[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"her2-positive-metastatic-breast-cancer\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:her2-positive-metastatic-breast-cancer":26},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,11,0,[8,41,92,121,142,166,196,219,292,319,341],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":14,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":29,"lastUpdatePostDateStruct":30,"startDateStruct":33,"completionDateStruct":35,"leadSponsor":37,"locationsCount":40},"100561853","phase-2-her2-molecular-imaging-with-89zr-trastuzumab-petct-as-a-predictive-biomarker-for-antibody-drug-conjugate-sequencing-in-patients-with-advanced-her2-positive-breast-cancer-100561853",false,"NCT06595563","HER2 Molecular Imaging With 89Zr-trastuzumab PET\u002FCT as a Predictive Biomarker for Antibody-drug Conjugate Sequencing in Patients With Advanced HER2-positive Breast Cancer","ZEPHIR-02","Inclusion Criteria:\n\n* ECOG performance status ≤ 1\n* Must have histologically or cytologically confirmed progressive advanced\u002Fmetastatic HER2-positive breast carcinoma as per the updated American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) guidelines according to local testing. HER2 status may be determined in the primary breast cancer tumour or, when not available, in a metastatic lesion.\n* Multifocal unilateral or bilateral breast adenocarcinoma tumours are allowed if all tested HER2-positive, according to local testing\n* Prior treatment with taxane, trastuzumab and pertuzumab (early or advanced setting) and T-DXd (metastatic setting). In order to be eligible, patients subjects must have received T-DXd as the last systemic metastatic treatment line before inclusion, and presented disease progression on this drug.\n\nPrior therapy with tucatinib, trastuzumab, and capecitabine, in advanced setting, is permissible, provided that T-DXd serves as the last systemic metastatic treatment line before inclusion, and patient subject presented disease progression on this drug.\n\n* Life expectancy ≥ 6 months.\n* At screening FDG-PET at least two \"target\" lesions are required to fulfil the following criteria: (1) anatomically transaxial diameter ≥ 1.5 cm and (2) metabolically assessable with a maximum standard uptake value corrected for lean body mass (SUVmax) ≥ 1.5 x SUVmean + 2 standard deviations (SD) of the liver measured in a 3-cm-diameter spherical volume of interest (VOI) in normal liver parenchyma.\n\nIn case of suspected liver metastasis, a lesion should have a SUVmax ≥ 2 x SUVmean + 3 SD of the blood pool measured in a 1 cm-diameter VOI within descending thoracic aorta. Lesions pre-treated with irradiation are not eligible for consideration as \"target\" lesions.\n\n* Adequate Bone Marrow Function including:\n\n  * Absolute Neutrophil Count (ANC) ≥1000\u002FμL or ≥1x109\u002FL.\n  * Platelets ≥100,000\u002FμL or ≥ 100 x 109\u002FL.\n  * Haemoglobin ≥ 9 g\u002FdL.\n* Adequate Renal Function including serum creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated creatinine clearance ≥ 60 ml\u002Fmin as calculated using the method standard for the institution.\n* Adequate Liver Function, including all the following parameters:\n\n  * Total serum bilirubin ≤ 1.5 x ULN unless the patient subject has documented Gilbert syndrome.\n  * Aspartate and Alanine Aminotransferase (AST and ALT) ≤ 2.5x ULN.\n* Current left ventricular ejection fraction (LVEF) ≥ 50% on echocardiography or multiple-gated acquisition scanning and no history of a LVEF \\\u003C 40% or symptomatic heart failure or a recent myocardial infarction.\n* Willingness to provide tumour tissue (mandatory biopsy) and blood samples (mandatory) for translational research activities.\n* Willingness to comply with the protocol for the duration of the study including treatment and scheduled visits and examinations.\n* Signed Informed Consent form (ICF) obtained prior to any study related procedure.\n\nInclusion criterion applicable to FRANCE only:\n\n* Affiliated to the French Social Security System\n\nExclusion Criteria:\n\n* Prior exposure to T-DM1 for the treatment of metastatic BC. For subjects exposed to T-DM1 for the treatment of early BC, subjects must not have relapsed while on or within 12 months of finishing treatment with T-DM1.\n* Brain metastasis as sole metastasis and\u002For symptomatic or requiring therapy to control symptoms.\n* History of interstitial lung disease \u002F pneumonitis (grade 3 or 4) during the prior treatment with T-DXd.