[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"MedSIR\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":340},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,12,0,[8,43,71,94,122,147,175,207,229,256,284,311],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":31,"lastUpdatePostDateStruct":32,"startDateStruct":35,"completionDateStruct":37,"leadSponsor":39,"locationsCount":42},"100553499","phase-2-safety-and-efficacy-of-t-dxd-vs-cdk46i-based-et-as-first-line-therapy-of-hr-positive-and-her2-lowultralow-advanced-breast-cancer-patients-classified-as-non-luminal-subtype-100553499",false,"NCT06486883","Safety and Efficacy of T-DXd vs. CDK4\u002F6i-based ET as First-line Therapy of HR-positive and HER2-low\u002FUltralow Advanced Breast Cancer Patients Classified as Non-luminal Subtype","A Randomized Phase II Study to Evaluate the Safety and Efficacy of Trastuzumab Deruxtecan Versus CDK4\u002F6 Inhibitor-based Endocrine Therapy as First-line Therapy of HR-positive and HER2-low\u002FUltralow Advanced Breast Cancer Patients Classified as Non-luminal Subtype According to Gene Expression Profiling.","PONTIAC","Inclusion Criteria:\n\n1. Patients must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.\n2. Female or male patients ≥ 18 years of age at the time of signing ICF.\n3. ECOG performance status of 0-1.\n4. Minimum life expectancy of ≥ 12 weeks at screening.\n5. Evidence of HER2-low expression (1+ by immunohistochemistry (IHC) or 2+ and negative by an in situ hybridization \\[ISH\\] test) or HER2-ultralow (IHC 0 with faint membrane staining and in ≤ 10% of tumor cells) breast cancer according to the most recent American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guidelines determined by a MEDSIR's designated central laboratory, using Ventana 4B5 antibody. This assessment has to be done on the most recently available (archived or newly collected) formalin-fixed, paraffin-embedded (FFPE) tumor tissue blocks (≤ 6 weeks or FFPE of a tumor sample obtained after last prior systemic therapy) from core or excisional biopsy from a locally recurrent (breast or locoregional lymph nodes) or metastatic tumor lesion, excluding bone metastases.\n6. Non-luminal breast cancer subtype as per central PAM50 analysis determined in the most recently available (archived or newly collected) FFPE tumor tissue blocks (≤ 6 weeks or FFPE of a tumor sample obtained after last prior systemic therapy) from core or excisional biopsy from a locally recurrent (breast or locoregional lymph nodes) or metastatic tumor lesion with the exception of bone metastases.\n7. Patients must have HR-positive (estrogen receptor \\[ER\\] and\u002For progesterone receptor \\[PgR\\]-positive defined as ≥ 1% positive stained cells) status according to the most recent ASCO\u002FCAP guidelines locally determined prior to study entry.\n8. Unresectable locally recurrent or metastatic breast cancer documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.\n9. Evaluable disease according to RECIST v.1.1. Patients with bone-only disease are not allowed. Patients with bone metastases with soft tissue masses measuring \\> 10 mm are eligible.\n10. Patients must have endocrine resistance criteria:\n\n    • disease progression during adjuvant ET or within the first year of completing adjuvant ET;\n\n    or endocrine sensitivity criteria:\n\n    • de novo metastatic disease or disease progression ≥ 12 months after completing adjuvant ET with at least one of the following requirements:\n    * Estrogen receptor ≤ 50% positive stained cells;\n    * and\u002For high histological grade or Ki67 \\> 50% on primary tumor;\n    * and\u002For liver metastases;\n    * and\u002For known non-luminal subtype as per local PAM50 analysis.\n11. No prior treatment with any systemic therapy for advanced disease.\n12. Patients treated with a CDK4\u002F6i in the adjuvant setting with a treatment-free interval (TFI) ≥ 12 months following CDK4\u002F6i treatment completion are eligible.\n13. Patients have adequate bone marrow, liver, and renal function:\n\n    * Hematological (without platelet, red blood cell transfusion, and\u002For granulocyte colony-stimulating factor support within 14 days before first study treatment dose): White blood cell (WBC) count \\> 3.0 x 109\u002FL, absolute neutrophil count (ANC) ≥ 1.5 x 109\u002FL, platelet count ≥ 100.0 x 109\u002FL, and hemoglobin ≥ 9.0 g\u002FdL (≥ 5.6mmol\u002FL).\n    * Hepatic: Serum albumin ≥ 2.5 g\u002FdL; total bilirubin ≤ 1.5 times upper limit of normal (x ULN) (≤ 3 x ULN in patients with liver metastases or know history of Gilbert's disease); alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver\u002For bone metastases); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN (≤ 5 x ULN in patients with liver metastases).\n    * Renal: Creatinine clearance ≥ 30 mL\u002Fmin as determined by Cockcroft Gault (using actual body weight).\n    * Coagulation: International normalized ratio or prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 × ULN.\n14. Resolution of all acute toxic effects of prior anti-cancer therapy to Grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v.5.0) (except for alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).\n15. Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 14 days before study treatment initiation. In addition, they must agree to use one highly effective method of birth control from the time of screening until 7 months after the last dose of T-DXd, or within the time period specified per local prescribing guidelines after the final dose of physician's choice of CDK4\u002F6i plus ET. Female patients must refrain from egg cell donation and breastfeeding during this same period.\n16. Male participants who are sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of screening until 4 months after the last dose of T-DXd, or within the time period specified per local prescribing guidelines after the final dose of physician's choice of CDK4\u002F6i plus ET. Male participants must not donate or bank sperm during this same period.\n17. Patients must be accessible for treatment and follow-up.\n\nExclusion Criteria:\n\n1. Current participation in another therapeutic clinical trial, except other translational studies.\n2. Treatment with approved or investigational cancer therapy within 3 weeks prior to initiation of study drug.\n3. Treatment with chloroquine\u002Fhydroxychloroquine within 14 days prior to initiation of study drug.\n4. Have previously been treated with T-DXd and\u002For fulvestrant. Note: patients who experienced relapse after more than 1 year from completion of fulvestrant are eligible.\n\n   Note I: previous treatment with anti-HER2 therapies in (neo-) adjuvant setting will be allowed for participants who showed conversion from HER2-positive expression in primary breast tumor sample to HER2-low or HER2-ultralow expression (HER2 loss) in relapsed tumor sample.\n5. Patients with advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions \\[pleural, pericardial, and\u002For peritoneal\\] and pulmonary lymphangitis).\n6. Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of CDK4\u002F6i, such as history of GI surgery which may result in intestinal blind loops and patients with clinically significant gastroparesis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease, or diarrhea of CTCAE Grade \\> 1.\n7. Known central nervous system (CNS) involvement (brain metastases and\u002For leptomeningeal carcinomatosis). Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy.\n8. Have a concurrent malignancy or malignancy within 5 years of study enrollment with the exception of carcinoma in situ of the cervix and basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.\n9. Known allergy or hypersensitivity reaction to any of the investigational medicinal products (IMPs) or their inactive ingredients.\n10. Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks prior to start of study treatment.\n11. Major surgical procedure or significant traumatic injury within 4 weeks before the first dose of study treatment or anticipation of need for major surgery within the course of the study treatment.\n12. Has an active cardiac disease or a history of cardiac dysfunction or conduction abnormalities including, but not confined, to any of the following:\n\n    * Participants with a medical history of myocardial infarction within 6 months before screening, symptomatic congestive heart failure (NYHA Class II to IV), unstable angina pectoris, or a recent (\\\u003C 6 months) cardiovascular event including stroke. Participants with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation to rule out myocardial infarction.\n    * Left ventricular ejection fraction (LVEF) \\\u003C 55% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO).\n    * History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, or ventricular tachycardia), which is symptomatic or requires treatment (NCI-CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers will be permitted to enroll.\n    * QT interval corrected by Fridericia's formula (QTcF) prolongation to \\> 470 ms (females) or \\> 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG).\n    * History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause Torsades de Pointes.\n    * Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.\n13. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months of the study enrolment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, post COVID-19 pulmonary fibrosis, etc.), and any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy (complete).\n14. Has a history of non-infectious interstitial lung disease (ILD)\u002Fpneumonitis that required steroids, has current ILD\u002Fpneumonitis, or has suspected ILD\u002Fpneumonitis that cannot be ruled out by imaging at screening.\n15. Pregnant or lactating women or patients not willing to apply highly effective contraception as defined in the protocol.\n16. Current known infection with hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients 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), and \\> 6 months off anti-viral treatment are eligible. Those participants should be closely monitored for HBV reactivation and have access to a local hepatitis B expert during and after the study.\n17. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.\n18. Patients with HCV co-infection or history of HCV co-infection.\n19. Patients with cirrhosis or fibrosis on prior imaging or biopsy.\n20. Has an active primary immunodeficiency or known human immunodeficiency virus (HIV) infection.\n21. Other active uncontrolled infection at the time of enrollment.\n22. Receipt of live or attenuated vaccine within 30 days prior to the first dose of study treatment.\n23. A history of uncontrolled seizures, CNS disorders, or serious and\u002For unstable pre-existing psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs or interfering with subject safety.\n24. Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be potent CYP3A4 inducers (for examples, see the Prohibited Medications Section).\n25. Known substance abuse or any other concurrent severe and\u002For uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation.\n26. Inability or unwillingness to comply with the requirements of the protocol in the opinion of the investigator.","ALL","18 Years",{"count":20,"type":21},200,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","This trial studies a type of advanced breast cancer defined as hormone receptor HR-positive\u002FHER2-negative and classified as non-luminal by gene expression profiling (PAM50). Patients will be treated with trastuzumab deruxtecan (T-DXd) or with physician's choice of CDK4\u002F6 inhibitor (CDK4\u002F6i) plus endocrine therapy (ET). The main purpose of the study is to analyze the efficacy of T-DXd in patients who have HR-positive and HER2-low\u002Fultralow advanced breast cancer classified as non-luminal subtype.",[27,28,29],"Advanced Breast Cancer","Advanced Breast Carcinoma","Hormone Receptor Positive Breast Carcinoma","RECRUITING","2026-06-01",{"date":33,"type":34},"2026-06-02","ACTUAL",{"date":36,"type":34},"2025-06-30",{"date":38,"type":21},"2028-01",{"name":40,"class":41},"MedSIR","OTHER",72,{"id":44,"slug":45,"hasResults":11,"nctId":46,"briefTitle":47,"officialTitle":48,"acronym":49,"eligibilityCriteria":50,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":51,"targetDuration":4,"studyType":22,"phases":53,"briefSummary":54,"conditions":55,"keywords":58,"overallStatus":63,"whyStopped":4,"lastUpdateSubmitDate":64,"lastUpdatePostDateStruct":65,"startDateStruct":66,"completionDateStruct":68,"leadSponsor":70,"locationsCount":4},"100639670","phase-2-a-phase-ii-study-of-zongertinib-plus-fulvestrant-in-participants-with-hr-positiveher2-negative-advanced-breast-cancer-harboring-her2-mutations-100639670","NCT07619066","A Phase II Study of Zongertinib Plus Fulvestrant in Participants With HR-positive\u002FHER2-negative Advanced Breast Cancer Harboring HER2 Mutations.","A Two-stage, Single-arm Phase II Study of Zongertinib Plus Fulvestrant in Participants With Hormone Receptor-positive\u002FHER2-negative Advanced Breast Cancer Harboring HER2 Mutations.","AGATHA","Inclusion Criteria:\n\n1. Participant, or legal representative (if applicable), must be capable to understand the purpose of the Study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.\n2. Female or male participants ≥ 18 years of age at the time of signing ICF.\n3. Pre- or perimenopausal women and men provided they are being treated with a LHRH analogue for at least 28 days (if shorter, post-menopausal levels of serum estradiol\u002Ffollicle-stimulating hormone \\[FSH\\] must be confirmed analytically) prior to initiation of the Study treatment, or post-menopausal women.\n4. Histologically- or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of either unresectable locally advanced or metastatic disease confirmed by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.\n5. Documentation of HR-positive (estrogen receptor \\[ER\\] and\u002For progesterone receptor \\[PgR\\] expression in ≥1% of tumor cells) and HER2-negative (0-1+ by immunohistochemistry \\[IHC\\] or 2+ and negative by in situ hybridization \\[ISH\\] test) tumor according to the most recent American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guidelines as per local assessment on the most recent analyzed biopsy.\n6. Known activating HER2 mutation.\n7. Measurable disease according to RECIST v.1.1.\n8. ECOG performance status of 0-1.\n9. Participants must have experienced disease progression after at least one line of endocrine therapy (including CDK4\u002F6 inhibitor). Participants who received CDK4\u002F6 inhibitor-based therapy in the adjuvant setting are also eligible provided that disease progression occurred after at least 12 months of treatment but within 12 months following completion of the CDK4\u002F6 inhibitor.\n10. Participants must not have received more than two prior chemotherapy regimens for advanced disease (an ADC is counted as one line of chemotherapy).\n11. No prior treatment with a HER2-directed tyrosine kinase inhibitor is permitted, but other HER2-targeted agents (such as T-DXd) and fulvestrant are allowed in any setting.\n12. Participants must have adequate bone marrow, liver, and renal function.\n13. Resolution of all acute toxic effects of prior anticancer therapy to grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 6.0 (v.6.0) (except for alopecia or other toxicities not considered a safety risk for the participant at investigator's discretion).\n14. Willing to provide biological samples.\n15. Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 7 days before Study treatment dose. In addition, they must agree to use one highly effective method of birth control from the time of screening until 2 years after the last dose of Study treatments. Female participants must refrain from egg cell donation and breastfeeding during this same period. Women who are nursing can be enrolled if they stop nursing. In this case, the patient cannot resume nursing until 30 days after the last dose of Study treatment.\n16. Male participants who are sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of screening until 2 years after the last dose of Study treatment. Male participants must not donate or bank sperm during this same period.\n17. Minimum life expectancy of ≥ 12 weeks at screening.\n\nExclusion Criteria:\n\n1. Participation in another clinical trial, interventional or observational, until the Study's safety visit. Note: Participation in retrospective studies or data analysis is allowed.\n2. Treatment with any approved or investigational cancer therapy within 21 days or 5 half-lives (whichever is shorter) prior to initiation of Study treatments, except for fulvestrant, which may be administered within a shorter interval.\n3. Participants who must or wish to continue the intake of restricted medication or any drug considered likely to interfere with the safe conduct of the trial.\n4. Known active uncontrolled or symptomatic central nervous system (CNS) metastases and\u002For leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and\u002For progressive growth.\n\n   Note: Participants with a history of CNS metastases are eligible if they have been previously treated with local therapy, are clinically stable, and off anticonvulsants and steroids for at least 14 days before the first dose of Study treatment.\n5. Have a concurrent malignancy or malignancy within 5 years of Study enrollment with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I endometrioid uterine cancer that have been previously treated with curative intent. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.\n6. Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) (zongertinib and fulvestrant) or their incorporated substances.\n7. History of malabsorption syndrome or any other condition that would interfere with enteral absorption in the opinion of the investigator (e.g., ongoing gastrointestinal obstruction\u002Fmotility disorder, malabsorption syndrome, nausea, vomiting, Crohn's disease, ulcerative colitis, chronic diarrhea, prior gastric bypass) or results in the inability or unwillingness to swallow pills.\n8. Radiotherapy within 2 weeks prior to the first dose of Study treatments, except palliative radiotherapy to regions other than the chest, which is allowed up to 1 week before the first dose of Study treatments.\n9. Major surgical procedure or significant traumatic injury within 14 days before the first dose of Study treatments or anticipation of need for major surgery within the course of the Study treatment.\n10. Clinically relevant cardiovascular\u002Fcerebrovascular disease and\u002For cardiac dysfunction or conduction abnormalities.\n11. Active or known pre-existing history of non-infectious interstitial lung disease (ILD)\u002Fpneumonitis that required steroids, or suspected ILD\u002Fpneumonitis that cannot be ruled out by imaging at screening.\n12. Coagulopathy or any history of coagulopathy within 6 months before Study enrollment, including history of deep vein thrombosis or pulmonary embolism. However, participants with the following conditions will be allowed to participate:\n\n    * Adequately treated catheter-related venous thrombosis occurring more than 28 days prior to Study entry.\n    * Treatment with an anticoagulant (e.g., warfarin or heparin) for a thrombotic event occurring more than 6 months before randomization, or for an otherwise stable and allowed medical condition (e.g., well controlled atrial fibrillation), provided dose and coagulation parameters (as defined by local standard of care) are stable for at least 28 days prior to Study entry. Due to the intramuscular route of administration, fulvestrant should be used with caution in patients with anticoagulant treatment.\n13. Participants with chronic hepatitis B virus (HBV) infection with active disease who meet the criteria for anti HBV therapy (according to local\u002Finstitutional standard) and who have not been treated with suppressive antiviral therapy prior to initiation of Study treatments or patients with a history of hepatitis C virus (HCV) infection who meet one or both of the following criteria:\n\n    * Currently receiving curative antiviral treatment.\n    * HCV viral load is above the limit of quantification (HCV RNA positive).\n14. Participants with history of human immunodeficiency virus (HIV) infection who meet one or more of the following criteria:\n\n    * CD4+ count \\\u003C 350 cells\u002FμL.\n    * Viral load \\> 400 copies\u002FμL (local lab assessment).\n    * Participants not receiving antiretroviral therapy, or who have received established antiretroviral therapy for less than 4 weeks prior to initiation of Study treatment.\n    * History of AIDS-defining opportunistic infections within 12 months prior to start of Study treatment.\n\n    Note: Participants with a history of HIV who do not meet any of the criteria above are eligible to participate but the patient must be under the care of a HIV\u002FInfectious Diseases specialist, or an HIV\u002FInfectious Diseases specialist must be consulted prior to inclusion.\n15. Other active uncontrolled infection at the time of enrollment.\n16. Participants with severe hepatic impairment (classified as Child-Pugh C or score 10-15).\n17. A history of uncontrolled seizures, CNS disorders, or serious and\u002For unstable pre-existing psychiatric disability judged by the Investigator to be clinically significant and adversely affecting compliance to Study treatment or interfering with participant's safety.\n18. Known substance abuse or any other concurrent severe and\u002For uncontrolled medical condition that would, in the investigator's judgment, contraindicate participant participation.\n19. Pregnant or lactating women or participants not willing to apply highly effective contraception as defined in the protocol.\n20. Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the Study\n21. Inability or unwillingness to comply with the requirements of the protocol in the opinion of the investigator.",{"count":52,"type":21},25,[24],"An international, multicenter, two-stage optimal Simon's design, single-arm phase II clinical trial to evaluate zongertinib plus fulvestrant combination therapy in participants with hormone receptor-positive\u002FHER2-negative advanced breast cancer harboring HER2 mutations.",[27,56,57],"Hormone Receptor Positive \u002F HER2-negative Breast Cancer","HER2 Mutation",[59,60,61,62],"HER2 mutations","Advanced breast cancer","endocrine therapy","HER2","NOT_YET_RECRUITING","2026-05-27",{"date":31,"type":34},{"date":67,"type":21},"2026-10-04",{"date":69,"type":21},"2028-11-28",{"name":40,"class":41},{"id":72,"slug":73,"hasResults":11,"nctId":74,"briefTitle":75,"officialTitle":76,"acronym":77,"eligibilityCriteria":78,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":79,"targetDuration":4,"studyType":22,"phases":81,"briefSummary":82,"conditions":83,"keywords":4,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":64,"lastUpdatePostDateStruct":86,"startDateStruct":88,"completionDateStruct":90,"leadSponsor":92,"locationsCount":93},"100607951","phase-2-efficacy-and-safety-of-camizestrant-plus-ribociclib-in-patients-with-breast-cancer-100607951","NCT07195227","Efficacy and Safety of Camizestrant Plus Ribociclib in Patients With Breast Cancer","Phase II Study to Evaluate the Efficacy and Safety of Camizestrant Plus Ribociclib in Patients With Hormone Receptor Positive (HR+) Breast Cancer","CADILLAC","Inclusion Criteria:\n\n1. Patient must be capable of understanding the purpose of the Study and have signed the written informed consent form (ICF) prior to beginning specific protocol procedures.\n2. Female or male patients ≥ 18 years of age at the time of signing ICF.\n3. Pre- or peri-menopausal women or men. are eligible if treated with a Luteinizing hormone-releasing hormone (LHRH) analogue. Treatment with a LHRH is recommended for at least 28 days prior to study treatment; if shorter, post-menopausal levels of serum estradiol\u002Ffollicle-stimulating hormone \\[FSH\\] must be confirmed analytically prior to Study enrollment.\n4. Post-menopausal women, defined by any of the following criteria:\n\n   * Cessation of menses for at least 12 consecutive months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.\n   * Documented bilateral surgical oophorectomy.\n5. Documented histologically confirmed HR+ and human epidermal growth factor receptor 2 (HER2)-negative breast cancer according to the most recent American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guidelines as per local assessment on the most recent analyzed biopsy. Therefore, tumors must be:\n\n   o HR+ defined as ≥ 10% of tumor cells stain positive for estrogen receptor (ER) on immunohistochemistry (IHC), and HER2- defined as 0 or 1+ intensity on IHC, or 2+ intensity on IHC and no evidence of amplification on in situ hybridization (ISH).\n6. Unresectable locally recurrent or metastatic disease confirmed by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.\n7. Patients must have received at least five years of adjuvant endocrine therapy, including at least two years of an AI (capped to 30% patients with treatment-free interval \\[TFI\\] ≥ 12 months.\n8. Patients must have:\n\n   * Radiological evidence of progression while on, or within 12 months of the end of (neo)adjuvant endocrine therapy (secondary endocrine resistance criteria), or\n   * Radiological evidence of progression more than 12 months of the end of (neo)adjuvant endocrine therapy (endocrine sensitive criteria).\n9. Patients receiving a CDK4\u002F6 inhibitor-based therapy in the (neo)adjuvant setting are eligible if disease progression is confirmed more than 12 months following CDK4\u002F6 inhibitor treatment completion in this scenario.\n10. Evidence of measurable disease as per RECIST v.1.1, or non-measurable, but evaluable, disease, including bone-only disease with at least one lytic or mixed lytic-blastic bone lesion.\n11. For patients receiving tamoxifen or toremifene, a washout period of 35 days (5 half-lives) prior to randomization is required\n12. Patients must agree to provide and have available a FFPE tissue biopsy sample taken at the time of presentation with recurrent or metastatic disease. If this is not available, archived primary breast cancer specimen may be submitted\n13. Adequate bone marrow and organ function:\n\n    * Hematological (without platelet, red blood cell transfusion, and\u002For granulocyte colony-stimulating factor support within seven days before treatment initiation): White blood cell (WBC) count \\> 3.0 x 109\u002FL; absolute neutrophil count (ANC) ≥ 1.5 x 109\u002FL; platelet count ≥ 100.0 x109\u002FL; and hemoglobin ≥ 9.0 g\u002FdL.\n    * Hepatic: Serum albumin ≥ 2.5 g\u002FdL; total serum bilirubin \\\u003C 1.5 x upper limit of normal (ULN) except for patients with Gilbert's syndrome who may be included if the total serum bilirubin is ≤ 3 x ULN or direct bilirubin ≤ 1.5 x ULN; alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 3 x ULN in patients with liver and\u002For bone metastases); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 x ULN (≤ 3 x ULN in patients with liver metastases); international normalized ratio (INR) \\\u003C 1.5. Prothrombin time (PT) or Prothrombin time-international normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT)\u002Fpartial thromboplastin time (PTT) ≤ 1.5 × ULN, except for subjects receiving coumarin-derivative anticoagulants, factor Xa inhibitors, or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator from product safety requirements (PSR).\n    * Renal: Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL\u002Fmin as calculated by Cockcroft- Gault equation.\n14. Patient must be available and willing to participate in the treatment and follow-up assessments as required.\n15. Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 14 days before Study treatment initiation. In addition, they must agree to use one highly effective method of birth control from the time of screening until 4 weeks after the last dose of Study treatments. Female patients must refrain from egg cell donation and breastfeeding during this same period. Non-sterilized male partners of heterosexually active females of childbearing potential participants must use a male condom from the time of enrollment of their female partner, throughout their participation in the Study, and until 4 weeks after their female partner's last dose of Study intervention.\n16. Male participants who are sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable highly effective method of contraception from the time of screening until 21 days after the last administration of the Study drug. Male participants must not donate or bank sperm during this same period. Female partners of childbearing potential of male participants must agree to use one highly effective method of contraception from the time of screening until 4 weeks after the last dose of Study treatments.\n17. ECOG performance status of 0-1.\n18. Minimum life expectancy of ≥ 6 months.\n\nExclusion Criteria:\n\n1. Formal contraindication to endocrine therapy defined as visceral crisis and\u002For rapidly or symptomatic progressive visceral disease.\n2. Current participation in another therapeutic clinical trial.\n3. Has previously been treated with any SERD, including camizestrant, experimental ETs or fulvestrant.\n4. Prior systemic therapy for advanced disease.\n5. Known active uncontrolled or symptomatic central nervous system (CNS) metastases and\u002For leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and\u002For progressive growth. Patients with a history of CNS metastases are eligible if they have been previously treated with local therapy, are clinically stable, and off anticonvulsants and steroids for at least 14 days before the first dose of Study treatment.\n6. History of another primary malignancy except for the following:\n\n   1. Malignancy treated with curative intent with no known active disease ≥ 3 years before the first dose of Study treatment, and of very low potential risk for recurrence.\n   2. Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease.\n   3. Other exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin.\n\n   Note: For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required.\n7. Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) or their incorporated substances.\n\n   Note: Ribociclib is contraindicated for patients with hypersensitivity\u002Fallergy to peanut or soya.\n8. History of malabsorption syndrome or other condition that would interfere with enteral absorption (ongoing gastrointestinal obstruction\u002Fmotility disorder, malabsorption syndrome, or prior gastric bypass) or results in the inability or unwillingness to swallow pills.\n9. Palliative radiotherapy with a limited field of radiation within two weeks or with wide field of radiation or radiation to more than 30% of the bone marrow within four weeks prior to Study enrollment.\n10. Major surgical procedure or significant traumatic injury within 14 days before Study enrollment.