover of survival curves frequently observed when comparing immunotherapy alone with chemotherapy in first-line NSCLC trials. In contrast, such early survival crossover is not observed in trials comparing chemotherapy-immunotherapy combinations with chemotherapy alone, including CheckMate-227, CheckMate-9LA, KEYNOTE-189, and KEYNOTE-407. These results have led many thoracic oncologists to favor combined chemo-immunotherapy regimens as first-line treatment, as they reduce the risk of HPD and increase initial ORR.\n\nHowever, while chemotherapy combined with immunotherapy effectively mitigates the risk of hyperprogression and improves early response rates, it also appears to compromise the durability of antitumor immune responses. Clinical data indicate that the median duration of response with chemo-immunotherapy combinations is approximately 10-11 months, compared with more than 22 months for anti-PD-1 monotherapy alone. This difference is likely attributable to the cytotoxic effects of chemotherapy on immune effector cells, which may limit the persistence and depth of immune-mediated tumor control. Consequently, there remains a strong clinical need to identify patients who could safely and effectively benefit from anti-PD-1 monotherapy while avoiding unnecessary exposure to chemotherapy.\n\nMultiple early-phase translational studies have independently identified soluble plasma biomarkers associated with response or resistance to PD-1 blockade in advanced NSCLC. Building on this body of evidence, translational analyses conducted at Gustave Roussy Cancer Center have identified a composite signature of circulating soluble factors, including interleukin-6 (IL-6), interleukin-8 (IL-8), soluble CD14 (sCD14), soluble CD25 (sCD25), and growth differentiation factor-15 (GDF-15). Together, these biomarkers define a Pro-Tumoral Inflammation (PTI) signature that is strongly associated with primary resistance to anti-PD-1 monotherapy. Elevated PTI scores reflect a systemic inflammatory state that promotes tumor progression and immune dysfunction, and have been linked to poor clinical outcomes, including non-response and hyperprogressive disease.\n\nWithin the META-1 sub-protocol of the METAREM master protocol, the investigators propose to integrate these soluble biomarkers into a single PTI score generated through baseline PORTRAIT immunoprofiling. The primary objective of this approach is to prospectively validate the predictive value of the PTI score for anti-PD-1 monotherapy efficacy in advanced NSCLC. By enabling early identification of patients at high risk of resistance or hyperprogression, this strategy aims to refine patient stratification and guide first-line treatment selection. Ultimately, the use of the PTI score could allow clinicians to identify patients most likely to benefit from anti-PD-1 monotherapy, preserving the potential for durable responses while sparing others from ineffective treatment and optimizing the overall therapeutic strategy in advanced NSCLC.",[422],"Non Small Cell Lung Cancer (Squamous or Non Squamous)",[424,425,426,427,428,429,430],"anti-PD1 monotherapy","non-small cell lung cancer (NSCLC)","Tumor Proportion Score (TPS) >50%","without EGFR\u002F ALK\u002F ROS1 mutations","Pro-tumoral inflammatory score (PTI)","Advanced metastatic cancers","Personalized immunotherapy",{"date":404,"type":37},{"date":155,"type":23},{"date":434,"type":23},"2032-04",{"name":43,"class":44},4,{"id":438,"slug":439,"hasResults":12,"nctId":440,"briefTitle":441,"officialTitle":442,"acronym":443,"eligibilityCriteria":444,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":445,"targetDuration":4,"studyType":24,"phases":447,"briefSummary":448,"conditions":449,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":402,"lastUpdatePostDateStruct":455,"startDateStruct":456,"completionDateStruct":457,"leadSponsor":459,"locationsCount":460},"100611491","spect-ct-guided-elective-contralateral-neck-treatment-in-lateralized-oropharyngeal-cancer-100611491","NCT07241273","SPECT-CT Guided ELEctive Contralateral Neck Treatment in Lateralized Oropharyngeal Cancer","SPECT-CT Guided ELEctive Contralateral Neck Treatment in Lateralized Oropharyngeal Cancer: A Phase II Trial","SELECT-FR","Inclusion Criteria:\n\n1. Patients must have signed a written informed consent form prior to any trial specific procedures.\n2. Patients with histologically confirmed T1-T3 M0 lateralized OPC (tonsil, soft palate, pharyngeal wall or base of tongue) not involving or crossing midline. Nodal disease may include no node or single or multiple ipsilateral lymph nodes (largest should be equal or less than 6 cm in maximum diameter) without contralateral nodes involved. For HPV-positive patients, this includes N0-N1. For HPV-negative patients, this includes N0-N2b. Patients with radiologic extranodal extension without clinical signs of extranodal extension (skin invasion, deep nodal fixation, and\u002For clinical signs of cranial nerve or brachial plexus invasion) will be eligible for participation.\n3. HPV-positive or -negative (by p16 immunohistochemistry). Tumours will be classified as p16 at local sites based on greater than 70% strong diffuse nuclear or nuclear and cytoplasmic staining.\n4. Planned definitive bilateral neck radiotherapy with or without concurrent chemotherapy.\n5. Patients ≥ 18 years old.\n6. ECOG Performance Status 0-1.\n7. The following radiological investigations must have been done within 8 weeks before randomization:\n\n   * CT or MRI of the neck (with head imaging as indicated);\n   * PET-CT scan;\n   * Chest CT scan.\n8. Patients who receive a concomitant chemoradiotherapy (cCRT) should have adequate organ and bone marrow function including the following:\n\n   * Hematological function (absolute neutrophil count ≥ 1.5 x10⁹\u002FL, platelets ≥ 100 x10⁹\u002FL, hemoglobin ≥ 9 g\u002FdL) measured before cCRT.\n   * Renal function (creatinine clearance ≥ 50 mL\u002Fmin per Cockcroft and Gault formula) measured before cCRT.\n   * Hepatic function (total bilirubin \\\u003C 1.5 ULN, Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \\\u003C 2.5 ULN, Alkaline phosphatase \\\u003C 2.5 ULN) measured before cCRT.\n9. Women\u002Fmen of childbearing potential must have agreed to use a highly effective contraceptive method up to 90 days after completing radiotherapy.\n\n   Women of childbearing potential must have a negative pregnancy test before the beginning of the trial.\n10. Treating surgeon must confirm that the patient is a candidate to undergo injection procedure for lymphatic mapping in either the nuclear medicine, ambulatory clinic, or operating room setting.\n11. Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.\n12. Patients affiliated to (or beneficiary from) the French social security system.\n13. 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\nExclusion Criteria:\n\n1. Patients with T1-T2 cancers isolated to the tonsil fossa (i.e., without any soft palate, tongue base, posterior pharyngeal wall or posterior tonsil pillar involvement) with no involved lymph nodes or with a single ipsilateral node \\\u003C 3 cm without extranodal extension.\n2. Patients with tonsil or tongue base primary squamous cell carcinoma who have previously undergone diagnostic palatine or lingual tonsillectomy with either complete excision or with no clinically apparent residual disease are excluded. However, patients who have had previous deep biopsies or partial excisions with clinically evaluable disease are still eligible.\n3. Previous head and neck cancer or multiple synchronous primary head and neck cancers.\n4. Previous induction or neo-adjuvant chemotherapy.\n5. Previous radiation therapy to the head and neck or comprehensive neck dissection of at least 3 levels on either side (due to potential for disrupted lymphatic channels and drainage pathways). Patients who have had excisional biopsies of involved lymph nodes are, however, still eligible.\n6. Previous radiotracer allergy. Contraindication in patients with history of hypersensitivity to human albumin-containing products.\n7. Patients with severe, active co-morbidity including any of the following:\n\n   * Chronic Obstructive Pulmonary Disease or other pulmonary illness requiring hospitalization within 30 days of registration.\n   * Unstable angina and\u002For congestive heart failure requiring hospitalization within the 30 days of registration.\n   * Acute myocardial infarction within 30 days of study registration.\n   * Diseases precluding RT (e.g., scleroderma).\n8. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, as assessed by the investigator.\n9. Pregnant or breastfeeding women.\n10. Patient enrolled in another therapeutic trial within 30 days of registration.\n11. Persons deprived of their liberty or under protective custody or guardianship.",{"count":446,"type":23},128,[26],"Oropharyngeal cancer (OPC) is the most common type of head and neck cancer. The current standard treatment for this cancer is radiotherapy (RT) of the tumour and lymph nodes of both sides of the neck, combined with concurrent chemotherapy for advanced stages. Even though a small proportion of patients with this cancer have involvement of the lymph nodes of the neck on the opposite side of the tumour (contralateral involvement) or involvement of the lymph nodes on both sides of the neck (bilateral involvement), bilateral radiotherapy is performed due to the risk of contralateral microscopic involvement, which is invisible on imaging and clinical examination. Bilateral radiotherapy causes more adverse events, leading to a decrease in quality of life.\n\nLymphatic mapping using Single Photon Emission Computed Tomography-Computed Tomography (SPECT-CT) imaging is a technique that visualises the lymphatic drainage of the tumour and thus determines whether radiotherapy should be delivered unilaterally or bilaterally to the lymph nodes. This technique would therefore reduce adverse events and improve quality of life, while maintaining the efficacy of radiotherapy.