\n* Cardiopulmonary dysfunction as defined by any of the following:\n\n  * Significant symptoms (Grade ≥ 2) relating to LV dysfunction, cardiac arrhythmia, or cardiac ischemia while or since receiving preoperative therapy.\n  * Uncontrolled hypertension (systolic blood pressure \\> 180 mmHg and\u002For diastolic blood pressure \\> 100 mmHg)\n  * Inadequately controlled angina, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease\n  * Screening LVEF \\\u003C 50% by either ECHO or MUGA\n  * History of NCI CTCAE (Version 4.0) Grade ≥ 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria Class ≥ II\n  * History of a decrease in LVEF to \\\u003C 40% or symptomatic CHF with prior trastuzumab treatment (e.g., during preoperative therapy)\n  * Myocardial infarction within 12 months prior to randomization\n  * Requirement for continuous oxygen therapy\n* Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to trastuzumab or excipients.\n* Contra-indication for treatment with T-DM1.\n* The number of subjects included in this trial, considered as \"rapid progressors\" (Rapid progressors defined as progressive disease within the first 6 months of T-DXd therapy) will be capped at 10% at enrolment (no more than 7 subjects out the 78 subjects planned to be recruited). After the first 7 \"rapid progressors\" included, progression within the first 6 months of T-DXd therapy will be considered as an exclusion criterion.\n* Any known liver disease, including known carriers of hepatitis B virus, hepatitis C, autoimmune hepatic disorders and sclerosing cholangitis.\n* Concurrent, serious, uncontrolled infections or known infection with HIV. Prior history of other invasive cancer in the past 5 years except basal or squamous cell carcinoma of skin that has been definitively treated.\n* Pregnant and\u002For lactating women, or intending to become pregnant during the study. Serum pregnancy test (for subjects of childbearing potential) positive within 15 days prior to enrolment.\n* Women of childbearing potential refusing to use one highly effective method of contraception from ICF signature, during the course of the study and at least 7 months after the last administration of T-DM1.\n* Men with childbearing potential partner refusing to use condom during the course of this study and for at least 7 months after the last administration of T-DM1.\n* Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.\n\nExclusion criterion applicable to FRANCE only:\n\n* Vulnerable persons according to the article L.1121-6 of the Public Health Code, adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the Public Health Code.","ALL","18 Years",{"count":19,"type":20},87,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","ZEPHIR-02 is a multicentre, open-label phase II study that will enroll subjects with HER2-positive advanced\u002Fmetastatic breast cancer (mBC) who have experienced disease progression under trastuzumab deruxtecan (T-DXd) in the metastatic setting.\n\nAll subjects will undergo baseline biopsy, blood collection, FDG-PET\u002FCT and 89Zr-trastuzumab PET\u002FCT (HER2-PET\u002FCT) and will be classified as HER2-PET\u002FCT positive or negative, as previously described in the ZEPHIR trial. Focusing on a central visual \"patient-based\" classification that captures the entire disease burden, a side-by-side display will be used, comparing baseline FDG-PET\u002FCT (which identifies all FDG-positive metastases regardless of their HER2-imaging status) and HER2-PET\u002FCT. Subjects will be categorized into two HER2-PET\u002FCT patterns (positive vs. negative) based on proportion of FDG-avid tumor load with significant 89Zr-trastuzumab uptake.\n\nSubjects classified as \"positive\" will receive T-DM1 as monotherapy, IV 3.6mg\u002Fkg every 3 weeks (21 days +- 3 days) until disease progression, unacceptable toxicity or request of the subject to withdraw from the study. FDG-PET\u002FCT will be performed before cycle 2 of T-DM1 will serve as a research tool to correlate metabolic changes with clinical outcomes. Other FDG-PET\u002FCT will be performed before cycle 4 of T-DM1 for assessment of response. Subjects who demonstrate a partial or complete response (responders) will continue treatment with T-DM1. Subjects who exhibit stable disease or disease progression (non-responders) will discontinue study treatment and enter the survival follow-up period. For responders, subsequent metabolic evaluations will be performed every 3 months, with FDG-PET\u002FCT. Treatment response will be assessed according to metabolic response. For these subjects, mandatory blood samples will be obtained at all metabolic reassessments. Subjects with HER2-PET\u002FCT classified as \"negative\" will receive treatment of physician's choice (TPC) as per the best local clinical practice and be out of the study.