\n11. Known abnormalities in coagulation such as bleeding diathesis, or any history of coagulopathy within six months before Study enrollment, including history of deep vein thrombosis or pulmonary embolism.\n12. Pregnant or lactating women or patients not willing to apply highly effective contraception as defined in the protocol.\n13. Current known infection with human immunodeficiency virus (HIV) detectable viral load, hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients 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. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.\n14. Any other active uncontrolled infection at the time of screening. Known substance abuse or any other concurrent severe and\u002For uncontrolled psychiatric or medical condition that would, in the Investigator's judgment, contraindicate patient participation.",{"count":80,"type":21},150,[24],"This trial will study a type of breast cancer defined by the expression of hormone receptor in the cancer cells (HR+). Patients will be treated with ribociclib, a cyclin-dependent kinase inhibitor, and camizestrant, a selective estrogen receptor degrader (SERD) and complete ER antagonist. The main purpose of the Study is to analyze the efficacy (to find out how effective a treatment is) of ribociclib in combination with camizestrant in patients with advanced HR+ breast cancer who have received endocrine therapy (ET) in early breast cancer setting for at least 5 years, of which at least 2 years with aromatase inhibitor (AI). Ribociclib plus camizestrant efficacy will be determined by assessing the period from treatment initiation until disease progression, defined as progression free survival (PFS).\n\nThe anticipated favorable clinical benefits of the combination of ribociclib and camizestrant therapy are projected to outweigh the risks of this treatment. This Study will be performed in full compliance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and all applicable local Good Clinical Practice (GCP) and regulations.",[84,85],"Hormon Receptor Positive Breast Cancer","Breast Cancer",{"date":87,"type":34},"2026-05-29",{"date":89,"type":34},"2026-03-24",{"date":91,"type":21},"2028-03",{"name":40,"class":41},16,{"id":95,"slug":96,"hasResults":11,"nctId":97,"briefTitle":98,"officialTitle":99,"acronym":100,"eligibilityCriteria":101,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":102,"targetDuration":4,"studyType":22,"phases":104,"briefSummary":106,"conditions":107,"keywords":109,"overallStatus":63,"whyStopped":4,"lastUpdateSubmitDate":114,"lastUpdatePostDateStruct":115,"startDateStruct":117,"completionDateStruct":119,"leadSponsor":121,"locationsCount":4},"100630959","phase-1-phase-ibii-study-of-zanidatamab-plus-tucatinib-and-chemotherapy-in-her2-positive-advanced-breast-cancer-100630959","NCT07494448","Phase Ib\u002FII Study of Zanidatamab Plus Tucatinib and Chemotherapy in HER2-Positive Advanced Breast Cancer","Phase Ib\u002FII Study to Evaluate Safety and Preliminary Efficacy of Zanidatamab in Combination With Tucatinib and Chemotherapy (Capecitabine or Eribulin Mesylate) in HER2-Positive Advanced Breast Cancer","JAZMINE","Inclusion Criteria:\n\n1. Participants must be capable of understanding the purpose of the Study and have signed a written informed consent form (ICF) prior to beginning specific protocol procedures.\n2. Female or male participants ≥ 18 years of age at the time of signing the ICF.\n3. ECOG PS of 0-1.\n4. Minimum life expectancy of ≥ 12 weeks at screening.\n5. Unresectable locally advanced or metastatic disease documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.\n6. Locally confirmed HER2-positive breast cancer (immunohistochemistry \\[IHC\\] score of 3+ or ICH score of 2+ with confirmation of HER2 amplification by in situ hybridization \\[ISH\\]) per American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) 2018 criteria on the most recent analyzed biopsy.\n7. Evaluable disease by RECIST v.1.1.\n8. All participants need to have experienced disease progression after at least one line, but no more than 3 lines, of anti-HER2-therapy for advanced disease.\n9. Able to provide the most recently available FFPE tumor tissue blocks at the time of inclusion.\n\n   Note: If no archived sample is available participant eligibility should be discussed with the Medical Monitor.\n10. Able to provide blood samples at the established time points.\n11. Participant must have adequate bone marrow, coagulation, liver, and renal function:\n\n    * Absolute neutrophil count (ANC) ≥ 1.5 × 103\u002FμL, platelet count ≥ 100 x 103\u002FμL, and hemoglobin (Hgb) ≥ 9 g\u002FdL. Transfusion must be ≥ 14 days prior to starting therapy to establish adequate hematologic parameters independent of transfusion support. Participants with chronic anemia (other than autoimmune hemolytic anemia) that is supported by intermittent red blood cell transfusions are eligible.\n    * International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × the upper limit of normal (ULN), unless on medication known to alter INR and aPTT (Note: Warfarin and other coumarin derivatives are prohibited).\n    * Total bilirubin ≤ 1.5 × ULN or ≤ 3.0 × ULN for participants with Gilbert's disease (if the conjugated bilirubin is ≤ 1.5 × ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN (for participants with liver metastases, AST and ALT ≤ 5.0 × ULN are acceptable).\n    * Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL\u002Fmin calculated per institutional guidelines.\n12. Female participants of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of Study treatments.\n\n    Note: A woman is considered of childbearing potential, i.e., fertile, following menarche until post-menopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A post-menopausal state is defined as no menses for 12 months without an alternative medical cause. For participants with a hormonal profile compatible with menopausal status, they will be discussed with the medical monitor.\n13. Female participants of childbearing potential and male participants with a partner of childbearing potential must agree to use two methods of birth control with a failure rate of less than 1% per year starting at the screening, throughout the study, and for 12 months after the last dose of Study treatments.\n\n    Note: See Section 8.4.2 for allowed contraceptive methods.\n14. Female participants must refrain from oocyte donation and breastfeeding, and male participants must not donate or bank sperm starting at the screening, throughout the study, and for 12 months after the last dose of Study treatments.\n15. Participants must be accessible for treatment and follow-up visits.\n\nSpecific inclusion criteria for BMs:\n\n1. Stable BMs were defined as BMs radiographically stable for ≥4 weeks since completion of treatment.\n2. Untreated BM without immediate need for local therapy. For participants with untreated CNS lesions \\> 2.0 cm on screening contrast brain MRI, discussion with and approval from the medical monitor is required prior to enrollment.\n3. BMs that had progressed since local CNS therapy, with no clinical indication for immediate retreatment with local therapy.\n4. Washout periods before the first day of dosing were \\>7 days for SRS or gamma knife, and \\>24 days for WBRT, respectively. The use of systemic corticosteroids for control of symptoms of BM is not permitted if the total daily dose is \\> 2 mg of dexamethasone (or equivalent). However, participants on a chronic stable dose of ≤ 2 mg total daily of dexamethasone (or equivalent) may be eligible following discussion and approval by the medical monitor. Participants receiving an anticonvulsant therapy must be on stable dosing regimen for ≥ 14 days prior to the first dose of Study treatment.\n\nSpecific inclusion criteria for phase II At least 50% of participants enrolled in phase II must have BMs.\n\nExclusion Criteria:\n\n1. Participation in another clinical trial, interventional or observational, until the Study's safety visit.\n\n   Note: Participation in retrospective studies or data analysis is allowed.\n2. Have received treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS radiation, or experimental agent within ≤ 3 weeks prior to the first dose of Study treatments.\n\n   Note: For palliative non-CNS radiotherapy, a shorter washout period may be acceptable. This should be evaluated on a case-by-case basis and discussed with the medical monitor.\n3. Prior treatment with capecitabine and eribulin.\n4. Known or suspected leptomeningeal disease (LMD) as documented by the investigator.\n5. Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term (including massive uncontrolled effusions \\[pleural, pericardial, peritoneal\\] or pulmonary lymphangitis).\n6. Receipt of a live vaccine within 4 weeks prior to enrollment.\n7. History of prior allogeneic bone marrow, stem cell, or solid organ transplantation.\n8. The washout periods for prior anticancer therapies before randomization are as follows:\n\n   * Prior therapies with chemotherapy and\u002For monoclonal antibodies including ADCs: washout period up to 3 weeks.\n   * Prior therapies with small molecule targeted therapies: washout period of ≤ 2 weeks or 5 half-lives, whichever is shorter.\n   * No washout period needed for endocrine therapy.\n   * No washout period for gonadotropin-releasing hormone agonists.\n9. Requirement for ongoing therapy with any prohibited medications listed in the protocol.\n\n   Note: Refer to the prescribing information for each of the Study drugs for any additional prohibited concomitant medications.\n10. Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) or their incorporated substances, including life-threatening hypersensitivity to monoclonal antibodies or excipients in zanidatamab.\n11. Ongoing, clinically significant toxicity associated with prior cancer therapies that has not resolved to ≤ Grade 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v.5.0) (except for alopecia or other toxicities not considered a safety risk for the participant at the investigator's discretion).\n12. Has a concurrent malignancy or malignancy within 5 years of Study enrollment except for carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's medical monitor is required.\n13. Major surgical procedure or significant traumatic injury within 4 weeks before the first dose of Study treatment or anticipation of the need for major surgery within the course of the Study treatment.\n14. Have clinically significant cardiac disease such as:\n\n    * Ventricular arrhythmia requiring therapy.\n    * Uncontrolled hypertension (defined as persistent systolic blood pressure \\> 150 mm Hg and\u002For diastolic blood pressure \\> 100 mm Hg on antihypertensive medications).\n    * Any history of symptomatic congestive heart failure (CHF) classified as New York Heart Association (NYHA) Class II to IV, or any Grade ≥2 CHF related to prior therapy. Participants with Grade 1 CHF from prior treatment are eligible only if the condition has fully resolved at the time of screening.\n    * Presence of ≥ Grade 2 QTc prolongation on screening electrocardiogram (ECG).\n    * Conditions potentially resulting in drug-induced prolongation of the QT interval or torsade de pointes:\n\n      1. Congenital or acquired long QT syndrome.\n      2. Family history of sudden death.\n      3. History of previous drug induced QT prolongation.\n      4. Current use of medications with known and accepted associated risk of QT prolongation.\n    * Myocardial infarction or unstable angina within 6 months prior to first dose of study treatment.\n    * Left ventricular ejection fraction (LVEF) \\\u003C 50% as determined by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) documented within 4 weeks prior to first dose of Study treatments.\n15. Having a history of non-infectious interstitial lung disease (ILD)\u002Fpneumonitis that required steroids, has current ILD\u002Fpneumonitis, or has suspected ILD\u002Fpneumonitis that cannot be ruled out by imaging at screening.\n16. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months of the Study enrolment, severe asthma, severe chronic obstructive pulmonary disease \\[COPD\\], restrictive lung disease, pleural effusion, post COVID-19 pulmonary fibrosis, etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.\n17. Having peripheral neuropathy ≥ Grade 2.\n18. Known history of clinically significant bleeding, thrombosis, intestinal obstruction, or gastrointestinal perforation within 3 months of study initiation.\n19. Known active infection with hepatitis B virus (HBV) or hepatitis C virus (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 the polymerase chain reaction (PCR) is negative for HCV RNA.\n20. Known infection with Human Immunodeficiency Virus (HIV). I. Note: Participants with HIV on antiretroviral therapy (ART) with well-controlled HIV infection\u002Fdisease are allowed.\n\n    II. Participants on ART must have a CD4+ T-cell count ≥ 350 cells\u002Fmm3 at time of screening.\n\n    III. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies\u002FmL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening.\n\n    IV. Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to Study entry.\n\n    V. The combination of the ART regimen must not contain any medications that may interfere with the Study treatments.\n21. Other systemic uncontrolled infection at the time of enrollment.\n22. Having known dihydropyridine dehydrogenase deficiency (DPD). This must be checked before treatment with capecitabine, according to current guidelines.\n23. Having an inability to swallow pills or significant gastrointestinal disease, which would preclude the adequate oral absorption of medications.\n24. Any other serious medical condition and\u002For abnormality in clinical laboratory tests that, in the Investigator's judgment, precludes the participant's safe participation in and completion of the Study.\n\nSpecific exclusion criteria for phase II\n\n• Prior treatment with HER2 tyrosine kinase inhibitors (TKIs).",{"count":103,"type":21},24,[105,24],"PHASE1","The JAZMINE study is a multicenter, open-label, non-comparative, phase Ib\u002FII clinical trial to evaluate safety and preliminary efficacy of zanidatamab in combination with tucatinib and chemotherapy (capecitabine or eribulin mesylate) in HER2-positive advanced breast cancer.",[108,85],"HER 2 Positive Advanced Breast Cancer",[110,111,112,100,113],"Advanced HER 2 positive","Zanidatamab","Tucatinib","Chemotherapy","2026-04-20",{"date":116,"type":34},"2026-04-23",{"date":118,"type":21},"2026-07-01",{"date":120,"type":21},"2028-05-31",{"name":40,"class":41},{"id":123,"slug":124,"hasResults":11,"nctId":125,"briefTitle":126,"officialTitle":127,"acronym":128,"eligibilityCriteria":129,"healthyVolunteers":11,"sex":130,"minAge":18,"maxAge":4,"enrollmentInfo":131,"targetDuration":4,"studyType":22,"phases":133,"briefSummary":134,"conditions":135,"keywords":4,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":139,"lastUpdatePostDateStruct":140,"startDateStruct":142,"completionDateStruct":144,"leadSponsor":145,"locationsCount":146},"100529944","phase-2-niraparib-rechallenge-after-surgery-in-ovarian-cancer-patients-with-oligometastatic-progression-100529944","NCT06180356","Niraparib Rechallenge After Surgery in Ovarian Cancer Patients With Oligometastatic Progression","Phase II Study to Assess the Efficacy of Niraparib Rechallenge After Surgery in Ovarian Cancer Patients With Oligometastatic Progression (The ANALLISA Study)","ANALLISA","Inclusion Criteria:\n\n1. Written informed consent form (ICF) prior to beginning specific protocol procedures.\n2. Female patients ≥ 18 years of age.\n3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n4. Patients must have a life expectancy ≥16 weeks.