\n\nThe goal of the clinical trial SELECT-FR is to investigate if the efficacy of a lymphatic drainage mapping with a SPECT-CT-guided approach is acceptable in terms of two-year Disease Free Survival (DFS) rate in patients with lateralized OPC.",[450,451,452,238,453,454],"Oropharyngeal Squamous Cell Carcinoma","Oropharyngeal Cancers","Oropharyngeal Carcinoma","Head and Neck Cancer","Head and Neck Cancers",{"date":404,"type":37},{"date":100,"type":23},{"date":458,"type":23},"2031-09",{"name":43,"class":44},12,{"id":462,"slug":463,"hasResults":12,"nctId":464,"briefTitle":465,"officialTitle":466,"acronym":467,"eligibilityCriteria":468,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":469,"targetDuration":4,"studyType":24,"phases":471,"briefSummary":472,"conditions":473,"keywords":476,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":402,"lastUpdatePostDateStruct":482,"startDateStruct":483,"completionDateStruct":485,"leadSponsor":487,"locationsCount":218},"100610671","phase-2-neo-adjuvant-immunotherapy-in-patients-with-localized-melanoma-100610671","NCT07230613","Neo-adjuvant Immunotherapy in Patients With Localized Melanoma","Neo-adjuvant Intratumoral Anti-CTLA4 + Anti-PD1 in Patients With Localized Melanoma","NEOREM-NEO-1","In addition to NEOREM Master Protocol inclusion and exclusion criteria, the following inclusion and exclusion criteria must be verified before inclusion in the NEO-1 trial:\n\nInclusion Criteria:\n\n1. Patients ≥ 18 years old.\n2. Patients with resectable and measurable (according to RECIST v1.1 criteria) stage III cutaneous and mucosal melanoma.\n3. Patients who received anti-PD-1 and stopped treatment \\> 6 months prior to their inclusion in NEO-1 trial are eligible.\n4. Patients who received target therapy and stopped treatment \\> 3 months prior to their inclusion in NEO-1 trial are eligible.\n\nExclusion Criteria:\n\n1. Patients with clinically or radiologically detectable distant metastases.\n2. Patients with uveal melanoma.\n3. Patients with any hypersensitivity to the active ingredient or to any of the excipients of nivolumab and\u002F ipilimumab.\n4. Patients without pathological evaluable disease according to RECIST v1.1 criteria.",{"count":470,"type":23},50,[58],"The success of anti-PD-1 and anti-CTLA-4 therapies has initiated a paradigm shift in oncology, with drugs now targeting the immune system rather than cancer cells to stimulate the antitumor immune response. Intratumoral (IT) delivery of immunostimulating agents reduces the systemic toxicity associated with monoclonal antibodies (mAbs) targeting immune checkpoints. Notably, IT injections of immune checkpoint blockade (ICB) have been shown to induce immune-mediated tumor responses both at the injected site and at distant, non-injected tumor sites. While surgery has traditionally been the preferred treatment for stage III and IV melanoma patients, neoadjuvant therapy with anti-CTLA-4 and anti-PD-1 agents has shown promising efficacy.\n\nIn patients with localized melanoma, it is hypothesized that IT administration of ipilimumab (anti-CTLA-4 Ab) combined with nivolumab (anti-PD-1 Ab) will provide the most effective and safe treatment combination.\n\nThe NEO-1 study is a proof-of-concept clinical trial designed as a sub-protocol of NEOREM master protocol (NCT07262489) to validate the intratumoral immunotherapy approach, aiming to maximize the dose\u002Fefficacy ratio of combined ipilimumab and nivolumab treatment while minimizing systemic adverse events. This is an academic, open-label, multicentric, phase II clinical trial evaluating the efficacy and safety of intratumoral injections of ipilimumab and nivolumab combination as neoadjuvant treatment in localized stage III resectable cutaneous or mucosal melanoma patients.\n\nBaseline and on-treatment PORTRAIT profiling, as described in the NEOREM Master Protocol (NCT07262489), will be performed using fresh blood and tumor samples. This profiling will reveal the immune status of patients and support biomarker-driven preselection for future trials.",[474,475],"Cutaneous Melanoma, Stage III","Mucosal Melanoma",[477,478,479,480,481],"Neo-adjuvant Immunotherapy","Localized Cancers","Intra-tumoral treatment","Melanoma","Immune-checkpoint blockade",{"date":404,"type":37},{"date":484,"type":37},"2026-01-12",{"date":486,"type":23},"2033-12",{"name":43,"class":44},{"id":489,"slug":490,"hasResults":12,"nctId":491,"briefTitle":492,"officialTitle":493,"acronym":494,"eligibilityCriteria":495,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":496,"targetDuration":4,"studyType":24,"phases":498,"briefSummary":499,"conditions":500,"keywords":502,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":402,"lastUpdatePostDateStruct":505,"startDateStruct":506,"completionDateStruct":508,"leadSponsor":510,"locationsCount":511},"100550687","phase-2-decreasing-treatment-for-metastatic-her2-positive-breast-cancer-with-undectable-cancer-levels-in-blood-tests-100550687","NCT06450314","Decreasing Treatment for Metastatic HER2-Positive Breast Cancer With Undectable Cancer Levels in Blood Tests.","De-escalation of Medical Therapies in HER2-positive Metastatic Breast Cancer in Long-term Persistent Response and Minimal Residual Disease Undetectable in Circulating Tumor DNA","HEROES","Inclusion Criteria:\n\n1. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in signing the patient's consent;\n2. Men or women ≥18 years of age;\n3. Documented diagnosis of locally advanced inoperable or metastatic histologically-proven HER2-positive breast cancer (HER2-positive is defined as HER2 3+ immunohistochemical overexpression, or the presence of HER2 amplification, according to ASCO-CAP guidelines);\n4. Must have an adequate archival tumor tissue sample available for next-generation sequencing (NGS) analysis by central laboratory, in order to design the ctDNA test (based on most recent available tumor tissue sample, metastatic biopsy (bone tissue excluded) and primary tumor authorised);\n5. Patient with Eastern Cooperative Oncology Group - Performance Status (ECOG-PS) ≤1;\n6. Patient must have received continuous anti-HER2 targeted therapy (including Trastuzumab, Trastuzumab\u002FPertuzumab, Trastuzumab-Deruxtecan or T-DM1) treatment for at least 2 years in any line setting, for their locally advanced inoperable or metastatic HER2 + breast cancer (prior treatment interruption of 3 months maximum is allowed), with complete response or partial response at last radiological assessment;\n\n   Note: the number of patients who received anti-HER2 targeted therapy in second line setting or more will be capped to 50% of the overall population\n7. In case of bone disease only, complete metabolic response in 18-FDG pet-scanner is required;\n8. Patient with treated (surgery and\u002For radiation therapy) and controlled primary tumor;\n9. Patients with ER-positive disease may or may not have received concomitant endocrine therapy (which must be continued if present). Concomitant ovarian blockade using Luteinizing Hormone-Releasing Hormone (LHRH) agonists is authorised as well;\n10. Adequate cardiac, renal, haematological and hepatic functions according to guidelines hospital;\n11. Women of childbearing potential must have a negative serum or urine pregnancy test done within 28 days before inclusion;\n12. Non post-menopausal women and fertile men must agree to use adequate contraception methods during the study. Hormonal contraceptives such as birth control pills, patches, implants, or injections are not allowed in patients who are hormone receptor positive;\n13. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan and other study procedures including follow-up;\n14. Patients must be affiliated to a Social Security System (or equivalent).\n\nExclusion Criteria:\n\n1. Any breast cancer progression over the past 2 years or at study entry;\n2. Patient concurrently using other approved or investigational antineoplastic agents than trastuzumab, pertuzumab, Trastuzumab-Deruxtecan, TDM-1 +\u002F- endocrine therapy;\n3. Had an history of tumoral meningitis or clinically active central nervous system metastases, defined as untreated or symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms;\n\n   1. Subjects with curatively treated brain metastases (i.e., complete removal surgery or stereotactic radiotherapy) who are no longer symptomatic and do not require treatment with corticosteroids or anticonvulsants may be included in the study provided they have recovered from the acute toxicity of radiotherapy and there has been no progression of the brain metastases within the past 24 months.\n   2. Subjects with brain metastases only or treated with whole brain radiotherapy will be excluded of the study\n4. Major concurrent disease affecting cardiovascular system, liver, kidneys, haematopoietic system or else considered as clinically important by the investigator and that could be incompatible with patient's participation in this trial or would likely interfere with study procedures or results;\n5. History of any prior ipsi or contralateral breast cancer (except in case of DCIS) unless if both primary tumors were confirmed to be HER2-positive;\n6. Prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease and treatment for at least 3 years;\n7. Major surgery within 2 weeks prior to study entry;\n8. Pregnant women or women who are breast-feeding;\n9. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons;\n10. Participation in another clinical study whose procedures interfere with those of the study (within 28 days prior to patient enrolment and for the duration of the study);\n11. Persons deprived of their liberty or under protective custody or guardianship.",{"count":497,"type":23},170,[58],"Heroes is a multicentre, national, non-randomized, open-label, phase 2 study. The goal of this clinical trial is to evaluate the feasibility of therapeutic de-escalation in HER2-positive metastatic breast cancer with disease controlled after 2 years of maintenance treatment with anti-HER2 targeted therapy AND ctDNA negative testing.