\n\nAll enrolled subjects will undergo a mandatory biopsy during the pre-treatment period.\n\nThe study also includes mandatory translational procedures (i.e. collection of tumour biopsy during pre-treatment period and blood samples at pre-specified time points) for exploratory molecular analyses.",[26,27],"HER2-positive Metastatic Breast Cancer","HER2-positive Advanced Breast Cancer","RECRUITING","2026-07-01",{"date":31,"type":32},"2026-07-02","ACTUAL",{"date":34,"type":20},"2026-06-30",{"date":36,"type":20},"2029-09",{"name":38,"class":39},"Jules Bordet Institute","OTHER",8,{"id":42,"slug":43,"hasResults":11,"nctId":44,"briefTitle":45,"officialTitle":46,"acronym":4,"eligibilityCriteria":47,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":48,"targetDuration":4,"studyType":21,"phases":50,"briefSummary":52,"conditions":53,"keywords":63,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":81,"lastUpdatePostDateStruct":82,"startDateStruct":84,"completionDateStruct":86,"leadSponsor":88,"locationsCount":91},"100564176","phase-1-open-label-study-of-bbo-10203-in-subjects-with-advanced-solid-tumors-100564176","NCT06625775","Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors","A Phase 1a\u002F1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-10203 in Subjects With Advanced Solid Tumors (The BREAKER-101 Study)","Inclusion Criteria:\n\n* Locally advanced and unresectable or metastatic HER2-positive advanced breast cancer (aBC), HR-positive\u002FHER2-negative advanced breast cancer, KRAS mutant advanced colorectal cancer (aCRC), or KRAS mutant advanced non-small cell lung cancer (aNSCLC)\n* Measurable disease by RECIST v1.1 (except for HR-positive HER2-negative aBC where evaluable bone-only disease is permitted)\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1\n* Adequate LVEF assessed by ECHO or MUGA (BBO-10203 + Trastuzumab cohorts only)\n* Stable brain metastases\n* Patients with HER2-positive aBC: Must have had at least 2 prior lines of anti-HER2-directed therapy. Only 1 prior line is acceptable where there is no other regionally available standard of care (SoC)\n* Monotherapy Cohort patients with HR-positive, HER2-negative aBC, KRAS mutant aCRC or aNSCLC: Must have progression on, or disease recurrence after at least one line of SOC treatment or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from SoC therapy\n* BBO-10203 + Fulvestrant combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, must have been treated with a CDK4\u002F6i\n* BBO-10203 + Fulvestrant + ribociclib combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, no prior systemic therapy in the aBC setting permitted\n* BBO-10203 + FOLFOX + Bevacizumab combination cohort patients with KRAS mutant aCRC: One prior line of irinotecan-containing therapy for locally advanced or metastatic CRC is allowed but not required\n\nExclusion Criteria:\n\n* Patients with KRAS mutant aCRC who have KRAS G12R mutation, BRAFV600E mutation, HER2amp, or dMMR\u002FMSI-H tumors\n* Patients with KRAS mutant aNSCLC who have KRAS G12R mutation, or tumors with other targetable driver mutations (eg, EGFR, anaplastic lymphoma kinase, ROS1\u002FBRAF\u002FRET\u002FMET\u002FEGFR exon20 insertion\u002FNTRK\u002FHER2)\n* Patients with untreated and\u002For non-stable brain metastases\n\nOther inclusion\u002Fexclusion criteria are specified in the protocol",{"count":49,"type":20},392,[51],"PHASE1","First in human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of BBO-10203, a PI3Kα:RAS breaker, alone and in combination with other anti-cancer agents in patients with advanced solid tumors.",[54,55,56,57,26,58,59,60,61,62,27],"Solid Tumor, Adult","Metastatic Breast Cancer","Advanced Breast Cancer","HER2 Mutation-Related Tumors","KRAS Mutant Metastatic Colorectal Cancer","Metastatic Lung Cancer","Metastatic Colorectal Cancer","Advanced Lung Cancer","HR-positive, HER2-negative Advanced Breast Cancer",[64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80],"BREAKER-101","BridgeBio Oncology Therapeutics","BBOT","Phase1","Phase 1a\u002F1b","Trastuzumab","Breast","Colorectal","Non-Small Cell