\n5. Histologically confirmed high grade serous or endometrioid OC who have an OMP during or after the first maintenance therapy with any PARPi.\n6. Oligometastatic progression defined as 1-5 lesions (according to European Society for Radiotherapy and Oncology \\[ESTRO\\] and American Society for Radiation Oncology \\[ASTRO\\] consensus).\n\n   Note: Metastatic lymph nodes located within the same anatomical lymph-node chain or station, as confirmed on surgical specimen, shall be counted collectively as one single metastatic lesion.\n7. Patients must have undergone secondary cytoreductive surgery with centrally confirmed no evidence of macroscopic residual tumor after surgery (complete resection).\n8. Patients with asymptomatic and treated brain metastases are allowed if:\n\n1\\. Neurosurgical resection ≥ 28 days prior to initiation of study treatment. 2. Not requiring radiotherapy. 3. Not receiving steroid therapy or anticonvulsant for at least 7 days before the first dose of study treatment.\n\n9\\. Documented breast cancer gene 1\u002F2 (BRCA1\u002F2) status and\u002For homologous recombination (HR) status.\n\nNote I: Patients with germline or somatic mutations in the BRCA1 or BRCA2 genes will be considered with the HR status known and classified as with homologous recombination deficiency (HRD).\n\nNote II: HR test must be performed before C1D1.\n\n10\\. Patients who have received prior PARPi monotherapy or PARPi together with bevacizumab as maintenance treatment.\n\n11\\. Patients should have had benefit of prior PARPi defined by treatment for ≥12 months from initiation of PARPi maintenance until the date of OMP or have experienced tumor progression after treatment completion. Tumor progression must have been confirmed by computed tomography (CT) and\u002For PET-CT scan.\n\n12\\. If prior treatment was niraparib, no significant toxicity that led to treatment discontinuation.\n\n13\\. Willingness to provide formalin fixed, paraffin embedded (FFPE) tumor tissue from primary, if available, and secondary surgeries and blood samples at the time of the inclusion, every 12 weeks, and at the end of treatment (EoT).\n\n14\\. Able to take oral medications. 15. Patients must start treatment 3 to 8 weeks from surgery, once recovered from surgery.\n\n16\\. Women of childbearing potential who engage in heterosexual intercourse must agree to use institution specified method(s) of contraception and must refrain from donating eggs in the time period specified in the study protocol. Women of childbearing potential must have a negative serum or a highly sensitive urine pregnancy test within 72 hours before study treatment initiation.\n\n17\\. Patient has adequate bone marrow, liver, and renal function:\n\n* Hematological: White blood cell (WBC) count \\> 3.0 x 109\u002FL, absolute neutrophil count (ANC) ≥ 1.5 x 109\u002FL, platelet count ≥ 100.0 x109\u002FL, and hemoglobin ≥ 9.0 g\u002FdL (≥ 5.6 mmol\u002FL).\n* Hepatic: total bilirubin ≤ institutional upper limit of normal (ULN) (except for Gilbert's syndrome); alkaline phosphatase (ALP) ≤ 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 times ULN. 11).\n* Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL\u002Fmin\u002F1.73 m2 for patients with creatinine levels above institutional normal.\n\n  18\\. Patients must be accessible for treatment follow-up.\n\nExclusion Criteria:\n\n1. Patients with symptomatic or systemic progressive disease not fulfilling OMP disease criteria.\n2. Patients with residual disease after secondary cytoreductive surgery.\n3. Patients with persistent toxicities (\\> Common Terminology Criteria for Adverse Events (CTCAE) grade 2) caused by previous cancer therapy.\n4. Patients unable to swallow oral medication or with any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of niraparib, or put the study outcomes at undue risk.\n5. Patients with clinically significant cardiovascular disease such as uncontrolled hypertension, uncontrolled or symptomatic arrythmias, congestive heart failure (CHF), or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association (NYHA) Functional Classification.\n6. Patients treated with previous PARPi therapy who have any known, persistent (\\>4 weeks), ≥Grade 3 anemia, neutrophil count decrease or platelet count decrease.\n7. Patients with known history of human immunodeficiency virus (HIV), or active hepatitis C Virus (HCV), or active hepatitis B Virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics.\n8. Patients with known hypersensitivity or allergy to prior niraparib treatment or any of the excipients of the product.\n9. Patients who have received a transfusion of platelets or red blood cells, colony-stimulating factors or have any other laboratory abnormality within 2 weeks prior niraparib treatment that might confound or interfere with the study result.\n10. Participation in another clinical trial, interventional or observational, until the Study's safety visit.\n\n    Note: participation in retrospective studies or data analysis is allowed.\n11. Patients who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study treatment.\n12. Patients with myelodysplastic syndrome (MSD)\u002FAcute myeloid leukemia (AML), with history of MSD\u002FAML or with features suggestive of MDS\u002FAML.\n13. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).\n14. Other malignancy unless curatively treated with no evidence of disease ≥ 5 years prior to study enrollment. Note: Patients with adequately non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) and stage 1 low grade endometrial carcinoma are not excluded.\n15. Vaccination with any live virus vaccine within 28 days prior study treatment initiation.","FEMALE",{"count":132,"type":21},30,[24],"The ANALLISA study is a fast, proof-of-concept, phase II clinical trial which aims to assess the efficacy of niraparib rechallenge treatment after secondary cytoreductive surgery in ovarian cancer (OC) patients with oligometastatic progression (OMP) after first maintenance therapy with any PARP inhibitor. A total of 30 patients with OC and OMP will be enrolled and will receive treatment with niraparib 300 or 200 mg, according to body weight or platelet count. Patients will start treatment within 8 weeks after surgery and will receive it until progressive disease or treatment discontinuation. The main purpose of the study is to evaluate progression-free survival (PFS) of niraparib rechallenge in OC patients with OMP and no residual disease after secondary cytoreductive surgery.",[136,137,138],"Ovarian Cancer","Oligometastatic Disease","Serous Ovarian Tumor","2026-04-17",{"date":141,"type":34},"2026-04-22",{"date":143,"type":34},"2024-12-03",{"date":38,"type":21},{"name":40,"class":41},14,{"id":148,"slug":149,"hasResults":11,"nctId":150,"briefTitle":151,"officialTitle":151,"acronym":152,"eligibilityCriteria":153,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":154,"targetDuration":4,"studyType":156,"phases":4,"briefSummary":157,"conditions":158,"keywords":160,"overallStatus":63,"whyStopped":4,"lastUpdateSubmitDate":167,"lastUpdatePostDateStruct":168,"startDateStruct":170,"completionDateStruct":172,"leadSponsor":174,"locationsCount":4},"100632612","a-comprehensive-biomarker-evaluation-in-biliary-tract-cancer-100632612","NCT07515950","A COMPREHENSIVE BIOMARKER EVALUATION IN BILIARY TRACT CANCER","REVEAL-BTC","Inclusion Criteria:\n\n1. Written informed consent for the use of clinical data and tissue samples is available. (The use of data and samples without consent is only possible if exemption is granted by the corresponding Institutional Review Board - IRB).\n2. Histologically confirmed diagnosis of biliary tract cancer (including gallbladder carcinoma \\[GBC\\] or cholangiocarcinoma \\[CCA\\]), regardless of disease stage.\n3. Diagnosis must have been established within the last 15 years prior to Study initiation.\n4. Availability of archival formalin-fixed paraffin-embedded (FFPE) tumor tissue sample, collected prior to Study inclusion at any disease stage (e.g., during surgery or in the advanced setting). For patients with de novo metastatic disease or early stage primary tumors undergoing surgery, the tissue must have been obtained before the initiation of any systemic therapy (e.g. chemotherapy) or radiotherapy. For patients with recurrent disease undergoing a new biopsy, previous treatments are allowed.\n5. Availability and accessibility of basic clinical information and survival data on medical records.\n\nExclusion Criteria:\n\n1. Unavailability or inadequate quality (e.g., insufficient tumor content, degraded tissue) of archival FFPE tumor tissue samples for the planned immunohistochemical analysis.\n2. Missing or incomplete basic clinical and\u002For survival data in the medical record.",{"count":155,"type":21},244,"OBSERVATIONAL","The REVEAL-BTC Study will analyze 5 biomarkes in samples of participants who in the past 15 year have been diagnosed with any stage of biliary tract cancer. The expression levels of the biomarkers will be correlated with clinical outcomes in the participants, which will lead to better patient stratification that will help guide the use of targeted therapies in the future.",[159],"Biliary Tract Cancer (BTC)",[161,162,163,164,165,166],"Biliary tract cancer","CLDN18.2","TROP2","B7-H4","HER-2","PD-L1","2026-03-31",{"date":169,"type":34},"2026-04-07",{"date":171,"type":21},"2026-07",{"date":173,"type":21},"2027-07",{"name":40,"class":41},{"id":176,"slug":177,"hasResults":11,"nctId":178,"briefTitle":179,"officialTitle":180,"acronym":181,"eligibilityCriteria":182,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":183,"targetDuration":4,"studyType":22,"phases":185,"briefSummary":187,"conditions":188,"keywords":192,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":198,"lastUpdatePostDateStruct":199,"startDateStruct":201,"completionDateStruct":203,"leadSponsor":205,"locationsCount":206},"100545518","phase-3-elacestrant--everolimus-in-patients-erher2--esr1mut-advanced-breast-cancer-progressing-to-et-and-cdk46i-100545518","NCT06382948","Elacestrant + Everolimus in Patients ER+\u002FHER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4\u002F6i.","A Randomized Phase 3, Double-Blind, Placebo-Controlled Study of Elacestrant Plus Everolimus Versus Elacestrant in Patients With ER+\u002FHER2-, ESR1mut Advanced Breast Cancer Progressing to Endocrine Therapy and CDK4\u002F6 Inhibitors","ADELA","Inclusion Criteria:\n\nPatients will be included in the study only if they meet ALL of the following criteria:\n\n1. Patient must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.\n2. Female or male patients ≥ 18 years of age at the time of signing ICF.\n3. Pre- or perimenopausal women, who do not meet the criteria for post-menopausal status (defined in continuation) and men must be concurrently receiving a LHRH analogue for at least 28 days (if shorter, post-menopausal levels of serum estradiol\u002Ffollicle-stimulating hormone \\[FSH\\] must be confirmed analytically) prior to study randomization and are planning to continue LHRH agonist treatment during the study.\n\n   Post-menopausal women as defined by any of the following criteria:\n   1. Age ≥ 60 years;\n   2. Age \\\u003C 60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and\u002For FSH levels within the laboratory's reference range for post-menopausal females;\n   3. Documented bilateral surgical oophorectomy.\n4. Histologically- or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of either unresectable locally recurrent or metastatic disease confirmed by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.\n5. Documentation of ER\\[+\\] (≥10% positive stained cells) and HER2\\[-\\] (0-1+ by immunohistochemistry \\[IHC\\] or 2+ and negative by in situ hybridization \\[ISH\\] test) tumor according to the most recent American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guidelines as per local assessment. ER\\[+\\]\u002FHER2\\[-\\] status should be confirmed in metastatic setting, with exception of patients with bone and lung only disease.\n6. Patients with ESR1 mutational status will be determined before patient randomization using Guardant360 CDx (Guardant Health) test.\n\n   Note: Patients with previously determined ESR1 mutation using appropriately validated tests (Guardant360 CDx \\[Guardant Health\\], FoundationOne CDx, FoundationOne Liquid \\[Foundation Medicine Inc\\]) will be eligible for inclusion. This local determination can be performed either in blood or tumor samples.\n7. Radiological or objective evidence of disease progression on prior treatment with a CDK4\u002F6 inhibitor in combination with endocrine therapy for advanced disease after at least 6 months of treatment. Patients receiving CDK4\u002F6 inhibitor-based therapy in the adjuvant setting are also eligible provided that disease progression is confirmed after at least 12 months of treatment but no more than 12 months following CDK4\u002F6 inhibitor treatment completion in this scenario.\n8. Patients must have previously received at least one and no more than two lines of endocrine therapy for ABC. Progression during or within 12 months of adjuvant endocrine therapy is considered as a line of endocrine therapy for advanced disease.\n9. No prior elacestrant or other investigational SERDs, proteolysis targeting chimera (PROTAC), complete estrogen receptor antagonist (CERAN), or novel SERM, and\u002For PI3K\u002FAKT\u002FmTOR inhibitors, including everolimus, for advanced disease are permitted.\n\n   Note: Fulvestrant is permitted if treatment was completed administered at least 28 days before randomization.\n10. No prior chemotherapy for advanced disease is allowed.\n11. Evidence of measurable disease as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1), or non-measurable, but evaluable, disease, including bone-only disease with at least one lytic or mixed lytic-blastic bone lesion.\n12. Willingness and ability to provide the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue or block. If a newly obtained baseline biopsy of an accessible tumor lesion is not possible to be obtained prior randomization, an archival tissue sample will be accepted.\n13. Fasting serum cholesterol ≤ 300 mg\u002FdL or 7.75 mmol\u002FL and fasting triglycerides ≤ 2.5 times the upper limit of normal (x ULN).\n14. Adequate bone marrow and organ function:\n\n    1. Hematological (without platelet, red blood cell transfusion, and\u002For granulocyte colony-stimulating factor support within seven days before randomization): absolute neutrophil count (ANC) ≥ 1.5 x 109\u002FL; platelet count ≥ 100.0 x109\u002FL; and hemoglobin ≥ 9.0 g\u002FdL.\n    2. Hepatic: Serum albumin ≥ 2.5 g\u002FdL; total serum bilirubin \\\u003C 1.5 x ULN except for patients with Gilbert's syndrome who may be included if the total serum bilirubin is ≤ 3 x ULN or direct bilirubin ≤ 1.5 x ULN; alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 3 x ULN in patients with liver and\u002For bone metastases); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 x ULN (≤ 3 x ULN in patients with liver metastases).\n    3. Renal: Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL\u002Fmin as calculated by Cockcroft- Gault equation.\n    4. Coagulation: International normalized ratio (INR) ≤ 1.5 x ULN, unless that the patient meets the exception described in the exclusion criteria 16.\n15. Resolution of all acute toxic effects of prior anti-cancer therapy to grade ≤ 1 as determined by the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 (except for toxicities not considered a safety risk for the patient at Investigator's discretion).