\n\nThe main question it aims to answer is :\n\n• Is it possible to identify patients for whom temporary or permanent discontinuation of treatment is possible without impacting prognosis?",[97,501],"HER2-positive Breast Cancer",[503,504],"de-escalation","ctDNA test",{"date":404,"type":37},{"date":507,"type":37},"2025-01-25",{"date":509,"type":23},"2029-12-15",{"name":43,"class":44},1,{"id":513,"slug":514,"hasResults":12,"nctId":515,"briefTitle":516,"officialTitle":517,"acronym":518,"eligibilityCriteria":519,"healthyVolunteers":12,"sex":170,"minAge":520,"maxAge":4,"enrollmentInfo":521,"targetDuration":4,"studyType":24,"phases":523,"briefSummary":524,"conditions":525,"keywords":4,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":402,"lastUpdatePostDateStruct":526,"startDateStruct":527,"completionDateStruct":529,"leadSponsor":531,"locationsCount":104},"100462127","phase-2-deescalation-of-endocrine-therapy-duration-in-women-with-hr-her2--breast-cancer-at-very-low-risk-100462127","NCT05297617","Deescalation of Endocrine Therapy Duration in Women With HR+ HER2- Breast Cancer at Very Low Risk","Single-arm Study to De-escalate Adjuvant Endocrine Therapy Duration in Women With HR+ HER2- Breast Cancer at Very Low Risk of Metastasis","LESS","Inclusion Criteria:\n\n1. Postmenopausal women: Postmenopausal status is defined by any of the following:\n\n   * Prior bilateral oophorectomy\n   * Age ≥60 years\n   * Age \\>50 and \\\u003C60 years and amenorrheic for at least 12 months, and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range\n2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1\n3. Women with histologically proven invasive unilateral breast cancer Note: In case of a multifocal invasive tumor, all lesions (maximum 3 infiltrating lesions allowed) must be of identical phenotype and low biological risk\n4. M0: Not clinically nor radiologically detectable metastases at time of inclusion\n5. Primary tumor completely resected and adequate axillary surgery performed, according to current standards\n6. IHC expression of the estrogen receptor and\u002For progesterone receptor ≥50%\n7. HER2 negative according to ASCO criteria in immunohistochemistry and\u002For genomic analysis (HER2 negativity is defined as IHC 0-1+, or \\[IHC 2+ and FISH or CISH nonamplified\\])\n8. No indication of adjuvant chemotherapy\n9. pT1 (tumor ≤20 mm), pN0, Grade 1 or Grade 2 OR pT2 (tumor ≤30 mm) and pN0, Grade 1 or Grade 2\n\n   Note 1: patient with Grade 2 pT2pN0 tumor must be aged under 70 years of age and should receive a genomic test as part of standard care (RIHN reimbursement)\n10. Patient considered has having a luminal A ultralow risk of metastatic recurrence (i.e.less than 5% risk of metastatic relapse at 10 years) according to MammaPrint® and Blueprint® tests.\n\n    Note 1: To be eligible, MammaPrint index score should be \\> +0.355\n11. Patients eligible to receive or have recently started (with a maximum of 4 months of adjuvant hormone therapy prior to enrollment) an adjuvant hormone therapy (letrozole, anastrozole, or exemestane)\n12. Patient is willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures\n13. Patients must be affiliated to a Social Security System (or equivalent)\n14. Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.\n\nExclusion Criteria:\n\n1. Patients who received a neo-adjuvant hormone therapy, a neo-adjuvant or adjuvant chemotherapy or preoperative medical treatment\n2. Any local or regional recurrence or metastatic disease\n3. Non-invasive carcinoma\n4. Bilateral breast cancer (except in case of contralateral DCIS), or history of other invasive ipsi- or contralateral breast cancer\n5. Patients with a history of another malignancy, except for properly treated cervical carcinoma in situ, and non-melanoma cancer of the skin\n6. Women with high-risk breast cancer predisposing deleterious germline mutations\n7. Contra-indications to the administration of anti-aromatase inhibitors\n8. Patients enrolled in another therapeutic study within 30 days prior to inclusion\n9. Patients with any other disease or illness, which requires hospitalization or is incompatible with the trial treatment\n10. Patients unwilling or unable to comply with trial obligations for geographic, social, physical or psychological reasons, or who are unable to understand the purpose and procedures of the trial\n11. Persons deprived of their liberty or under protective custody or guardianship","51 Years",{"count":522,"type":23},696,[58],"Hormone therapy is recommended for five years in all patients with hormone receptor-positive breast cancer, but there is no consensus on its duration in low-risk tumours and especially in postmenopausal women. Adjuvant endocrine therapy (ET) is associated with substantial side effects and long-term decreased quality of life.\n\nMoreover, while it has been shown that ET provides a real benefit in reducing the relapse rate over time, the deterioration in quality of life may also have a negative effect on patient adherence to treatment. It is therefore important to offer treatment to women with low-risk cancer less intensive treatment strategies. If recent trials tested longer durations as compared to 5 years for high-risk cancers, older trials have tested shorter durations. The 5-year duration appeared at that time as the gold standard because of optimal benefit-risk ratios of tamoxifen among high-risk patients. However shorter treatments of 2-3 years were already associated with substantial benefits and may be enough for very low risk patients.",[349],{"date":404,"type":37},{"date":528,"type":37},"2022-10-12",{"date":530,"type":23},"2035-11",{"name":43,"class":44},{"id":533,"slug":534,"hasResults":12,"nctId":535,"briefTitle":536,"officialTitle":537,"acronym":538,"eligibilityCriteria":539,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":540,"targetDuration":4,"studyType":24,"phases":542,"briefSummary":543,"conditions":544,"keywords":546,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":552,"lastUpdatePostDateStruct":553,"startDateStruct":554,"completionDateStruct":556,"leadSponsor":558,"locationsCount":4},"100648088","phase-3-rising-ctdna-to-tailor-endocrine-therapy-switch-in-patients-with-erher2--metastatic-breast-cancer-100648088","NCT07717450","Rising ctDNA to Tailor Endocrine Therapy Switch in Patients With ER+\u002FHER2- Metastatic Breast Cancer.","TAILORswitch (PADA-2): Rising ctDNA to Tailor Endocrine Therapy Switch in Patients With ER+\u002FHER2- Metastatic Breast Cancer.","TAILORswitch","Inclusion Criteria:\n\nRelated to Step #1\n\n1. First written informed consent (ICF#1) prior to any trial specific procedures. When the participant is physically unable to give his written consent, an impartial witness, independent from the investigator and the sponsor, can confirm in signing the participant's consent;\n2. Men or women ≥ 18 years of age;\n3. Eastern Cooperative Oncology Group performance status of 0 or 1;\n4. ER+ HER2- advanced (metastatic or locally advanced inoperable) breast adenocarcinoma (ER-positivity threshold: ≥10% tumor cells; HER2-negative tumour is defined as an immunohistochemical (IHC) score of 0 or 1+, or an IHC score of 2+ with negative in situ hybridization (ISH) (HER2\u002FCEP17 ratio \\\u003C2 or, for single probe assessment, HER2 copy number \\\u003C4, according to the most recent available results), not amenable to resection or radiation therapy with curative intent;\n5. Eligible to (per investigator assessment) or currently receiving for up to 3 years, AI (+\u002F- LH-RH agonist) and CDK4\u002F6i (palbociclib or ribociclib) as first line therapy with adequate cardiac, renal, hematological and hepatic functions per investigator assessment;\n6. Evaluable disease (RECIST v1.1) before the start of AI+CDK4\u002F6i and, in participants currently receiving AI and CDK4\u002F6i, no evidence of clinical or radiological progression since AI+CDK4\u002F6i initiation;\n7. Must have an adequate archival tumor tissue sample available (with a cellularity \\> 30%) for centralized WGS analysis to design the ctDNA test. Requirements:\n8. Pre\u002Fperimenopausal women and fertile men must agree to use adequate contraception methods during the study:\n\n   * Female participants must be using highly effective standard-of-care non-hormonal contraceptive measures from the time of screening until 3 weeks after exiting from Step #1 (a highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly); or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: (a) Post-menopausal, defined as women with: (i) Cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; (ii) Cessation of regular menses for at least 6 consecutive months with no alternative pathological or physiological cause AND with serum estradiol and follicle stimulating hormone level within the laboratory's reference range for post-menopausal females; (iii) Previous bilateral surgical oophorectomy.\n   * Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception until at least one week after the last treatment administration.\n9. Women of childbearing potential must have a negative serum or urine pregnancy test done within 28 days before inclusion;\n10. Minimum life expectancy of at least 6 months;\n11. Participants must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan and other study procedures including follow-up;\n12. Participants must be affiliated with a social security scheme or a beneficiary of such a scheme (or equivalent);\n\n    Additional criteria to be part of the imaging de-escalation sub-study in Step #1:\n13. Additional written informed consent (ICF#2). When the participant is physically unable to give his written consent, an impartial witness, independent from the investigator and the sponsor, can confirm in signing the participant's consent;\n14. Participants must have received at least 6 months (from 22 weeks authorized) of treatment with AI + CDK4\u002F6 inhibitor, with no evidence of ctDNA rising in STEP #1 (at the current visit or, if current results are pending, at the previous visit), and no disease progression on imaging at the current visit as per RECIST v1.1.