Lung Cancer","CRC","NSCLC","Metastatic Cancer","Advanced Cancer","HER2-positive","HR-positive","HR-positive, HER2-negative","HER2-negative","2026-06-18",{"date":83,"type":32},"2026-06-23",{"date":85,"type":32},"2024-10-29",{"date":87,"type":20},"2028-11",{"name":89,"class":90},"TheRas, Inc., d\u002Fb\u002Fa BBOT (BridgeBio Oncology Therapeutics)","INDUSTRY",40,{"id":93,"slug":94,"hasResults":11,"nctId":95,"briefTitle":96,"officialTitle":97,"acronym":4,"eligibilityCriteria":98,"healthyVolunteers":11,"sex":99,"minAge":17,"maxAge":100,"enrollmentInfo":101,"targetDuration":4,"studyType":21,"phases":103,"briefSummary":104,"conditions":105,"keywords":108,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":111,"lastUpdatePostDateStruct":112,"startDateStruct":114,"completionDateStruct":116,"leadSponsor":118,"locationsCount":120},"100637795","phase-2-dalpiciclib-anti-her2-therapy-and-endocrine-therapy-for-hormone-receptor-positive-her2-positive-metastatic-breast-cancer-100637795","NCT07610720","Dalpiciclib, Anti-HER2 Therapy, and Endocrine Therapy for Hormone-Receptor-Positive, HER2-Positive Metastatic Breast Cancer","Evaluating the Efficacy and Safety of Dalpiciclib Plus Anti-HER2 Therapy and Endocrine Therapy in Patients With Induction-Treated Hormone-Receptor-Positive, HER2-Positive Metastatic Breast Cancer","Inclusion Criteria:\n\n1. Females aged 18 to 75 years with pathologically confirmed metastatic or locally advanced unresectable breast cancer.\n2. Hormone receptor (HR)-positive and HER2-positive.\n3. Patients with no evidence of disease progression (including CR, PR, or SD)after 4-8 cycles of first-line systemic anti-tumor therapy.\n4. ECOG Performance Status: 0-1.\n\nExclusion Criteria:\n\n1. Symptomatic active brain metastases or extensive leptomeningeal metastases.\n2. History of Grade 3 or 4 allergic reaction related to the study drugs.\n3. Currently receiving other anti-tumor therapies.","FEMALE","75 Years",{"count":102,"type":20},57,[23],"Efficacy and Safety of Dalpiciclib Combined with Anti-HER2 Targeted Therapy and Endocrine Therapy as First-line Maintenance Treatment for Patients with Recurrent or Metastatic Hormone-Receptor-Positive, HER2-positive Breast Cancer.",[106,107],"Advanced\u002FMetastatic Breast Cancer","HER2-Positive Metastatic Breast Cancer",[109,110],"Dalpiciclib","Dalpiciclib Plus Anti-HER2 Therapy and Endocrine Therapy","2026-05-20",{"date":113,"type":32},"2026-05-28",{"date":115,"type":20},"2026-06-01",{"date":117,"type":20},"2029-11-01",{"name":119,"class":39},"Sun Yat-sen University",1,{"id":122,"slug":123,"hasResults":11,"nctId":124,"briefTitle":125,"officialTitle":125,"acronym":4,"eligibilityCriteria":126,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":127,"targetDuration":4,"studyType":129,"phases":4,"briefSummary":130,"conditions":131,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":132,"lastUpdatePostDateStruct":133,"startDateStruct":135,"completionDateStruct":137,"leadSponsor":139,"locationsCount":141},"100558438","quantifyher-quantitative-immunofluorescence-andor-rt-qpcr-for-measuring-her2-in-her2-low-metastatic-breast-cancer-100558438","NCT06551116","QuantifyHER: Quantitative Immunofluorescence and\u002For RT-qPCR for Measuring HER2 in HER2-low Metastatic Breast Cancer","Inclusion Criteria:\n\n* Women and men age \\> 18 years\n* Metastatic breast cancer, histologically- confirmed. Any estrogen receptor (ER) status is allowed. ER status will be determined by local laboratory assessment utilizing ASCO\u002FCAP guidelines.\n* Primary and\u002For metastatic tumor with 1+ level of expression of HER2 by immunohistochemistry as determined by local laboratory assessment utilizing ASCO\u002FCAP guidelines.\n* Measurable disease by cross-sectional imaging at the start of treatment. Patients with measurable bone-only disease or active brain metastases are eligible.\n* Archival tissue available for biomarker assessment. One specimen should be the most recent metastatic biopsy. If HER2 1+ status was determined on a different specimen (either primary or metastatic tissue), that specimen is also required. Samples obtained from bone metastases that were processed via decalcification methods are not eligible.\n* Intention to initiate therapy with T-DXd (Enhertu) at FDA-approved dose and schedule as next line of therapy. If T-DXd was already initiated, patients must be registered within 30 days of initiation.