\n\n    Note: Patients with grade 2 alopecia are allowed.\n16. Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 7 days before randomization. In addition, they agree to use one highly effective method of birth control 28 days prior to start of treatment until 120 days after the last dose of study treatments. Female patients must refrain from egg cell donation and breastfeeding during this same time period.\n17. Male participants with a female partner of childbearing potential must be surgically sterile or using a highly effective method of contraception 28 days prior to treatment until 120 days after the last dose of study treatments to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period. Not engaging in heterosexual activity (sexual abstinence) for the duration of the study and 120 days after the last dose of study treatments is an acceptable practice if this is the preferred usual lifestyle of the participant.\n18. ECOG performance status of 0-1.\n19. Minimum life expectancy of ≥ 12 weeks at screening.\n\nExclusion Criteria:\n\nAny patient meeting ANY of the following criteria will be excluded from the study:\n\n1. Inability to comply with study and follow-up procedures.\n2. Formal contraindication to endocrine therapy defined as visceral crisis and\u002For rapidly or symptomatic progressive visceral disease.\n3. Current participation in another therapeutic clinical trial.\n4. Treatment with approved or investigational cancer therapy within 14 days prior to randomization except for fulvestrant that must be administered completed at least 28 days before randomization.\n5. Known active uncontrolled or symptomatic central nervous system (CNS) metastases and\u002For leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and\u002For progressive growth. Patients with a history of CNS metastases are eligible if they have been previously treated with local therapy, are clinically stable, and off anticonvulsants and steroids for at least 14 days before randomization.\n6. Intact uterus with a history of endometrial intraepithelial neoplasia (atypical endometrial hyperplasia or higher-grade lesion).\n7. Concurrent malignancy or malignancy within three years before randomization with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required.\n8. Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) or their incorporated substances.\n9. History of malabsorption syndrome or other condition that would interfere with enteral absorption (ongoing gastrointestinal obstruction\u002Fmotility disorder, malabsorption syndrome, or prior gastric bypass) or results in the inability or unwillingness to swallow pills.\n10. Palliative radiotherapy with a limited field of radiation within two weeks or with wide field of radiation or to more than 30% of the bone marrow within four weeks prior to randomization.\n11. Major surgical procedure or significant traumatic injury within 14 days before randomization or anticipation of need for major surgery within the course of the study treatment.\n12. Clinically relevant cardiovascular\u002Fcerebrovascular disease and\u002For cardiac dysfunction or conduction abnormalities including, but not confined, to any of the following:\n\n    a. Symptomatic pericarditis, unstable angina pectoris, documented myocardial infarction, coronary\u002Fperipheral artery bypass graft, symptomatic cardiac heart failure (CHF) (New York Heart Association \\[NYHA\\] Class II-IV), or cerebrovascular accident including transient ischemic attack within six months before study randomization.\n13. Concurrent uncontrolled atrial fibrillation, other ongoing cardiac dysrhythmias grade ≥ 2 as determined by NCI-CTCAE v.5.0, or prolonged QT Interval Corrected by Fridericia's formula (\\[QTcF\\] \\> 480 msec).\n14. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited, to any of the following:\n\n    1. Massive lung metastatic involvement (e.g., pleural effusion, lymphangitic carcinomatosis, etc.).\n    2. Any underlying pulmonary disorder (e.g., severe asthma, severe chronic obstructive pulmonary disease \\[COPD\\], restrictive lung disease, post Coronavirus disease (COVID-19) pulmonary fibrosis, etc.).\n    3. Any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.).\n    4. Prior pneumonectomy.\n15. History of non-infectious interstitial lung disease (ILD)\u002Fpneumonitis that required steroids, has current ILD\u002Fpneumonitis, or has suspected ILD\u002Fpneumonitis that cannot be ruled out by imaging at screening.\n16. Coagulopathy or any history of coagulopathy within six months before study enrollment, including history of deep vein thrombosis or pulmonary embolism. However, patients with the following conditions will be allowed to participate:\n\n    1. Adequately treated catheter-related venous thrombosis occurring more than 28 days prior to randomization.\n    2. Treatment with an anticoagulant (e.g., warfarin or heparin) for a thrombotic event occurring more than six months before randomization, or for an otherwise stable and allowed medical condition (e.g., well controlled atrial fibrillation), provided dose and coagulation parameters (as defined by local standard of care) are stable for at least 28 days prior to randomization.\n17. Concomitant treatment with immunosuppressive agents or chronic corticosteroids use before randomization with the following exceptions: topical applications, inhaled sprays, eye drops, mouthwash, or local injections are allowed. Patients on stable low dose of corticosteroids ( ≤ 10 mg\u002Fday of prednisone or equivalent) for at least two weeks before randomization are also permitted.\n18. Unable or unwilling to avoid prescription medications, over-the-counter medications, dietary\u002Fherbal supplements (e.g., St. John's wort), and\u002For foods (e.g., grapefruit, pomelos, star fruit, Seville oranges and their juices) that are moderate\u002Fstrong inhibitors or inducers of CYP3A4 activity. Participation will be allowed if the medication, supplements, and\u002For foods are discontinued for at least five half-lives or 14 days (whichever is shorter) prior to randomization and for the duration of the study.\n19. Pregnant or lactating women or patients not willing to apply highly effective contraception as defined in the protocol.\n20. Current known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antibody \\[HBsAg\\] test and a positive hepatitis B core antibody \\[HBcAb\\] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. Any other active uncontrolled infection at the time of screening is not allowed.\n21. Known substance abuse or any other concurrent severe and\u002For uncontrolled psychiatric or medical condition that would, in the Investigator's judgment, contraindicate patient participation.",{"count":184,"type":21},240,[186],"PHASE3","This trial will study a type of advanced breast cancer (ABC) defined as endocrine receptor (ER)-positive\u002Fhuman epidermal growth factor receptor 2(HER2)-negative and estrogen receptor 1 (ESR1)-mutated. Patients will be treated with elacestrant, a compound that acts as a selective estrogen receptor degrader, and everolimus (or placebo), a kinase inhibitor indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer.\n\nThe main purpose of the study is to analyze the efficacy (to find out how effective a treatment is) of elacestrant plus everolimus therapy in patients who have ER-positive\u002FHER2-negative, ESR1-mutated, ABC progressing to endocrine therapy and cyclin-dependent kinase 4\u002F6 (CDK4\u002F6) inhibitor. The efficacy of elacestrant plus everolimus combination will be determined by assessing the period from elacestrant plus everolimus (or placebo) treatment initiation until to the first occurrence of disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason, whichever occurs first, defined as progression free survival.\n\nRigorous eligibility criteria based on specific co-morbidities and clinicopathologic features of their disease have been designed to minimize the risk of patients participating in this study. The anticipated favorable clinical benefits of elacestrant combined with everolimus are projected to outweigh the risks of this treatment. This study will be performed in full compliance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and all applicable local Good Clinical Practice (GCP) and regulations.",[27,189,190,191],"ER-positive Breast Cancer","HER2-negative Breast Cancer","ESR1 Gene Mutation",[193,194,195,196,197],"ER-positive","HER22-negative","ESR1-mutation","CDK4\u002F6-inhibitor","Selective endocrine receptor degrader (SERD)","2026-03-30",{"date":200,"type":34},"2026-04-03",{"date":202,"type":34},"2024-12-05",{"date":204,"type":21},"2028-04",{"name":40,"class":41},99,{"id":208,"slug":209,"hasResults":11,"nctId":210,"briefTitle":211,"officialTitle":211,"acronym":212,"eligibilityCriteria":213,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":214,"targetDuration":4,"studyType":22,"phases":216,"briefSummary":217,"conditions":218,"keywords":220,"overallStatus":63,"whyStopped":4,"lastUpdateSubmitDate":222,"lastUpdatePostDateStruct":223,"startDateStruct":225,"completionDateStruct":226,"leadSponsor":228,"locationsCount":4},"100628388","phase-1-a-phase-ibii-study-to-evaluate-safety-and-efficacy-of-bexmarilimab-in-combination-with-doxorubicin-in-metastatic-soft-tissue-sarcoma-100628388","NCT07460986","A PHASE IB\u002FII STUDY TO EVALUATE SAFETY AND EFFICACY OF BEXMARILIMAB IN COMBINATION WITH DOXORUBICIN IN METASTATIC SOFT-TISSUE SARCOMA","BEXAR","Inclusion Criteria:\n\n1. Participant, or legal representative (if applicable), must be capable to understand the purpose of the Study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.\n2. Female or male participants ≥ 18 years of age at the time of signing ICF.\n3. For phase Ib (dose escalation):\n\n   * Histologically documented metastatic STS with no more than 3 lines of treatment.\n   * Participant has not received doxorubicin, but doxorubicin could be indicated for metastatic disease as per institutional guidelines.\n\n   For phase Ib (dose expansion) and for phase II:\n\n   • Metastatic STS with any of the following histologies: undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), dedifferentiated liposarcoma (DDLPS), myxoid liposarcoma (MLPS), leiomiosarcoma (LMS) with no prior treatment in the advanced setting. Capped to 33% of participants with UPS\u002FMFS, 33% of participants with DDLPS\u002FMLPS, and 33% of participants with LMS.\n4. Measurable disease according to RECIST v.1.1.\n5. Participant has adequate bone marrow, liver, and renal function:\n\n   * Hematological (without platelet, red blood cell transfusion, and\u002For granulocyte colony-stimulating factor support within 7 days before first Study treatment dose): Absolute neutrophil count (ANC) ≥ 1,000\u002Fmm3, platelet count ≥ 100 × 109\u002FL, and hemoglobin ≥ 9.0 g\u002FdL.\n   * Hepatic: Serum albumin ≥ 2.5 g\u002FdL; total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 3 ×ULN if Gilbert's syndrome); alkaline phosphatase (ALP) ≤ 2.5 ×ULN; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 ×ULN in participants with no liver metastasis and 5.0 ×ULN in participants with liver metastasis; partial thromboplastin \\[PT\\]-INR\u002Factivated partial thromboplastin time \\[PTT\\] \\\u003C1.5×ULN (≤ 2.0×ULN for participants on anticoagulation prophylactic regimen).\n   * Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 40 mL\u002Fmin\u002F1.73 m2 based on Cockcroft-Gault glomerular filtration rate estimation for participants with creatinine levels above institutional normal.\n6. Resolution of all acute toxic effects of prior anti-cancer therapy to grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 6.0 (v.6.0) (except for alopecia or other toxicities not considered a safety risk for the participant at investigator's discretion).\n7. Participants must be able to provide blood samples for PK analysis (for phase Ib), and blood samples and the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks at the time of the inclusion for translational studies (for phase Ib and phase II). Archival tissue sample should have preferably be taken ≤ 24 months before screening. If archival tissue is not available, a newly obtained baseline biopsy of an accessible tumor lesion is required prior to start of Study treatment.\n8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n9. Minimum life expectancy of ≥ 12 weeks at screening.\n10. Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 14 days before Study treatment initiation. In addition, they must agree to use one highly effective method of birth control from the time of screening until 7 months after the last dose of Study treatments. Female participants must refrain from egg cell donation and breastfeeding during this same period.\n11. Male participants who are sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of screening until 4 months after the last administration of the Study drug. Male participants must not donate or bank sperm during this same period.\n12. Participant must be accessible for treatment and follow-up.\n\nExclusion Criteria:\n\n1. Participation in another clinical trial, interventional or observational, until the Study's safety visit. Note: participation in retrospective studies or data analysis is allowed.\n2. Treatment with approved or investigational cancer therapy within 14 days prior to initiation of Study drug.\n3. Prior treatment with anthracyclines for localized or advanced disease.\n4. Prior treatment with immunocheckpoint inhibitors for localized or advanced disease.\n5. For phase Ib (dose expansion) and phase II: participant has received prior treatment in the advanced setting.\n6. Known active uncontrolled or symptomatic central nervous system (CNS) metastases and\u002For leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and\u002For progressive growth. Participants with a history of a CNS metastasis previously treated with curative intent (for example, stereotactic radiation or surgery) that have not progressed on follow-up imaging, have been asymptomatic for at least 60 days and are not receiving systemic corticosteroids and or\u002Fanticonvulsants, are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before randomization to rule out brain metastasis.\n7. Participants diagnosed with bone sarcomas, locally-aggressive sarcomas, GIST or Kaposi sarcoma.\n8. Have a concurrent malignancy or malignancy within 5 years of Study enrollment with the exception of carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.\n9. Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) or their incorporated substances.\n10. Major surgical procedure or significant traumatic injury within 14 days before the first dose of Study treatment or anticipation of need for major surgery within the course of the Study treatment.\n11. The patient requires systemic corticosteroid (≥10 mg\u002Fday prednisone or equivalent) or other immunosuppressive treatment. Topical, nasal, inhaled, and ophthalmic corticosteroids are allowed.\n12. Has an active cardiac disease or a history of cardiac dysfunction or conduction abnormalities including, but not confined, to any of the following:\n\n    * History and\u002For signs of active coronary artery disease\u002Fischemia with or without angina pectoris, documented myocardial infarction, or symptomatic congestive heart failure (CHF) (New York Heart Association \\[NYHA\\] Class II-IV) within six months prior to Study entry.\n    * Symptomatic pericarditis.\n    * Left ventricular ejection fraction (LVEF) \\\u003C 50% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO).\n    * History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, or ventricular tachycardia), which is symptomatic or requires treatment (NCI-CTCAE grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers will be permitted to enroll.\n    * QT Interval Corrected by Fridericia's formula (QTcF) prolongation to \\> 470 ms based on average of the screening triplicate 12-lead ECG.\n    * Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.\n13. Participants with a history of chronic ulcers or clinically relevant liver disease leading to Child Pugh Score C or higher. If the history of abnormal liver function is related to previous hematologic malignancy or it's treatment, the participant may be enrolled after discussing with the Medical Monitor.\n14. Pregnant or lactating women or participants not willing to apply highly effective contraception as defined in the protocol.\n15. Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the Study.\n16. Current known infection with hepatitis B virus (HBV), or hepatitis C virus (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 (PCR) is negative for HCV RNA.\n17. Has active primary immunodeficiency, known human immunodeficiency virus (HIV) infection with positive viral load. Note: HIV-infected participants on effective anti-retroviral therapy with undetectable viral load are eligible for inclusion, provided their therapy does not include CYP3A4 inhibitors or inducers (such as nevirapine or atazanavir).\n18. Other active uncontrolled infection at the time of enrollment.\n19. Receipt of live or attenuated vaccine within 30 days prior to the first dose of Study treatment.\n20. A history of uncontrolled seizures, central nervous system (CNS) disorders, or serious and\u002For unstable pre-existing psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to Study drugs or interfering with participant safety.\n21. Known substance abuse or any other concurrent severe and\u002For uncontrolled medical condition that would, in the investigator's judgment, contraindicate participant participation.\n22. Inability or unwillingness to comply with the requirements of the protocol in the opinion of the investigator.",{"count":215,"type":21},278,[105,24],"This trial will Study a type of sarcoma defined metastatic soft-tissue sarcoma (STS). Participants will be treated with bexmarilimab, a CLEVER-1 antibody plus doxorubicin, a chemotherapy. The main purpose of the Study is to analyze the safety (to find out how safe or toxic a treatment is to appropriately manage the risks) and efficacy (to find out how effective a treatment is) of bexmarilimab combined with doxorubicin in participants who have STS.",[219],"Sarcoma of Soft Tissue",[221],"Soft Tissue Sarcoma, Clever-1, Bexmarilimab","2026-03-05",{"date":224,"type":34},"2026-03-10",{"date":171,"type":21},{"date":227,"type":21},"2028-10",{"name":40,"class":41},{"id":230,"slug":231,"hasResults":11,"nctId":232,"briefTitle":233,"officialTitle":234,"acronym":235,"eligibilityCriteria":236,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":237,"targetDuration":4,"studyType":22,"phases":239,"briefSummary":240,"conditions":241,"keywords":242,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":248,"lastUpdatePostDateStruct":249,"startDateStruct":250,"completionDateStruct":252,"leadSponsor":254,"locationsCount":255},"100493675","phase-2-a-poc-study-to-evaluate-treatments-efficacy-by-monitoring-mrd-using-ctdna-in-hr-positiveher2-negative-ebc-population-100493675","NCT05708235","A PoC Study to Evaluate Treatments' Efficacy by Monitoring MRD Using ctDNA in HR-positive\u002FHER2-negative EBC Population","A Proof of Concept Study to Evaluate Treatments' Efficacy by Monitoring Minimal Residual Disease Using ctDNA in HR-positive\u002FHER2-negative Early Breast Cancer Population","MiRaDoR","Eligibility criteria for the surveillance phase:\n\nNote: Patients who have not participated in the surveillance phase but have a positive ctDNA test (conducted under other circumstances) will be allowed to enter directly into the treatment phase after confirmation of ctDNA positivity by the study test. Therefore, these patients will not need to meet all the inclusion criteria for the surveillance phase but will need to meet all the inclusion criteria for the treatment phase.\n\nInclusion criteria for surveillance phase:\n\n1. Signed informed consent form (ICF) prior to participation in any Studyrelated activities.\n2. Male or female patients aged 18 years or older.\n3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.\n4. Histologically proven primary HR-positive according to the updated American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) 2020 guidelines and HER2-negative BC as per ASCO\u002FCAP 2018 criteria based on local testing on the most recent analyzed biopsy.\n5. Patients with high-risk early-stage BC according to at least one of the following criteria: a. If there is no previous neoadjuvant chemotherapy: i. pN2-N3 or ii. pN1 (including micrometastasis - pN1mi) if:\n\n1\\. pT3-T4, or 2. pT2 and high genomic risk and\u002For histological grade III and\u002For Ki 67≥30%. b. If patients have received previous neoadjuvant chemotherapy, they must have had residual invasive disease defined as at least one of the following: i. Residual invasive disease in lymph nodes (ypN+, including ypN1mi) ii. ypN0 with residual invasive disease in breast if:\n\n1. cT3-4, or\n2. cT2 and high genomic risk and \u002F or histological grade III and \u002F or Ki67≥30%. Note: Genomic risk using platforms such as Oncotype Dx, Prosigna or Mammaprint won't be assessed for the screening to participate in the Study. However, patients with the detailed scores assessed prior to Study inclusion, may be eligible.\n\n6\\. On adjuvant treatment with ET for at least two years and no more than seven years at the time of Study enrolment with an additional three years of ET planned, and at least 6 months prior to enrolment on the same ET treatment with AI or tamoxifen (LHRH is mandatory for men and premenopausal women receiving AI, as well as for premenopausal women treated with tamoxifen, except in cases of bilateral oophorectomy.) Note: Pre-menopausal patients treated with tamoxifen alone are excluded.\n\n7\\. Prior treatment with cyclin-dependent kinases 4\u002F6 (CDK4\u002F6) inhibitors will be allowed in the case of an interval of at least 12 months between the last dose and inclusion in the trial.\n\n8\\. No prior treatment with SERDs will be allowed.\n\n9\\. Willingness and ability to provide tissue from one archival tumor tissue sample (either from diagnostic biopsy, primary surgery, or where available from a residual disease post-neoadjuvant therapy).\n\nNote: Patients with multifocal BC may be enrolled, if archival tissue samples from at least two tumors are available and after histopathological examination, all tumors meet pathologic criteria for HR-positive and HER2-negative BC.\n\n10\\. Absence of metastatic disease by routine clinical assessment (computed tomography \\[CT\\] scan of the thorax and abdomen, and bone scan or positron emission tomography \\[PET\\] scan). confirmed no longer than three months prior to Study inclusion.\n\n11\\. Patients must have had surgery for their primary BC with documented clear margins (as per local guidelines) and they must have received radiotherapy if indicated (as per local guidelines).\n\n12\\. Patients must be able and willing to adhere to Study procedures.\n\nExclusion criteria for surveillance phase:\n\n1. Patients with pathological complete response (pCR) after neoadjuvant treatment.\n2. Any concurrent or planned treatment for the current diagnosis of BC other than adjuvant ET except for denosumab or zoledronic acid, which are allowed.\n3. Diagnosis of an alternative cancer in the five years prior to primary BC diagnosis other than for non-melanoma carcinoma of the skin or cervical carcinoma in situ. Other stage I tumors will be discussed case by case prior to inclusion with the Medical Monitor of the Study.\n4. Active or prior documented inflammatory bowel disease (i.e., Crohn's disease, ulcerative colitis, or a preexisting chronic condition resulting in baseline grade ≥1 diarrhea) that may significantly alter the absorption of oral drugs.\n5. Active cardiac disease or history of cardiac dysfunction including any of the following:\n\n   1. History (within two years from screening) or presence of idiopathic bradycardia or resting heart rate \\\u003C50 beats per minute at screening.\n   2. History of angina pectoris or symptomatic coronary heart disease within 12 months prior to Study entry.\n   3. QT interval corrected through use of Fridericia's formula (QTcF) \\> 450 ms for women and \\> 470 ms for men by at least three electrocardiograms (ECGs) \\> 30 minutes apart.\n   4. History or presence of an abnormal ECG that is clinically significant in the investigator's opinion,\n   5. History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy cardiomyopathy, infiltrative cardiomyopathy, moderate-to-severe valve disease), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of long QT syndrome within 12 months.\n6. History of pneumonitis, interstitial lung disease (ILD), or pulmonary fibrosis.\n7. Known history of Human Immunodeficiency Virus (HIV) infection (testing not required as part of Study screening).\n8. Clinically significant liver disease consistent with Child-Pugh C, including active hepatitis (e.g., hepatitis B virus \\[HBV\\] or hepatitis C virus \\[HCV\\]), current alcohol abuse, cirrhosis, or positive test for viral hepatitis\n9. Active bleeding diathesis venous thrombo-embolism, previous history of bleeding diathesis, or chronic anti-coagulation treatment, or any indications or history of Disseminated Intravascular Coagulation (DIC) or Deep vein thrombosis (DVT). Low molecular weight heparin (LMWH), low dose aspirin or clopidogrel are permitted.\n10. Creatinine clearance \\\u003C 30mL\u002Fmin.\n11. Participants with renal dysfunction who require dialysis.\n12. Patient who has any other concurrent severe and\u002For uncontrolled medical condition that would, in the Investigator' opinion cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol.\n13. Females who are known to be breastfeeding or pregnant as determined by a serum pregnancy test, Human chorionic gonadotropin (β-HCG), prior to the administration of any trial treatment (once during the treatment phase). Since β-HCG over expression can also be elevated in some tumor types, a positive result should be confirmed with a validated alternative test (e.g., ultrasound).\n14. Female or male participants planning a pregnancy.\n\nEligibility criteria for the treatment phase:\n\nPatients will be considered eligible to enter to the treatment phase and to be allocated to standard ET only followed by change in treatment after a 90-day period , giredestrant monotherapy, giredestrant plus abemaciclib, or giredestrant plus inavolisib if they fulfill all the inclusion and none of the exclusion criteria listed below.\n\nInclusion criteria for treatment phase:\n\n1. Signed treatment ICF prior to Study inclusion.\n2. Male or female patients aged 18 years or older.\n3. ctDNA positivity with no evidence of clinical or radiologic recurrence by standard assessments (e.g.: breast ultrasound, staging scans, RMN).\n4. ECOG performance status 0 or 1.\n5. Patients must have received the same ET during at least the last 6 months. A temporary discontinuation of \\\u003C 90 days during the surveillance phase is allowed.\n6. Receiving LHRH agonist therapy alongside the same ET treatment for at least 90 days prior to initiation of one of the available Study treatments if male or pre-menopausal.\n7. Prior treatment with cyclin-dependent kinases 4\u002F6 (CDK4\u002F6) inhibitors will be allowed in the case of an interval of at least 12 months between the last dose and inclusion in the trial.\n8. No prior treatment with SERDs will be allowed.\n9. Absence of metastatic disease by routine clinical assessment (computed tomography \\[CT\\] scan of the thorax and abdomen, and bone scan or positron emission tomography \\[PET\\] scan). confirmed no longer than three months prior to Study inclusion.\n10. Patients must have had surgery for their primary BC with documented clear margins (as per local guidelines) ) and they must have received radiotherapy if indicated (as per local guidelines).\n11. Willingness and ability to provide tissue from one archival tumor tissue sample (either from diagnostic biopsy, primary surgery, or where available from a residual disease post-neoadjuvant therapy).\n12. Female of reproductive potential and male patients with female partners of childbearing potential, must remain abstinent and truly abstain from sexual activity (refrains from heterosexual intercourse) or use locallyrecognized adequate methods of contraception (described as that with a failure rate \\\u003C1%) for the duration of trial treatment. In addition, patients must follow these guidelines for a certain period of time after the last dose of trial treatment, specified in the protocol depending on which treatment arm the patient is allocated in. During this indicated period of time, female and male patients must as well refrain from donating eggs or sperm.\n\n    Note: Female patients will be deemed not of childbearing potential if they are post-menopausal or have had irreversible sterilization. Well-defined pre-menopausal status refers to women who have not reached the postmenopausal state because they are not permanently infertile due to prior bilateral oophorectomy, age ≥60 years or age \\\u003C60 years with amenorrhea for ≥12 months and estradiol and follicle-stimulating hormone (FSH) levels in the post-menopausal range.\n13. Resolution of all acute toxic effects of prior anti-cancer therapy to Grade ≤1 as determined by the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v) 5.0 (except for alopecia, or other toxicities not considered a safety risk for the patient at investigator's discretion). Adverse events (AEs) of current ET treatment are not included.\n14. Adequate hematologic and organ function within 14 days before the first Study treatment on Day 1 of Cycle 1, defined by the following:\n\n    * Hematological (without platelet, red blood cell (RBC) transfusion, and\u002For granulocyte colony-stimulating factor support within 7 days before first Study treatment dose): White blood cell (WBC) count \\> 3.0 x 109\u002FL, absolute neutrophil count (ANC) ≥ 1.5 x 109\u002FL, platelet count ≥ 100.0 x109\u002FL, and hemoglobin ≥ 9.0 g\u002FdL (≥ 5.6 mmol\u002FL).\n    * Hepatic: Serum albumin ≥ 3 g\u002FdL; Bilirubin ≤ 1.5 times the upper limit of normal (ULN) (≤ 3 x ULN in the case of Gilbert's disease); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN; alkaline phosphatase (ALP) ≤ 2 × ULN.\n    * Renal: serum creatinine level ≤ 1.5 × the upper limit of normal (ULN) or an estimated glomerular filtration rate (eGFR) ≥ 30 mL\u002Fmin\u002F1.73 m², as calculated using the 2021 CKD-EPI creatinine equation (National Kidney Foundation, 2021).\n\n    Note: eGFR should be determined using the following standardized CKDEPI 2021 formula (without race adjustment): eGFR (mL\u002Fmin\u002F1.73 m²) = 142 × min(Scr\u002Fκ, 1)\\^α × max(Scr\u002Fκ, 1)\\^-1.200 × 0.9938\\^Age × 1.012 \\[if female\\]. Scr = serum creatinine in mg\u002FdL, κ = 0.7 for females; 0.9 for male; α = - 0.241 for females; -0.302 for males; min(Scr\u002Fκ, 1) = the lesser of Scr\u002Fκ or 1; max(Scr\u002Fκ, 1) = the greater of Scr\u002Fκ or 1; Age = age in years; The multiplication factor 1.012 is applied only for females.\n15. Participants who are able and willing to swallow, retain, and absorb oral medication.