\n15. ctDNA detected at study entry and no rising ctDNA;\n16. No history of venous thrombo-embolic event, interstitial lung disease or any pre-existing condition that may impair participant's respiratory function (per investigator assessment);\n17. Willingness and ability to comply with scheduled visits;\n\n    Related to Step #2:\n18. Additional written informed consent (ICF#3). When the participant is physically unable to give his written consent, an impartial witness independent from the investigator and the sponsor, can confirm in signing the participant's consent;\n19. Rising ctDNA (as defined in the protocol) detected during Step #1 (centrally determined);\n20. Having received at least 6 months of AI + CDK4\u002F6i;\n21. Adequate bone marrow reserve and organ function as follows:\n\n    1. Hemoglobin ≥9.0g\u002FdL (90 g\u002FL).\n    2. Absolute neutrophil count ≥1000\u002Fmm3 (1.0×10\\^9\u002FL) or documented institutional normal range for starting abemaciclib.\n    3. Total bilirubin ≤1.5×ULN or ≤3×ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia).\n    4. ALT and AST ≤3×ULN; for participants with hepatic metastases, ALT and AST ≤5×ULN.\n    5. Alkaline phosphatase ≤2.5×ULN (≤ 5.0×ULN if bone or liver metastases present).\n    6. Serum creatinine ≤ 1.5×ULN or calculated creatinine clearance ≥ 30 mL\u002Fmin as determined by Cockcroft-Gault (using actual body weight).\n22. Female participants must have a negative highly sensitive serum pregnancy test during the screening period if they are of childbearing potential and agree to use highly effective contraceptive methods to prevent pregnancy during the study and for 4 weeks following the last dose of camizestrant (if applicable) and\u002For for 3 weeks after the last dose of CDK4\u002F6inhibitor or must have evidence of nonchildbearing potential. In addition, female participants must refrain from egg cell donation and breastfeeding during this same period.\n\n    1. Non-sterilized male partners of a participant who is a woman of childbearing potential must use a male condom plus spermicide from the time of screening throughout the total duration of the study until 4 weeks after last dose of camizestrant.\n    2. Non-sterilised male participants (including males sterilised by a method other than bilateral orchidectomy, eg, vasectomy) who intend to be sexually active with a Female Of ChildBearing Potential (FOCBP) must be using an acceptable method of contraception, such as male condom plus spermicide (condom alone in countries where spermicides are not approved), from enrolment throughout the study until at least 1 week to avoid conception during treatment. Male participants must not donate or bank sperm during this same period.\n    3. Female partners (of child-bearing potential) of male participants enrolled in this study must also use a highly effective method of contraception from the time of study enrolment of their male partner, throughout their participation in the study, and until at least 1 week after their male partners last dose of camizestrant.\n\nExclusion Criteria:\n\nRelated to step #1:\n\n1. Systemic antineoplastic therapy (except adjuvant therapies) received prior to AI and CDK4\u002F6i;\n2. Known leptomeningeal metastasis and\u002For brain metastasis;\n3. Known contraindication to camizestrant and abemaciclib, per investigator assessment;\n4. Prior exposure to camizestrant, other SERD or investigational endocrine therapy agents;\n5. History of another malignancy, except (i) those treated with curative intent and with no known active disease ≥3 years; (ii) adequately treated non-melanoma cutaneous and in-situ cervix cancer;\n6. History of bone marrow transplantation;\n7. Patients relapsing while on or during the year after the discontinuation of adjuvant CDK4\u002F6 inhibitor.\n8. Pregnant women or women who are breast-feeding or participants not willing to apply highly effective contraception as defined in the protocol;\n9. Participants unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons;\n10. Participation in another clinical study whose procedures interfere with those of the study (within 28 days prior to participant enrolment and for the duration of the study);\n11. Persons deprived of their liberty or under protective custody or guardianship;\n\n    Related to step #2:\n12. Participants with synchronous disease progression per local assessment (tumor imaging performed within 28 days prior to entry in Step #2 RECIST v1.1);\n13. Participants with a contraindication to abemaciclib, as assessed by the investigator;\n14. Participants presenting any cardiovascular conditions (as described in the protocol)\n15. Participants treated within the last 2 weeks before randomization with medications that are sensitive substrates (e.g. omeprazole) or substrates with narrow therapeutic index of CYP2C9 and\u002For CYP2C19 (e.g. warfarin and phenytoin). Strong CYP3A4\u002F5 inducers should be stopped at least 2 weeks before randomization (3 weeks for St John's Wort).\n16. Participant who was treated within the timeframe indicated in the CSP with drugs that are known to prolong the QT interval.\n17. Participant taking medications known to prolong the QT interval and associated with a known risk of Torsades de Pointes\n18. Participant with a known active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), HBV (known positive HBsAg result), and HCV. Participants with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antigen \\[HBsAg\\] test and a positive hepatitis B core antibody \\[HBcAb\\] test, accompanied by a negative HBV DNA test) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA\n19. Participants known to be positive for HIV can be enrolled if they fulfil the criteria recommended by Food and Drug Administration (FDA) and ASCO guidelines (FDA Guidance, Uldrick et al 2017): CD4+ T-cell (CD4+) counts ≥350 cells\u002FµL, AND No history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections within the past 12 months (prophylactic antimicrobials allowed if no DDI or overlapping toxicities), AND On established anti-retroviral therapy (ART) for at least 4 weeks and have an HIV viral load less than 400 copies\u002FmL before enrolment. Effective ART is defined as a drug, dosage and schedule associated with reduction and control of the viral load",{"count":541,"type":23},370,[175],"Rationale:\n\nIn patients with metastatic breast cancer, fragments of tumor DNA called \"circulating tumor DNA\" or \"ctDNA\" can be detected in the blood. When the level of ctDNA increases, it often means that treatment is no longer effective and that the disease is likely to progress. Previous studies have shown that quickly changing hormone therapy as soon as a specific genetic anomaly (ESR1 mutation) is detected in the blood can improve outcomes for breast cancer patients. This monitoring also allows for earlier action against cells that are resistant to treatment. However, this mutation is only present in about 4 out of 10 women, which limits the use of this method to only some patients.\n\nUnlike previous approaches that targeted only the ESR1 mutation, the TAILORswitch study will assess a change in treatment following an increase in ctDNA, even in the absence of mutation, and before any other signs of disease progression. This change will include a new oral hormone therapy (camizestrant) combined with a targeted treatment that has shown benefits in cases of resistance (abemaciclib). This approach aims to intervene earlier in order to prevent disease progression.\n\nIn summary, TAILORswitch explores a new way to personalize treatment, using more sensitive blood monitoring tools to improve quality of life and patient outcomes.\n\nObjectives:\n\nThe primary objective of this trial is to demonstrate the efficacy of switching to camizestrant-abemaciclib combination therapy in patients with hormone-dependent metastatic breast cancer (ER+ HER2-) receiving targeted therapy combined with hormone therapy as first-line treatment, in cases where ctDNA levels increase without other signs of disease progression (clinical or radiological).\n\nSecondary objectives include:\n\n* The efficacy, safety, and tolerability of the treatment switch\n* The safety and feasibility of reducing the number of imaging exams in patients undergoing ctDNA monitoring every 3 months (optional substudy).\n\nTrial Design:\n\nTAILORswitch is a multi-step phase 3 randomized trial. Step 1 involves recruiting 370 patients with advanced or metastatic hormone-dependent breast cancer who are receiving CDK4\u002F6 inhibitor and aromatase inhibitor therapy as their first treatment.\n\nOptional: some patients included in Step 1 will be offered to participate in a sub-study to evaluate imaging follow-up de-escalation. These patients will be allocated in of the following groups:\n\n* Group A: maintenance of standard imaging every 3 to 4 months.\n* Group B: reduction to imaging once per year at most, with a return to the standard frequency in case of clinical, radiological, biological, or ctDNA-based signs of progression.\n\nStep 2 involves patients who are initially eligible and show an increase in ctDNA levels without radiological progression. These patients will be allocated to one of the following groups:\n\n* Group experimental: switch to the combination of camizestrant + abemaciclib until progression.\n* Group control: continuation of standard treatment (AI + CDK4\u002F6i) until progression.