\n* Ability to provide informed consent\n\nExclusion Criteria:\n\n* Concurrent Her2-overexpressing metastatic breast cancer (as confirmed by a metastatic biopsy with IHC 3+ or IHC 2+ with FISH amplified as per standard ASCO\u002FCAP guidelines)",{"count":128,"type":20},200,"OBSERVATIONAL","This study will assess whether a quantitative, HER2 assay can accurately and reliably discriminate between responders and non-responders among patients with HER2 IHCI+ metastatic breast cancer who are receiving T-Dxd.",[26],"2026-04-02",{"date":134,"type":32},"2026-04-07",{"date":136,"type":32},"2024-10-10",{"date":138,"type":20},"2029-09-01",{"name":140,"class":39},"Abramson Cancer Center at Penn Medicine",37,{"id":143,"slug":144,"hasResults":11,"nctId":145,"briefTitle":146,"officialTitle":147,"acronym":148,"eligibilityCriteria":149,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":150,"targetDuration":4,"studyType":21,"phases":152,"briefSummary":154,"conditions":155,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":157,"lastUpdatePostDateStruct":158,"startDateStruct":160,"completionDateStruct":162,"leadSponsor":164,"locationsCount":120},"100631671","survey-cns-a-feasibility-study-of-randomising-women-and-men-with-her2-positive-metastatic-breast-cancer-to-central-nervous-system-surveillance-versus-no-surveillance-100631671","NCT07503717","SURVEY-CNS: A Feasibility Study of Randomising Women and Men With HER2-Positive Metastatic Breast Cancer to Central Nervous System Surveillance Versus No Surveillance","SURVEY-CNS: A Feasibility Study of Randomising Women and Men With HER2-Positive Metastatic Breast Cancer to Central Nervous System Surveillance Versus No Surveilla","SURVEY-CNS","Inclusion Criteria:\n\n* Age ≥18 years\n* Male or female\n* Histologically or cytologically confirmed HER2-positive breast cancer\n* Evidence of metastatic breast cancer\n* Estrogen receptor (ER) positive or negative disease permitted\n* Presence of visceral metastatic disease\n* Receiving active HER2-directed systemic therapy\n* Eastern Cooperative Oncology Group (ECOG) performance status 0-2\n* Estimated life expectancy greater than 6 months\n* Ability to provide written informed consent\n* Willing and able to comply with study procedures and follow-up\n\nExclusion Criteria:\n\n* Prior history of brain metastases\n* History or evidence of leptomeningeal carcinomatosis\n* Symptoms suggestive of brain metastases at screening\n* Bone-only metastatic disease\n* Inability to undergo MRI scanning\n* Known hypersensitivity or contraindication to MRI contrast agents that cannot - be managed per local standard of care\n* Significant medical condition or laboratory abnormality that, in the opinion of - the investigator, makes participation inappropriate Inability to provide informed consent\n* Deemed unsuitable for participation by the principal investigator due to clinical, mobility, or social circumstances",{"count":151,"type":20},69,[153],"NA","SURVEY-CNS is a feasibility study evaluating whether women and men with HER2-positive metastatic breast cancer can be successfully recruited and randomised to a strategy of central nervous system (CNS) magnetic resonance imaging (MRI) surveillance versus standard of care (no routine CNS surveillance).\n\nPatients with HER2-positive metastatic breast cancer have a high risk of developing brain metastases. Brain metastases can cause significant symptoms, including headache, nausea, seizures, visual disturbance, motor dysfunction, and cognitive or psychological changes. Although new HER2-directed therapies have improved systemic disease control, CNS progression remains common and is associated with reduced quality of life and survival.\n\nCurrently, routine brain imaging is not recommended in asymptomatic patients. Brain imaging is typically performed only when neurological symptoms develop. Observational data suggest that patients diagnosed with asymptomatic brain metastases may have better outcomes than those diagnosed after symptoms occur. However, it is not known whether a surveillance strategy is feasible or acceptable to patients.\n\nAll participants in this study will undergo a baseline contrast-enhanced brain MRI. Patients without evidence of CNS metastases on the baseline scan will be randomised (1:1) to either:\n\nCNS surveillance with repeat brain MRI at 6 and 12 months, or No routine surveillance imaging (standard of care), with imaging only if clinically indicated.