\n16. Patients must be able and willing to adhere to Study procedures.\n\nAdditional inclusion criteria for Arm C (giredestrant + abemaciclib arm):\n\n1\\. Patients with prior diagnosis of thrombosis might be included as long as they are under stable anti-coagulation regimen therapy 28 days prior to starting treatment with abemaciclib.\n\nAdditional inclusion criteria for Arm D (giredestrant + inavolisib arm):\n\n1. Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test: Qiagen therascreen PIK3CA RGQ PCR PCR kit - CE-IVD). This determination will be done in tumor tissue.\n2. No prior treatment with any phosphatidylinositol 3-kinase (PI3K), Akt, or mammalian target of rapamycin (mTOR) inhibitors, or any agent whose mechanism of action is to inhibit the PI3K\u002FAkt\u002FmTOR pathway.\n\nExclusion criteria for treatment phase:\n\n1. Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances.\n2. Undergoing any other simultaneous anti-cancer treatment since enrolling in the Study, other than hormonal therapy or a bisphosphonate (or denosumab).\n3. Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 28 days of start of Study drug, or patients who have not recovered from the side effects of any major surgery.\n4. Treatment with strong Cytochrome P450 3A4 (CYP3A4) inhibitors or strong CYP3A4 inducers within 14 days or five drug-elimination halflives, whichever is longer, prior to initiation of one of the available Study treatments.\n5. Patient has a history of non-compliance to medical regimen.\n\nAdditional exclusion criteria for Arm D (giredestrant + inavolisib arm):\n\n1. Type 2 diabetes requiring ongoing systemic treatment at the time of Study entry; or any history of Type 1 diabetes.\n2. Fasting glucose ≥126 mg\u002FdL or ≥7.0 mmol\u002FL and hemoglobin A1C (HbA1c) ≥ 6.0%.\n3. Any concurrent ocular or intraocular condition excluding cataracts (e.g., diabetic retinopathy) that, in the opinion of the investigator, would require medical or surgical intervention during the Study period to prevent or treat vision loss that might result from that condition.\n4. Active inflammatory (e.g., uveitis or vitritis) or severe infectious conditions (e.g., keratitis, scleritis, or endophtalmitis) in either eye or history of idiopathic or autoimmune-associated uveitis in either eye.\n5. Inability to confirm biomarker eligibility based on valid results from either central testing of blood or local testing of blood or tumor tissue that documents one of the protocol-defined PIK3CA mutations.",{"count":238,"type":21},976,[24],"This trial is a multicenter, open-label, non-comparative, phase II, biomarker-driven adjuvant treatment study involving the periodic collection and analysis of blood samples from patients with HR-positive\u002FHER2-negative early-stage BC at higher risk of relapse, who have undergone surgery within the previous five years, with no evidence of locoregional, contralateral, or distant disease.\n\nThe study design is composed by an initial pre-screening phase, a molecular follow-up phase (ctDNA surveillance phase), and an interventional therapeutic phase (treatment phase).\n\nAfter informed consent is obtained, a total of 976 eligible patients will enter a ctDNA surveillance in which primary tumor tissue and matched normal blood will be collected from each patient to obtain a patient-specific somatic mutations panel (tumor signature).\n\nAt the event of ctDNA positivity, patients will be screened to enter the treatment phase of the study. Upon confirmed eligibility, a total of 40 patients will be allocated in one of the following trial's arms adopting a sequential recruitment strategy:\n\nArm A: Control Arm (N=10) Arm B: Experimental Arm with giredestrant (N=10) Arm C: Experimental Arm with giredestrant + abemaciclib (N=10) Arm D: Experimental Arm with giredestrant + inavolisib (N=10)\n\nIf the strategy of ctDNA monitoring enables physicians to identify patients at high risk of relapse and assess whether treatment at molecular relapse can improve outcome, new cohorts may be added to the study.",[85],[243,244,245,246,247],"ctDNA","Early breast cancer","HR-positive\u002FHER2-negative","MRD","Minimal Residual Disease","2026-03-02",{"date":222,"type":34},{"date":251,"type":34},"2024-04-01",{"date":253,"type":21},"2028-06-30",{"name":40,"class":41},41,{"id":257,"slug":258,"hasResults":11,"nctId":259,"briefTitle":260,"officialTitle":261,"acronym":262,"eligibilityCriteria":263,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":264,"targetDuration":4,"studyType":22,"phases":266,"briefSummary":267,"conditions":268,"keywords":272,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":277,"lastUpdatePostDateStruct":278,"startDateStruct":280,"completionDateStruct":282,"leadSponsor":283,"locationsCount":93},"100540297","phase-2-repotrectinib-in-ros1-positive-non-small-cell-lung-cancer-patients-with-active-brain-metastasis-100540297","NCT06315010","REPotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain mEtastasis","A Phase II Study Assessing Safety and Efficacy of REPotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain mEtastasis (REPOSE Study)","REPOSE","Inclusion Criteria:\n\nPatients will be included in the study only if they meet all the following criteria:\n\n1. Patient must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.\n2. Female or male patients ≥ 18 years of age at the time of signing ICF.\n3. Patients must be capable to swallow capsules intact (without chewing, crushing, or opening).\n4. Histologically documented NSCLC.\n5. Patients may have active brain metastases with or without related symptoms.\n6. No indication for immediate local therapy (neurosurgery, brain radiotherapy) of brain metastases per local investigator.\n\n   Note: in case of immediate local therapy is needed, the study's medical monitor should be consulted.\n7. Type II leptomeningeal disease per European Association of Neuro-Oncology (EANO) - European Society for Medical Oncology (ESMO) Clinical Practice Guidelines are allowed.\n8. Patients with confirmed ROS1 rearrangement. Prior to study enrollment, patients must have had confirmation of ROS1 rearrangement, which should have been determined locally by a certified laboratory using methods such as fluorescent in situ hybridization (FISH), next generation sequencing (NGS), quantitative PCR (qPCR), or immunohistochemistry (IHC).\n9. Measurable disease according to RANO-BM criteria, with at least one measurable brain lesion of ≥10 mm on T1-weighted, gadolinium-enhanced magnetic resonance imaging (MRI).\n10. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.\n11. Minimum life expectancy of ≥ 6 weeks at screening.\n12. No limit in number of prior chemotherapies, immunotherapy or other non-ROS1 TKI regimens. De novo patients can also be included.\n13. Patients must not have previously received any ROS1 TKI-based treatment.\n14. Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.\n15. If feasible, archival tumor biopsy sample at baseline (from primary tissue or any metastatic site) should be provided.\n16. Patient has adequate bone marrow, liver, and renal function:\n\n    I. Hematological (without platelet, red blood cell transfusion, and\u002For granulocyte colony-stimulating factor support within 28 days before first study treatment dose): White blood cell (WBC) count \\> 3.0 x 109\u002FL, absolute neutrophil count (ANC) ≥ 1.5 x 109\u002FL, platelet count ≥ 100.0 x109\u002FL, and hemoglobin ≥ 8.0 g\u002FdL (≥ 4.96 mmol\u002FL).\n\n    II. Hepatic: Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 3 in patients with liver metastases or know history of Gilbert's disease); alkaline phosphatase (ALP) ≤ 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 times ULN (≤ 5 in patients with liver metastases); international normalized ratio (INR) \\\u003C 1.5.\n\n    III. Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 40 mL\u002Fmin\u002F1.73 m2 based on Cockcroft-Gault glomerular filtration rate estimation for patients with creatinine levels above institutional normal.\n17. Resolution of all acute toxic effects of prior anti-cancer therapy to grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v.5.0) (except for alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).\n18. Women of childbearing potential (WOCBP) who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 14 days before study treatment initiation. In addition, they must agree to use one highly effective method of birth control from the time of screening until 2 months after the last dose of study treatments. Female patients must refrain from egg cell donation and breastfeeding during this same period.\n\n    Note: Due to a potential loss of effectiveness of hormonal contraceptives caused by interaction with study intervention, if WOCBP use hormonal contraceptives (including oral hormonal contraceptives), they must use either another form of non-hormonal highly effective contraception or a reliable barrier method.\n19. Male participants who are sexually active with a WOCBP partner must be surgically sterile or using an acceptable method of contraception from the time of screening until 4 months after the last administration of the study drug. Male participants must not donate or bank sperm during this same period.\n20. Patient must be accessible for treatment and follow-up.\n\nExclusion Criteria:\n\nAny patient meeting ANY of the following criteria will be excluded from the study:\n\n1. Major surgery within four weeks of the start of treatment.\n2. Type I leptomeningeal disease per ESMO-EANO guidelines.\n3. Have received prior radiotherapy within two weeks before the first dose of Study treatment (four weeks in case of radiation therapy of the central nervous system). Participants must have recovered from all radiation-related toxicities, not require steroids, and not have had radiation pneumonitis.\n4. Treatment with approved or investigational cancer therapy within14 days prior to initiation of Study treatment.\n5. Any of the following cardiac criteria:\n\n   I. Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \\> 470 msec obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value.\n\n   II. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \\> 250 msec).\n\n   III. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval.\n6. Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary\u002Fperipheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥ 2.\n7. Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).\n8. Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.\n9. Peripheral neuropathy grade ≥ 2.\n10. History of extensive, disseminated, bilateral, or presence of NCI CTCAE grade 3 or 4 interstitial fibrosis or interstitial lung disease (ILD) including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, ILD, obliterative bronchiolitis, and pulmonary fibrosis. Patients with a history of prior radiation pneumonitis are not excluded.\n11. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study or could compromise the protocol objectives in the opinion of the Investigator.\n12. Presence or history of any other primary malignancy other than NSCLC within 5 years prior to enrollment into the study.\n\n    Note: Patients with a history of adequately treated basal or squamous cell carcinoma of the skin or any adequately treated in situ carcinoma may be included in the study.\n13. Current use or anticipated need for drugs that are known to be strong Cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or inducers.\n\n    Note: midazolam requires diligent monitoring in situations where there is an unprecedented necessity for co-administration. These cases should be discussed with the study's medical monitor.\n14. Patients requiring concomitant use of chronic systemic (intravenously \\[IV\\] or oral) corticosteroids at doses higher than 8 mg dexamethasone per day or other immunosuppressive medications except for managing adverse events (AEs); (inhaled steroids or intra articular steroid injections are permitted in this study).\n\n    Note: The use of stable corticosteroid therapy in patients with brain metastases should be discussed with the Sponsor's Medical Monitor.\n15. Hypersensitivity to the Study drug or any of its ingredients.\n16. Prior exposure to other investigational medical products within five times the half-life of the drug\u002Fmetabolites before the Screening Visit.\n17. Contraindications to MRI, including but not limited to claustrophobia.",{"count":265,"type":21},20,[24],"REPOSE is a phase II clinical trial exploring the safety and efficacy of repotrectinib in patients with non-small cell lung cancer (NSCLC) characterized by the presence of brain metastasis (BM) and whose tumors have mutated ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) gene.",[269,270,271],"NSCLC","Brain Metastases","ROS1 Gene Rearrangement",[273,274,275,276],"Metastatic NSCLC","Brain metastasis","ROS1","Repotrectinib","2026-02-23",{"date":279,"type":34},"2026-02-25",{"date":281,"type":34},"2025-06-27",{"date":204,"type":21},{"name":40,"class":41},{"id":285,"slug":286,"hasResults":11,"nctId":287,"briefTitle":288,"officialTitle":289,"acronym":290,"eligibilityCriteria":291,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":292,"targetDuration":4,"studyType":22,"phases":293,"briefSummary":294,"conditions":295,"keywords":298,"overallStatus":63,"whyStopped":4,"lastUpdateSubmitDate":305,"lastUpdatePostDateStruct":306,"startDateStruct":308,"completionDateStruct":309,"leadSponsor":310,"locationsCount":4},"100621173","phase-2-study-of-sacituzumab-govitecan-with-atropine-to-improve-tolerability-in-advanced-tnbc-and-hrher2--breast-cancer-100621173","NCT07367178","Study of Sacituzumab Govitecan With Atropine to Improve Tolerability in Advanced TNBC and HR+\u002FHER2- Breast Cancer","Phase II Study to Improve Sacituzumab Govitecan Tolerance With Atropine in Patients With Advanced Triple-Negative and Hormone Receptor-Positive\u002FHER2-Negative Breast Cancer","SATROPIN","Inclusion Criteria:\n\n1. Participant, or legal representative (if applicable), must be capable of understanding the purpose of the Study and have signed a written informed consent form (ICF) prior to beginning specific protocol procedures.\n2. Female or male participants ≥ 18 years of age at the time of signing ICF.\n3. ECOG performance status of 0 or 1.\n4. Minimum life expectancy of ≥ 12 weeks at screening.\n5. Unresectable locally advanced or metastatic disease documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to curative therapy.\n6. For TNBC participants only:\n\n   i. Histologically confirmed TNBC of the most recent available sample per American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) 2018 criteria on the most recently analyzed biopsy. TNBC status is defined as \\\u003C1% expression for estrogen receptor (ER) and progesterone receptor (PgR) and negative for human epidermal growth factor receptor 2 (HER2) (0-1+ by immunohistochemistry \\[IHC\\] or 2+ and negative by in situ hybridization \\[ISH\\] test).\n7. For HR(+)\u002FHER2(-) breast cancer participants only:\n\n   i. Histologically confirmed HR(+)\u002FHER2(-) breast cancer of the most recent available sample per ASCO\u002FCAP 2018 criteria on the most recently analyzed biopsy. HR(+)\u002FHER2(-) status is defined as ≥1% expression for ER and\u002For PgR and negative for HER2 (0-1+ by IHC or 2+ and negative by ISH test).\n\n   ii. Disease progression to at least one prior endocrine therapy for advanced disease.\n\n   iii. Disease progression to previous CDK4\u002F6i-based therapy in any setting. For participants who received CDK4\u002F6i in the adjuvant setting, a minimum of one year of treatment and a disease-free interval (DFI) of ≤12 months are required.