\n\nThe recruitment period is 30 months, with the aim of including 156 patients in Step 2. Each participant will be followed for 30 months after inclusion.",[545],"Metastatic Invasive Breast Cancer",[547,548,549,550,551],"ctDNA monitoring","ER+ HER2- advanced breast cancer","de-escalate serial tumor imaging","watch and switch","metastatic breast cancer","2026-07-16",{"date":404,"type":37},{"date":555,"type":23},"2026-09-25",{"date":557,"type":23},"2032-06-25",{"name":43,"class":44},{"id":560,"slug":561,"hasResults":12,"nctId":562,"briefTitle":563,"officialTitle":564,"acronym":565,"eligibilityCriteria":566,"healthyVolunteers":12,"sex":170,"minAge":567,"maxAge":4,"enrollmentInfo":568,"targetDuration":4,"studyType":24,"phases":569,"briefSummary":570,"conditions":571,"keywords":573,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":552,"lastUpdatePostDateStruct":576,"startDateStruct":578,"completionDateStruct":580,"leadSponsor":582,"locationsCount":583},"100641210","phase-2-skipping-hormone-therapy-in-low-risk-early-breast-cancer-100641210","NCT07661927","Skipping Hormone Therapy in Low-Risk Early Breast Cancer","No Endocrine Therapy in Small HR⁺\u002FHER2- Low Risk Luminal A Early Breast Cancer, a Single-arm De-escalation Trial","NoELA","Inclusion Criteria:\n\n* Postmenopausal (underwent bilateral oophorectomy or non-chemo induced amenorrhea for 12 or more months) female participant ≥60 years of age.\n* New diagnosis of invasive carcinoma of the breast (ductal, tubular or mucinous) with primary tumor ≤1 cm on microscopic exam with no evidence of nodal or distant metastatic disease.\n* Contralateral breast described as BI-RADS (Breast Imaging-Reporting And Data System) 1 or 2 in diagnostic imaging.\n* Negative axillary node involvement by sentinel node biopsy or axillary node dissection (pN0) or Clinically negative axillary node involvement (cN0) after mandatory ultrasound exploration without surgical exploration of the axilla if Breast Conservative Surgery (BCS) was performed.\n* Estrogen Receptor (ER) positive (≥ 50%) and Progesterone Receptor(PR) positive (\\> 20%), Ki67 low (≤15%) and HER2 negative (IHC or In Situ Hybridization approach) according to ASCO (American Society of Clinical Oncology) criteria.\n* Histological grade scored on the invasive component, 1 or 2 if pT1a or grade 1 if pT1b.\n* Treated by mastectomy or BCS with microscopically clear resection margins defined as \"no-ink on tumor\" or ≥1 mm for invasive and non-invasive disease or no residual disease on re-excision.\n* If BCS was performed, participants must have received or have scheduled adjuvant local radiotherapy (RT) within 3 months after surgery\n* No indication of adjuvant chemotherapy.\n* The participant is willing and able to comply with the protocol for the duration of the study, including scheduled visits, treatment strategy, laboratory tests and other study procedures.\n* Participants must be affiliated with a Social Security System (or equivalent).\n* The participant must have signed a written informed consent form before any trial-specific procedures. When the participant is physically unable to give written consent, an impartial witness of her choice, independent from the investigator or the sponsor, can confirm the participant's consent in writing.\n\nExclusion Criteria:\n\n* Have received any neo-adjuvant treatment, including hormone therapy and chemotherapy.\n* Have received or are eligible for adjuvant chemotherapy.\n* Absolute contraindication for RT in case of BCS or patients who were treated with partial breast irradiation.\n* Have been treated with mastectomy and with adjuvant radiotherapy received or scheduled.\n* Invasive lobular breast cancer.\n* Bilateral breast cancer or history of other invasive ipsi- or contralateral breast cancer.\n* Multifocal or multicentric disease.\n* Disease limited to microinvasion only (\\\u003C 1 mm).\n* Evidence of lymphovascular invasion.\n* History of non-breast cancer malignancies if not disease-free for \\> 5 years and considered low risk of recurrence except for treated carcinoma in situ of the cervix, endometrium or colon, melanoma in situ and basal or squamous cell carcinoma of the skin.\n* Non-malignant severe disease associated with a life expectancy \\\u003C 10 years.\n* Women with BRCA1, BRCA2 or other high-risk breast cancer predisposing deleterious germline mutations.\n* Enrolled in another therapeutic study within 30 days prior to inclusion.\n* Unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.\n* Persons deprived of their liberty or under protective custody or guardianship.","60 Years",{"count":204,"type":23},[58],"The goal of this clinical trial is to determine whether a selected population of women with early-stage, low-risk breast cancer can avoid hormone therapy without increasing their risk of relapse. It will also evaluate the prognosis of these participants compared to participants who received standard treatment with hormone therapy in another study, estimate the risk of specific recurrence, cardiovascular and bone health, and participants' quality of life.\n\nAll participants will have undergone surgery and possibly radiation therapy, but unlike standard care, they will not receive hormone therapy afterward. Participants will be enrolled for two years and followed for up to five years after the last participant is enrolled in the trial to monitor for long-term cancer recurrence.",[572],"Breast Cancer (Early Breast Cancer)",[574,575,503],"breast cancer","hormone therapy",{"date":577,"type":37},"2026-07-17",{"date":579,"type":37},"2026-07-06",{"date":581,"type":23},"2033-07-06",{"name":43,"class":44},41,{"id":585,"slug":586,"hasResults":12,"nctId":587,"briefTitle":588,"officialTitle":589,"acronym":590,"eligibilityCriteria":591,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":592,"targetDuration":4,"studyType":24,"phases":593,"briefSummary":594,"conditions":595,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":189,"lastUpdatePostDateStruct":599,"startDateStruct":600,"completionDateStruct":602,"leadSponsor":603,"locationsCount":104},"100646952","phase-2-study-to-evaluate-the-efficacy-of-zanzalintinib-in-the-treatment-of-relapsed-or-metastatic-adenoid-cystic-carcinomas-of-the-head-and-neck-100646952","NCT07682675","Study to Evaluate the Efficacy of Zanzalintinib in the Treatment of Relapsed or Metastatic Adenoid Cystic Carcinomas of the Head and Neck","ZANACC: Phase 2 Non-randomized Single Arm Study Evaluating Zanzalintinib in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma of the Head and Neck","ZANACC","Inclusion Criteria:\n\n* Patient must have signed a written informed consent form prior to any trial specific procedures\n* Patient ≥18 years of age on day of signing informed consent\n* Adenoid Cystic Carcinoma (histologically proven) originating from the head and neck region in relapse and\u002For metastatic, not suitable for local therapy\n* Subjects must have at least 1 lesion measurable per RECIST v1.1 Criteria, with MRI or CT-scan\n* Patients with significant disease progression diagnosed within 3 months prior to enrollment, defined by radiological progression according to RECIST 1.1 determined by the comparison of 2 CT scans or 2 MRIs separated by a maximum of 6 months.\n* Performance Status 0-1\n* Subjects must have biopsiable tumor at screening. The use of recent archived biopsy at screening could be discussed with the coordinating team if there was no treatment between the biopsy and the inclusion.\n* Recovery to baseline or ≤ Grade 1 severity (National Cancer Institute - common terminology criteria for adverse events version 6.0 \\[NCI-CTCAE v6.0\\]) from adverse events (AEs), including immune-related adverse events (irAEs), related to any prior treatments, unless AE(s) are clinically nonsignificant and\u002For stable on supportive therapy (eg, physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, ≤ Grade 2 hypomagnesemia, ≤ Grade 2 neuropathy are permitted).\n* Adequate bone marrow function within 14 days before first dose of study treatment (absolute neutrophil count \\> 1,500 cells\u002Fmm3, platelets \\> 100,000 cells\u002Fmm3, Hb \\> 9g\u002Fdl, INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.2 x upper limit of normal (ULN).\n* Adequate liver function within 14 days before first dose of study treatment (total bilirubin ≤ 1.5 x UNL (for subjects with Gilbert's disease ≤ 3 x ULN), AST, ALT and ALP ≤ 3 x UNL or \\\u003C 5 x UNL in case of hepatic metastasis).\n* Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 40 mL\u002Fmin (≥ 0.67 mL\u002Fsec) using the Cockcroft Gault equation.\n* Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg\u002Fmg (≤ 113.2 mg\u002Fmmol) creatinine\n* Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures\n* Patients must be affiliated to a Social Security System\n* Women of childbearing potential must have a negative serum β-HCG pregnancy test within 7 days and\u002For negative urine pregnancy test within 48 hours prior to the administration of the first study treatment. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \\> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \\\u003C 55 years-of-age must have a serum follicle stimulating hormone \\[FSH\\] level \\> 40 mIU\u002FmL to confirm menopause). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.\n* Sexually active fertile subjects and their partners must agree to use highly effective method of contraception during the course of the study and through 186 days after the last dose of zanzalintinib for women of childbearing potential (WOCBP) or through 96 days after the last dose of zanzalintinib for men (whichever is later). An additional contraceptive method, such as a barrier method (eg, condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.\n\nExclusion Criteria:\n\n* Prior treatment with zanzalintinib or with another inhibitor of VEGFR\n* Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.