\n\n   Note: For participants with ER-low positive tumor (defined as ER expression between 1% and 10%) previous therapy with CDK4\u002F6 inhibitors and\u002For endocrine therapy is permitted but not required.\n8. Disease progression to no more than two prior standard of care chemotherapy-based regimens for advanced disease (prior ADC will count as a chemotherapy-based regimen).\n\n   Note: Earlier adjuvant or neoadjuvant therapy for early breast cancer will be considered as one of the required prior regimens if the development of unresectable locally advanced or metastatic disease occurred within a 12-month period after treatment completion.\n9. Prior treatment with a trophoblast cell-surface antigen 2 (TROP2) ADC and\u002For topoisomerase I inhibitor or an ADC containing a topoisomerase I inhibitor is only allowed in the (neo)adjuvant setting if the development of unresectable locally advanced or metastatic disease occurred at least 12 months after treatment completion.\n10. Measurable or non-measurable, but evaluable disease, as per RECIST v.1.1.\n11. Participants must have adequate bone marrow, liver, and renal function:\n\n    i. Adequate hematologic counts without transfusion or growth factor support within two weeks before of study drug initiation (hemoglobin ≥ 9 g\u002FdL, ANC ≥ 1500\u002Fmm3, and platelets ≥ 100,000\u002F μL).\n\n    ii. Adequate renal and hepatic function (creatinine clearance of ≥ 60 ml\u002Fmin, may be calculated using Cockcroft-Gault equation; bilirubin ≤ 1.5 x ULN and AST\u002FALT ≤ 3.0 x ULN or 5 x ULN if known liver metastases).\n\n    Note: Participants with a known or genetically confirmed Gilbert's syndrome (based on UGT1A1 polymorphism testing) may be enrolled provided that total bilirubin is \\\u003C1.5 × ULN. The diagnosis of Gilbert's syndrome must be recorded in the patient's medical history, and if UGT1A1 status is available, the type of mutation should also be documented.\n12. Participants must be willing to provide the most recent archival tumor tissue sample (from the primary breast tumor or a metastatic site) at baseline, as well as biological samples (blood and stool) at the established time points.\n13. Resolution of all acute toxic effects of prior anticancer therapy to grade ≤1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 6.0 (v.6.0) (except for alopecia or other toxicities not considered a safety risk for the participant at investigator's discretion).\n14. Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 14 days before Study treatment initiation. In addition, they must agree to use one highly effective method of birth control from the time of screening until six months after the last dose of Study treatment. Female participants must refrain from egg cell donation and breastfeeding during this same period.\n15. Male participants who are sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of screening until three months after the last administration of Study treatment. Male participants must not donate or bank sperm during this same period.\n16. Participants must be accessible for treatment and follow-up.\n\nExclusion Criteria:\n\n1. Participation in another clinical trial, interventional or observational, until the Study's safety visit.\n\n   Note: Participation in retrospective studies or data analysis is allowed.\n2. Known leptomeningeal disease or active uncontrolled or symptomatic central nervous system (CNS) metastases as indicated by clinical symptoms, and\u002For progressive growth are excluded.\n\n   Note: Participants with a history of CNS metastases are eligible if they have been previously treated with local therapy, are clinically stable, and off anticonvulsants and steroids for at least 14 days before the first dose of Study treatment.\n3. Have a concurrent malignancy or malignancy within three years of Study enrollment with the exception of carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.\n4. Known allergy or hypersensitivity reaction to any investigational medicinal product(s) (IMP\\[s\\]) or its (their) incorporated substances.\n5. Participants at risk of urinary retention (e.g.,those with prostatic hypertrophy), prior history of glaucoma, both open and closed angle, and previous diagnosis of myasthenia gravis, conditions in which atropine is contraindicated.\n6. Requirement for ongoing therapy with any prohibited medications listed in the protocol.\n7. Have received prior radiotherapy within two weeks before the first dose of Study treatment (four weeks in case of radiation therapy of the central nervous system). Participants must have recovered from all radiation-related toxicities, not require steroids.\n8. Major surgical procedure or significant traumatic injury within 14 days before the first dose of Study treatment or anticipation of need for major surgery within the course of the Study treatment.\n9. Known history of unstable angina, myocardial infarction, or cardiac heart failure present within six months of study initiation or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy or history of QT interval prolongation.\n10. Clinically significant active pulmonary compromise at screening (e.g., ongoing infection, uncontrolled COPD\u002Fasthma exacerbation).\n\n    Note: Participants with stable chronic lung diseases (e.g., controlled COPD, asthma, bronchiectasis, post-COVID fibrosis) may be enrolled but atropine should be used with caution and participants should be monitored for respiratory complications.\n11. Known history of clinically significant bleeding, thrombosis, intestinal obstruction, or gastrointestinal perforation within six months of study initiation.\n12. Documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or a preexisting chronic condition resulting in baseline grade ≥1 diarrhea).\n13. Any other serious medical condition and\u002For abnormality in clinical laboratory tests that, in the Investigator's judgment, precludes the participant's safe participation in and completion of the Study.\n14. Current known infection with hepatitis B virus (HBV), or hepatitis C virus (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 (PCR) is negative for HCV RNA.\n15. Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection.\n\n    i. Note: Participants with HIV on antiretroviral therapy (ART) with well-controlled HIV infection\u002Fdisease are allowed.\n\n    ii. Participants on ART must have a CD4+ T-cell count ≥ 350 cells\u002Fmm3 at time of screening.\n\n    iii. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies\u002FmL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening.\n\n    iv. Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to Study entry.\n\n    v. The combination of the ART regimen must not contain any medications that may interfere with SN-38 metabolism (such as CYP3A4 inhibitors or inducers as raltegravir, nevirapine, or atazanavir).\n16. Other active uncontrolled infection at the time of enrollment.\n17. Receipt of live or attenuated vaccine within 30 days prior to the first dose of Study treatment.\n18. Pregnant or lactating women or participants not willing to apply highly effective contraception as defined in the protocol.\n19. Treatment with approved or investigational cancer therapy within 14 days prior to initiation of Study treatment.",{"count":132,"type":21},[24],"The SATROPIN study is an international, multicenter, open-label, single-arm, phase II clinical trial to assess whether the use of prophylactic administration of atropine may prevent diarrhea in participants with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) or hormone receptor-positive\u002FHER2-negative (HR(+)\u002FHER2-) treated with sacituzumab govitecan.",[85,296,297],"Advanced HR+\u002FHER2- Breast Cancer","Advanced Triple-Negative Breast Cancer",[299,300,301,302,303,304,290],"Advanced TNBC","Sacituzumab govitecan","Atropine","Tolerance","Advanced HR+\u002FHER2-","Prophylaxis","2026-01-26",{"date":307,"type":34},"2026-01-28",{"date":171,"type":21},{"date":38,"type":21},{"name":40,"class":41},{"id":312,"slug":313,"hasResults":11,"nctId":314,"briefTitle":315,"officialTitle":316,"acronym":317,"eligibilityCriteria":318,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":319,"targetDuration":4,"studyType":22,"phases":321,"briefSummary":322,"conditions":323,"keywords":326,"overallStatus":63,"whyStopped":4,"lastUpdateSubmitDate":332,"lastUpdatePostDateStruct":333,"startDateStruct":335,"completionDateStruct":337,"leadSponsor":339,"locationsCount":4},"100606698","phase-2-platform-trial-assessing-uptake-safety-and-efficacy-of-theranostic-agents-in-solid-tumors-with-active-brain-metastases-100606698","NCT07178938","Platform Trial Assessing Uptake, Safety and Efficacy of Theranostic Agents in Solid Tumors With Active Brain Metastases","An International, Multicenter, Open-label, Multicohort, Platform Trial Assessing Uptake, Safety and Efficacy of Theranostic Agents in Solid Tumors With Active Brain Metastases (the THERANOVA Study; NMN-02).","THERANOVA","Inclusion Criteria\n\nTo be eligible to participate in this trial, an individual must meet ALL the following criteria:\n\n1. Patient, or legal representative (if applicable), must be capable to understand the purpose of the study and have signed written Informed Consent Form (ICF) prior to beginning specific protocol procedures.\n2. Male or female patients ≥ 18 years of age at the time of signing ICF.\n3. Radiologically documented locally advanced unresectable or metastatic breast cancer (BC).\n4. Histologically confirmed HER2-positive (HER2\\[+\\]) breast cancer based on local testing on the most recent analyzed biopsy according to the most recent American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guidelines.\n5. Untreated newly diagnosed or progressing brain metastasis (BM) after prior local therapy. Any number of brain lesions is acceptable as long as all the eligibility criteria are fulfilled.\n6. Measurable disease according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria, with at least one measurable brain lesion of ≥ 10 mm on T1-weighted, gadolinium-enhanced magnetic resonance imaging (MRI).\n7. Patients may or may not have type I leptomeningeal disease (LMD) per European Association of Neuro-Oncology (EANO)- European Society for Molecular Oncology (ESMO) criteria.\n8. Stable or decreasing corticosteroid dose, or no use of corticoids, for at least 7 days prior to enrollment.\n9. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2.\n10. Minimum life expectancy of ≥ 6 weeks at screening.\n11. Resolution of all acute toxic effects of prior anticancer therapy to grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v.5.0).\n\n    Note: except for alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion.\n12. Patient has adequate bone marrow, liver, and renal function within 7 days before first Study treatment dose:\n\n    I. Hematological (without platelet, red blood cell transfusion\u002Fplasma transfusion within 1 week prior to screening assessment, and\u002For granulocyte colony-stimulating factor support): White blood cell (WBC) count \\> 3.0 x 109\u002FL, absolute neutrophil count (ANC) ≥ 1.5 x 109\u002FL, platelet count ≥ 100.0 x109\u002FL, and hemoglobin ≥ 9.0 g\u002FdL (≥ 5.6 mmol\u002FL).\n\n    II. Hepatic: Serum albumin ≥ 2.5 g\u002FdL; total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 3 in patients with liver metastases or know history of Gilbert's disease); alkaline phosphatase (ALP) ≤ 2.5 times ULN (≤ 5 in patients with liver metastases); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 times ULN (≤ 5 in patients with liver metastases); international normalized ratio (INR) \\\u003C 1.5.\n\n    III. Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL\u002Fmin\u002F1.73 m2 based on Cockcroft-Gault glomerular filtration rate estimation for patients with creatinine levels above institutional normal.\n13. Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 14 days before Study treatment initiation. In addition, they must agree to use one highly effective method of birth control for the full duration of study participation.\n14. Male participants who are sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception for the full duration of study participation.\n15. Patients must be accessible for treatment and follow-up.\n\nExclusion Criteria\n\nAn individual who meets ANY of the following criteria will be excluded from participation in this trial:\n\n1. Participation in another clinical trial, interventional or observational, until the Study's safety visit (participation in retrospective studies or data analysis is allowed).\n2. Treatment with approved or investigational cancer therapy within 14 days prior to initiation of study drug.\n3. Known history of invasive malignancy and other than the malignancy of interest within 5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.\n4. Known allergy or hypersensitivity reaction to any investigational medicinal products (diagnostic radioligand) or their incorporated substances.\n5. Major surgical procedure or significant traumatic injury within 14 days before the first dose of study treatment or anticipation of need for major surgery within the course of the study treatment.\n6. Pregnant or breastfeeding females or patients not willing to apply highly effective contraception as defined in the protocol.\n7. Receipt of live or attenuated vaccine within 30 days prior to the first dose of study treatment.\n8. Has active or uncontrolled infection with hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients 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. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.\n9. Has known human immunodeficiency virus (HIV) infection that is not well controlled.\n10. Other active uncontrolled infection at the time of enrollment.\n11. Is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.\n12. A history of uncontrolled seizures, central nervous system (CNS) disorders, or serious and\u002For unstable pre-existing psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs or interfering with trial participant safety.\n13. Known substance abuse or any other concurrent severe and\u002For uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation.\n14. Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study.\n15. Inability or unwillingness to comply with the requirements of the protocol in the opinion of the investigator.",{"count":320,"type":21},10,[24],"This trial will evaluate treatment for patients with solid tumors with active brain metastases. Patients will be treated with a theranostic or diagnostic agent. Theranostic agents are targeted radioactive drugs used to identify (diagnose) and to deliver therapy. The main purpose of the study is to analyze the efficacy (to find out how effective a treatment is) of each of the theranostic agents in patients who have solid tumors with active brain metastases. In the diagnostic phase, the main objective is to determine the proportion of patients showing target expression in the brain lesion after a single dose of diagnostic agent. In the therapeutic phase, the theranostic agent's efficacy will be determined by assessing the response rate in the brain, defined as intracranial response rate at 24 weeks.",[324,325],"Solid Tumors","HER2-positive Breast Cancer",[317,327,328,329,330,331],"Platform trial","Active Brain Metastases","Theranostic Agents","Radioligand therapy","Radioligand imaging","2025-11-13",{"date":334,"type":34},"2025-11-14",{"date":336,"type":21},"2026-04-30",{"date":338,"type":21},"2028-12-31",{"name":40,"class":41},""]