\n* Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.\n* Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.\n* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and\u002For surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment. Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed.\n* Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors ) and platelet inhibitors (eg, clopidogrel).\n\nAllowed anticoagulants are the following:\n\n1. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).\n2. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen.\n\nNote: Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer.\n\n* Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.\n* The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\n\n  a) Unstable of deteriorating cardiovascular disorders: i. Congestive heart failure New York Heart Association Class 3 or 4, class 2 or higher, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsades de pointes).\n\nii. Uncontrolled hypertension defined as sustained blood pressure (BP) \\> 140 mm Hg systolic or \\> 90 mm Hg diastolic despite optimal antihypertensive treatment.\n\niii. Stroke (including transient ischemic attack \\[TIA\\]), myocardial infarction, or other clinically significant arterial thrombotic and\u002For ischemic event within 6 months before first dose of study treatment.\n\niv. Pulmonary embolism (PE) or deep vein thrombosis (DVT) or other prior clinically significant venous events within 3 months before first dose of study treatment.\n\nNote: Subjects with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen.\n\nNote: Subjects who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the investigator.\n\nv. Prior history of myocarditis. b) Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. Tumors invading the GI-tract from external viscera ii. Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis iii. Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months before first dose unless cause of obstruction is definitively managed and subject is asymptomatic iv. Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.\n\nv. Known gastric or esophageal varices vi. Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks\n\n* Clinically significant hematuria, hematemesis, or hemoptysis of \\> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose of study treatment.\n* Symptomatic cavitating pulmonary lesion(s) or endobronchial disease (asymptomatic or radiated lesions allowed)\n* Lesions invading major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta.\n\nNote: Subjects with intravascular tumor extension (eg, tumor thrombus in renal vein or inferior V. cava) may be eligible following investigator approval.\n\n* Other clinically significant disorders that would preclude safe study participation.\n\n  1. Active infection requiring systemic treatment. Note: Prophylactic antimicrobial treatments (antibiotics, antimycotic, antiviral) are allowed.\n  2. Known infection with acute or chronic hepatitis B or C, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness except for subjects meeting all of the following criteria: (1) on stable anti-retroviral therapy; (2) CD4+ T cell count ≥ 200\u002FµL; and (3) an undetectable viral load. Note: HIV testing will be performed at screening if and as required by local regulation. Note: To be eligible, participants taking CYP inhibitors (eg, zidovudine, ritonavir, cobicistat, didanosine) or CYP3 inducers (efavirenz) must change to a different regimen not including these drugs 7 days prior to initiation of study treatment. Anti-retroviral therapies (ART) must have been received for at least 4 weeks prior to the first dose. Note: CD4+ T cell counts, and viral load are monitored per standard of care by the local health care provider.\n  3. Serious non-healing wound\u002Fulcer\u002Fbone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions.\n  4. Malabsorption syndrome.\n  5. Pharmacologically uncompensated, symptomatic hypothyroidism.\n  6. Moderate to severe hepatic impairment (Child-Pugh B or C).\n  7. Requirement for hemodialysis or peritoneal dialysis.\n  8. History of solid organ or allogeneic stem cell transplant.\n* Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to first dose of study treatment. Prior laparoscopic surgeries (ie nephrectomy) within 4 weeks prior to first dose of study treatment. Minor surgery (eg, simple excision, tooth extraction) within 5 days before first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to first dose of study treatment.\n\nNote: Fresh tumor biopsies should be performed at least 5 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible.\n\n\\- Corrected QT interval calculated by the Fridericia formula (QTcF) \\> 480 ms within 14 days per electrocardiogram (ECG) before first dose of study treatment.\n\nNote: Triplicate ECG evaluations will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility.\n\n* History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.\n* Inability to swallow tablets or ingest a suspension either orally or by a nasogastric (NG) or gastrostomy (PEG) tube.\n* Previously identified allergy or hypersensitivity to components of the study treatment formulations.\n* Another malignancy that requires active therapy and in the opinion of the Investigator would interfere with monitoring of radiologic assessments of response to Investigational Product, within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy. Incidentally diagnosed prostate cancer is allowed if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6.\n* Other conditions, which in the opinion of the Investigator, would compromise the safety of the patient or the patient's ability to complete the study.\n* Pregnant or breast-feeding women.\n* Person deprived of their liberty or under protective custody or guardianship",{"count":56,"type":23},[58],"Adenoid cystic carcinomas are rare cancers of the salivary glands. These cancers are treated with curative surgery, often followed by radiation therapy. Despite this aggressive treatment, approximately 50% of patients will develop a recurrence or metastatic disease (spread of the disease to another part of the body). Treatment of this progressive disease with chemotherapy or targeted therapy has not demonstrated significant efficacy so far, and there are currently no management recommendations from health authorities. The emergence of new drugs offers hope for patients. Zanzalintinib, thanks to its specific mechanisms of action, could be an effective treatment for patients whose disease has progressed.",[596,597,598],"Adenoid Cystic Carcinoma of the Salivary Gland","Recurrence","Metastatic Disease",{"date":579,"type":37},{"date":601,"type":23},"2026-10",{"date":434,"type":23},{"name":43,"class":44},{"id":605,"slug":606,"hasResults":12,"nctId":607,"briefTitle":608,"officialTitle":609,"acronym":610,"eligibilityCriteria":611,"healthyVolunteers":12,"sex":18,"minAge":54,"maxAge":4,"enrollmentInfo":612,"targetDuration":4,"studyType":24,"phases":614,"briefSummary":615,"conditions":616,"keywords":619,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":625,"lastUpdatePostDateStruct":626,"startDateStruct":628,"completionDateStruct":629,"leadSponsor":631,"locationsCount":4},"100614807","phase-3-liver-directed-chemotherapy-after-surgery-of-liver-metastases-of-colorectal-cancer-in-patients-with-high-risk-of-recurrence-of-their-disease-100614807","NCT07284394","Liver-directed Chemotherapy After Surgery of Liver Metastases of Colorectal Cancer in Patients With High Risk of Recurrence of Their Disease","Postoperative Hepatic Arterial Chemotherapy After Resection of Colorectal Liver Metastases in Patients at High Risk of Recurrence","PACHA-02","Inclusion Criteria:\n\n* Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent\n* Age \\> 18 years\n* ECOG performance status 0-1\n* Histologically confirmed stage IV pMMR CRC\n* Resected CRLM by one- or two-stage procedures including reverse strategy\n* Partial Response or Stability Disease (RECIST 1.1) to preoperative cytotoxic doublet or triplet IV chemotherapy +\u002F- targeted agent before surgery\n* Curative-intent ( R0\u002FR1 resection ± local ablation) surgery of 4 or higher CRLM\n* No macroscopic residual (hepatic or extra-hepatic) disease on postoperative CT scan within 4 weeks after surgery confirmed during local multidisciplinary tumor board (except up to 3 lung nodules \\\u003C 10 mm deemed amenable to curative-intent resection\u002Flocal ablation and non-resected primary tumor with no or mild symptoms)\n* Eligible to HAI of oxaliplatin by (permanent or selective) catheterization defined as the absence of medical (any contraindication to oxaliplatin administration, mainly residual peripheral sensory neuropathy grade \\\u003C 2) and technical (vascular anatomy to perform HAI chemotherapy) contraindications to administer oxaliplatin-based doublet or triplet chemotherapy within 8 weeks from surgery during at least 4 cycles evaluated by interventional radiologist and medical oncologist\n* Normal liver function (bilirubin \\\u003C 1.5 x upper limit of normal values (ULN), aminotransferases \\\u003C 5 ULN, alkaline phosphatase \\\u003C 5 ULN, International normalized ratio (INR) \\\u003C 1.5 ULN, platelets \\> 100,000\u002Fmm3)\n* Women of childbearing potential must have a negative pregnancy test done within 30 days before randomisation\n* Potentially reproductive patients must agree to use an effective contraceptive method or practice adequate methods of birth control or practice complete abstinence while on treatment, and for at least 6 months after the last dose of study drug\n* Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures\n* Patients must be affiliated to a Social Security System (or equivalent)\n\nExclusion Criteria:\n\n* Stage IV dMMR CRC\n* Progressive Disease (RECIST 1.1) to preoperative cytotoxic doublet or triplet IV chemotherapy +\u002F- targeted\n* Incomplete (R2) surgery or residual (hepatic or extrahepatic) disease on postoperative CT scan within 4 weeks after surgery or symptomatic primary tumours in case of reverse strategy\n* Extra hepatic metastasis disease, except ≤ 3 lung nodules \\\u003C 10 mm deemed amenable to curative-intent resection\u002Flocal ablation and non-resected primary tumor with no or mild symptoms\n* Impossibility to receive at least 4 postoperative cycles with oxaliplatin\n* Patients with contraindications for HAI or IV doublet or triplet administration as limiting anatomical variations of hepatic artery, peripheral sensory neuropathy ≥ grade 2 (NCI-CTAE v.5.0), gastric\u002Fduodenal ulcer or significant chronic liver disease (resulting in portal hypertension and\u002For liver failure)\n* Peripheral neuropathy grade ≥ 2\n* Patient with a dihydropyrimidine dehydrogenase deficiency (DPD)\n* Medical history of other concomitant or previous malignant disease, except adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, or cancer in complete remission for ≥5 years\n* Pregnant women or women who are breast-feeding\n* Participation in another therapeutic trial within the 30 days prior to randomisation\n* Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons\n* Persons deprived of their liberty or under protective custody or guardianship",{"count":613,"type":23},272,[175],"At the time of diagnosis, 25% of patients with colorectal cancer present with liver metastasis (CRLM). Among patients with localized colorectal cancer (Stages I-III), 50% to 70% will develop liver metastases during the course of their disease. Surgery in combination with intravenous (IV) chemotherapy represents the only chance of cure for selected patients by removing all liver metastases and treat residual microscopic disease by postoperative chemotherapy for 3 months. However, up to two-thirds of patients will experience a relapse, with about two-thirds of recurrences occurring in the liver.\n\nHepatic arterial infusion (HAI) chemotherapy has been proposed to improve the efficacy of chemotherapy by increasing the concentration of the drug in the liver. This treatment is currently administered by infusion through a specific catheter placed in the artery feeding the liver parenchyma, connected to a subcutaneous port-a-cath system. Several trials have shown that the administration of floxuridine or oxaliplatin via HAI combined with IV chemotherapy achieves a higher response rate compared to IV chemotherapy alone in patients with unresectable colorectal liver metastases. HAI chemotherapy has thus become an attractive therapeutic option for patients who underwent curative-intent surgery to reduce the risk of hepatic recurrence.\n\nThe investigators recently demonstrated in the PACHA-01 phase II randomized study a 47% decrease of hepatic recurrence risk by HAI of oxaliplatin compared to IV chemotherapy alone, despite a higher but manageable toxicity among 99 patients who underwent curative surgery considered at high risk of recurrence. Moreover, this study showed promising results in terms of time to recurrence and survival. Moreover, feasibility has improved in recent years with the development of non-invasive techniques for HAI.\n\nThe investigators propose to conduct the PACHA-02 trial to evaluate the efficacy in terms of disease-free survival of oxaliplatin administered via HAI in combination with IV chemotherapy after curative resection in patients with colorectal cancer at high risk of recurrence. A total of 272 patients who will undergo curative surgery for at least 4 CRLM with no residual disease on imaging performed within 4 weeks after surgery will be included. Patients will then be randomized to receive oxaliplatin-based chemotherapy either via HAI or IV combined with standard IV chemotherapy, every 2 weeks for at least 3 months.\n\nThe primary objective of this study will be to determine if the administration of oxaliplatin via HAI increases the time between treatment and disease recurrence compared to IV administration. The secondary objectives include overall survival, hepatic recurrence-free survival, safety, pattern of recurrence, and quality of life.",[617,618],"Colorectal Adenocarcinoma Metastatic in the Liver","Colorectal Cancer",[620,621,622,623,624],"hepatic arterial infusion chemotherapy","Colorectal cancer","Colorectal Liver metastases","High risk of recurrence","Surgery","2026-05-22",{"date":627,"type":37},"2026-05-26",{"date":406,"type":23},{"date":630,"type":23},"2035-01",{"name":43,"class":44},{"id":633,"slug":634,"hasResults":12,"nctId":635,"briefTitle":636,"officialTitle":637,"acronym":638,"eligibilityCriteria":639,"healthyVolunteers":12,"sex":170,"minAge":54,"maxAge":4,"enrollmentInfo":640,"targetDuration":4,"studyType":24,"phases":642,"briefSummary":643,"conditions":644,"keywords":645,"overallStatus":129,"whyStopped":4,"lastUpdateSubmitDate":625,"lastUpdatePostDateStruct":646,"startDateStruct":647,"completionDateStruct":649,"leadSponsor":651,"locationsCount":652},"100611182","phase-3-chemotherapy-de-escalation-in-hr--her2--intermediate-risk-early-breast-cancer-treated-with-adjuvant-ribociclib-100611182","NCT07237256","Chemotherapy De-escalation in HR +, HER2-, Intermediate-risk Early Breast Cancer Treated With Adjuvant Ribociclib","No Chemotherapy in Intermediate-risk HR+ HER2- Early Breast Cancer Treated With Ribociclib (LEE-011) in the Adjuvant Setting, a Non-inferiority Phase III Trial","NoLEEta","Inclusion Criteria:\n\n1. Patient must have signed a written informed consent prior to any trial-specific screening procedure.\n\n   Note: When the patient is physically unable to give their written consent, an impartial witness of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.\n2. Patient is ≥ 18 years old.\n3. Patient is female with known menopausal status at the time of randomization.\n\n   Post-menopausal status is defined as:\n   1. Patient underwent bilateral oophorectomy, or\n   2. Age ≥ 60 years, or\n   3. Age \\\u003C 60 years and either amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression) or Follicle-stimulating hormone (FSH) and plasma estradiol are in the postmenopausal ranges per local normal ranges.\n   4. If taking tamoxifen or toremifene and age \\\u003C60 years, then FSH and plasma estradiol level in postmenopausal ranges.\n4. The following criteria must be met for histologically confirmed invasive breast carcinoma, as determined by the local pathologist:\n\n   1. Pathological stage (8th edition of the AJCC), including pT2 pN0 Grade 3 or pT2 pN0 Grade 2 with Ki67≥20% or pT0-2 pN1 or pT3-4 pN0\n   2. ER-positive (with tumor cells showing ≥10% ER staining) and HER2-negative according to the most recent ASCO\u002FCAP guidelines.\n\n   Note: Multifocal and multicentric tumors are allowed if they meet the clinical stage II criteria of the 8th Edition of the AJCC. All tumors must be ER-positive and HER2-negative. Patients with bilateral invasive breast cancer (diagnosed simultaneously or within 6 months of each other) are eligible if all lesions tested on both sides are ER+ (ie, ≥10% positive stained cells) and HER2- AND adequate surgery has been performed in both breasts.\n5. Chemotherapy eligible per investigator decision, based on clinicopathological findings or the results of any genomic signature.\n6. Patient has no contraindication for the adjuvant endocrine therapy (ET) or chemotherapy in the trial and is planned to be treated with ET for 5 years (after randomization date) or more.\n7. Curative surgery for the invasive disease must have been performed with negative surgical margins within 12 weeks before randomization. If positive surgical margins, patients are eligible if revision surgery or other adequate local treatment (i.e local radiotherapy) is planned.\n8. Women of childbearing potential (CBP) must have a confirmed negative serum pregnancy test (β-hCG) before starting study treatment.\n9. Women of childbearing potential must agree to use one effective form of contraception during trial treatment and up to 21 days after the last dose of study drugs or longer, if required per standard of care;\n10. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 28 days prior to randomization.\n11. Adequate hematological, renal, and hepatic function, as outlined below:\n\n    1. Absolute neutrophil count (ANC) ≥1.5 x 10⁹\u002FL\n    2. Platelet count ≥100 x 10⁹\u002FL\n    3. Hemoglobin ≥9 g\u002FdL\n    4. Total bilirubin \\\u003C ULN. Patients with known Gilbert syndrome may be enrolled with total bilirubin ≤3 x ULN or direct bilirubin ≤1.5 x ULN\n    5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \\\u003C2.5 x ULN\n    6. Serum creatinine ≤1.5 mg\u002FdL or calculated creatinine clearance ≥60 mL\u002Fmin\u002F1.73m² (CKD-EPI equation (2021))\n    7. Potassium, total calcium (corrected for serum albumin), and magnesium should be within institutional normal limits or corrected to within normal limits using supplements before the first dose of study medication.\n12. Standard 12-lead ECG values assessed, as:\n\n    1. QTcF interval (QT interval using Fridericia's correction) at screening \\\u003C 450 milliseconds (msec)\n    2. Resting heart rate 50-100 beats per minute (determined from the ECG)\n13. Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.\n14. Absence of any psychological, familial or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.\n15. Patients must be affiliated to a Social Security System (or equivalent) based on local regulations.\n\nExclusion Criteria:\n\n1. Patient has received any neoadjuvant chemotherapy since her breast cancer diagnosis or has received any prior CDK4\u002F6 inhibitor.\n2. Breast cancer diagnosed while patient was receiving tamoxifen, raloxifene or aromatase inhibitors (AIs) for reduction in risk (\"chemoprevention\") of breast cancer and\u002For treatment for osteoporosis within the last 2 years prior to randomization.\n3. Patient with a known hypersensitivity to any of the excipients of ribociclib and\u002For ET (e.g. rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, and soy or peanut allergy).\n4. Patient with evidence or history of distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition), inflammatory breast cancer, breast cancer recurrence (local or distant) or a different primary breast cancer.\n5. Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 2 years before randomization. Note: Patients with adequately treated basal or squamous cell skin carcinoma or curatively resected cervical cancer in situ are eligible.\n6. Patients whose breast cancer is considered as endocrine therapy insensitive, as determined by investigator's opinion; this may include (but is not limited to) breast cancer classified as \" basal like \" by molecular signatures (if available in the patient file) and\u002For breast cancer with persistently high proliferation after pre-operative endocrine therapy.\n7. Patient has had major surgery within 14 days prior to study treatment initiation.\n8. Patient has known history of human immunodeficiency virus (HIV) infection (testing is not mandatory) whose antiretroviral therapy (ART) has a known strong CYP3A4 inhibitor with potential for DDI with ribociclib. Patients with HIV may be enrolled if they fulfil the criteria recommended by FDA and ASCO guidelines (FDA Guidance, Uldrick et al. 2017):\n\n   1. CD4+ T-cell (CD4+) counts ≥ 350 cells\u002FµL, AND\n   2. No history of AIDS-defining opportunistic infections within the past 12 months (prophylactic antimicrobials allowed if no drug-drug interactions or overlapping toxicities), AND\n   3. On established ART which is not a strong CYP3A4 inhibitor, for at least 4 weeks and have an HIV viral load less than 400 copies\u002FmL prior to enrolment. Effective ART is defined as a drug, dosage, and schedule associated with reduction and control of the viral load.\n9. Patient has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (testing is not mandatory).\n10. Clinically significant, uncontrolled heart disease and\u002For cardiac repolarization abnormality, including any of the following:\n\n    1. History of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft within 6 months prior to trial entry.\n    2. Documented cardiomyopathy.\n    3. Left Ventricular Ejection Fraction (LVEF) \\\u003C 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) (testing not mandatory)\n    4. Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\n\n       * Risk factors for Torsades de Pointes (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant\u002Fsymptomatic bradycardia.\n       * Concomitant medication(s) with a known risk to prolong the QT interval and\u002For known to cause TdP that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting trial treatment).\n       * Inability to determine the QTcF interval.\n    5. Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade Atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third degree AV block).\n    6. Uncontrolled arterial hypertension with systolic blood pressure \\>160 mmHg.\n11. Presence of any other medical conditions, including respiratory or metabolic dysfunction, physical examination findings, or laboratory results that raise reasonable suspicion of a contraindication to the use of an experimental drug, potential impact on compliance with the study protocol, influence on result interpretation, or increased risk of treatment complications for the patients (such as severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, preexisting Crohn's disease or ulcerative colitis, or a preexisting chronic condition resulting in clinically significant diarrhea).\n12. Previous history of pneumonitis, regardless of cause.\n13. Patient is currently receiving any of the following substances within 7 days before randomization and which cannot be stopped within seven days prior to the start of treatment:\n\n    1. Concomitant medications, herbal supplements, and\u002For fruits (e.g. grapefruit, pummelos, starfruit, Seville oranges) and their juices that are known as strong inhibitors or inducers of CYP3A4\u002F5\n    2. Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4\u002F5\n    3. Any medication prohibited according to the instructions for goserelin, leuprolide or triptorelin (pre-menopausal patients), anastrozole, exemestane, letrozole, or ribociclib.\n    4. Medications known to have a risk of prolonging the QT interval or causing Torsades de Pointes.\n14. Patient is concurrently using hormone replacement therapy. Estrogen replacement therapy discontinued less than two weeks prior to the start of treatment.\n15. Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting trial treatment, or has not fully recovered from side effects of such treatment.\n\n    Note: The following uses of corticosteroids are permitted: a short duration (\\\u003C5 days) of systemic corticosteroids; any duration of topical applications (e.g. for rash), inhaled sprays (e.g. for obstructive airways diseases), eye drops or local injections (e.g. intra-articular).\n16. Patient has any other concurrent severe and\u002For uncontrolled medical condition that would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, liver cirrhosis or any other significant liver disease, active untreated or uncontrolled fungal, bacterial or viral infections, active infection requiring systemic anti-bacterial therapy, etc.) or limit life expectancy to ≤5 years.\n17. Participation in other studies involving investigational drug(s) within 30 days prior to randomization or within 5 half-lives of the investigational drug(s) (whichever is longer), or participation in any other type of medical research judged not to be scientifically or medically compatible with this trial. If the patient is enrolled or planned to be enrolled in another study that does not involve an investigational drug, the agreement of the sponsor is required to establish eligibility.\n18. Inability or unwillingness to swallow oral pills.\n19. Presence of malabsorption syndrome or any other condition that could hinder the absorption of study drugs in the gastrointestinal tract.\n20. Any psychological, familial, sociological, or geographical factors that may impede adherence to the study protocol and follow-up schedule.\n21. Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the first 48 months of adjuvant therapy.\n22. Persons deprived of their liberty or under protective custody or guardianship.",{"count":641,"type":23},3902,[175],"The advent of CDK4\u002F6 inhibitors (drugs designed to block the action of CDK4\u002F6 proteins, which play a key role in cell proliferation) has improved treatment prospects for patients with metastatic breast cancer whose tumour cells express hormone receptors but not the HER2 protein (HR+\u002FHER2-). The NATALEE study showed that the addition of ribociclib for three years to conventional adjuvant hormone therapy (i.e. after surgery) prolonged survival free of invasive disease (i.e. extending to surrounding tissues) in patients with early HR breast cancer+ \u002FHER2-. Unlike other studies, NATALEE included a group of patients at intermediate risk of recurrence, usually treated with adjuvant chemotherapy before receiving hormone therapy. However, the benefit of adjuvant chemotherapy in these patients is uncertain. The hypothesis of the NoLEEta study is that by using the CDK 4\u002F6 inhibitor, patients could avoid adjuvant chemotherapy and therefore be spared the side-effects associated with this chemotherapy, without reducing the efficacy of the treatment.",[349],[323,325],{"date":627,"type":37},{"date":648,"type":37},"2025-12-18",{"date":650,"type":23},"2037-12-31",{"name":43,"class":44},138,{"id":654,"slug":655,"hasResults":12,"nctId":656,"briefTitle":657,"officialTitle":658,"acronym":659,"eligibilityCriteria":660,"healthyVolunteers":341,"sex":202,"minAge":661,"maxAge":4,"enrollmentInfo":662,"targetDuration":4,"studyType":24,"phases":664,"briefSummary":665,"conditions":666,"keywords":670,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":625,"lastUpdatePostDateStruct":675,"startDateStruct":676,"completionDateStruct":677,"leadSponsor":679,"locationsCount":4},"100556688","blood-biomarkers-based-screening-for-hpv-driven-opc-100556688","NCT06528353","Blood Biomarkers Based Screening for HPV-driven OPC","SCREEN-HPV: Blood Biomarkers Based Screening for HPV-driven OPC","SCREEN-HPV","Inclusion Criteria:\n\n* Aged ≥50 years from the general population\n* Man\n* No previous history of HPV-driven cancer or head neck cancer\n* Willingness to complete follow up visits\n\nExclusion Criteria:\n\n* Aged \\\u003C 50 years\n* Woman\n* History of HPV-driven cancer or head and neck cancer\n* Psychiatric conditions\n* Inability to complete follow up visits\n* Severe medical condition (life expectancy \\\u003C5 years)\n* Previous prophylactic HPV vaccination","50 Years",{"count":663,"type":23},10000,[26],"The objective of our study is to demonstrate that it is possible to detect and treat human papilloma virus (HPV)-related oropharyngeal cancers (OPC) early using simple blood tests. The success of this strategy will be evaluated by the number of participants positive for both HPV16-E6 serology and HPV circulating tumor DNA (ctDNA) whose early management has allowed the detection of a cancerous lesion and\u002For whose HPV ctDNA results have normalized after surgical intervention. If this study is conclusive, it could pave the way for the implementation of a national screening strategy for HPV-related OPC.",[667,668,669],"Head and Neck Squamous Cell Carcinoma","Anal Cancer","Human Papilloma Virus",[671,454,672,673,674],"HPV-induced cancer","virology","serology","secondary cancer prevention",{"date":627,"type":37},{"date":100,"type":23},{"date":678,"type":23},"2032-09",{"name":43,"class":44},""]