\n\nThe primary objective is to determine whether more than 30% of eligible patients approached agree to undergo screening and randomisation. The study will approach up to 193 patients and will be considered feasible if 69 patients consent to screening with intent to randomise.\n\nSecondary objectives include:\n\nDetermining the proportion of patients with previously undetected (occult) CNS metastases at baseline; Determining the incidence of occult CNS metastases during surveillance; Recording symptomatic CNS presentations; Describing management of CNS metastases, including surgery or radiotherapy. Participants will be followed for 14 months from baseline.",[156,107],"Breast Cancer","2026-03-26",{"date":159,"type":32},"2026-03-31",{"date":161,"type":32},"2025-06-01",{"date":163,"type":20},"2028-06-01",{"name":165,"class":39},"Royal College of Surgeons, Ireland",{"id":167,"slug":168,"hasResults":11,"nctId":169,"briefTitle":170,"officialTitle":171,"acronym":172,"eligibilityCriteria":173,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":174,"targetDuration":4,"studyType":21,"phases":176,"briefSummary":177,"conditions":178,"keywords":181,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":187,"lastUpdatePostDateStruct":188,"startDateStruct":190,"completionDateStruct":192,"leadSponsor":194,"locationsCount":5},"100500747","phase-2-capecitabine-tucatinib-and-intrathecal-trastuzumab-for-breast-cancer-patients-with-leptomeningeal-disease-100500747","NCT05800275","Capecitabine, Tucatinib, and Intrathecal Trastuzumab for Breast Cancer Patients With Leptomeningeal Disease","Multicentric Single Arm Phase II Study Evaluating the Efficacy of Association of Tucatinib, Capecitabine and Intra-CSF Trastuzumab in HER2 Amplified Breast Cancer Patients With Leptomeningeal Metastases","ETIC-LM","Inclusion Criteria:\n\n1. Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent;\n2. Patients ≥18 years old;\n3. Histologically confirmed metastatic breast cancer;\n4. Histologically confirmed HER2 positive breast cancer, with HER2 positive defined by in situ hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ hybridization (FISH) methodology; Note: HER2 testing should be performed preferably metastatic site; any estrogen and progesterone (ER\u002FPR) status is allowed;\n5. Proven leptomeningeal progression defined by linear leptomeningeal metastases on magnetic resonance imaging (MRI) or the presence of breast cancer cells in CSF (obtained within 28 days before inclusion );\n6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2;\n7. Life expectancy ≥2 months;\n8. Stable dose of steroids for at least 5 days prior to registration;\n9. If symptomatic brain or leptomeningeal metastasis, local treatment (surgery, radiation therapy) is allowed until 2 weeks before inclusion but should have been completed no more than 8 weeks before inclusion and with no clinical indication for immediate re-treatment with local therapy in the opinion of the investigator;\n10. Adequate hematological function within 14 days before inclusion: Absolute neutrophil count (ANC) ≥1.5 x 10⁹\u002FL; platelets count ≥100 x 10⁹\u002FL; and hemoglobin ≥9.0 g\u002FdL;\n11. Adequate liver function within 14 days before inclusion: total bilirubin ≤1.5 ULN (unless documented Gilbert's syndrome); AST and ALT ≤2.5 ULN (≤5 ULN in the presence of liver metastases);\n12. Normal renal function within 14 days before inclusion: estimated creatinine clearance ≥60 mL\u002Fmin according to the Cockcroft-Gault formula;\n13. Adequate cardiac function:\n\n    * 12 Lead electrocardiograms (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention\n    * QT\u002FQTc interval ≤470 msec for woman and ≤450 msec for men (mean of replicate values, correction per institutional standard) on the ECG at the screening visit and a normal kaliemia\n    * Left ventricular ejection fraction (LVEF) ≥55%\n    * No history of Torsades de Pointes or other symptomatic QTc abnormality\n14. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to National cancer institute-Common terminology criteria for adverse events (NCI-CTCAE) version 5.0 grade 1 or 0 to baseline (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion);\n15. Women of childbearing potential must have a negative pregnancy test (blood or urine test) within 14 days prior to inclusion;\n16. Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of trial participation and up to 7 months after completing treatment\u002Ftherapy. Hormonal contraceptives such as birth control pills, patches, implants, or injections are not allowed in patients who are hormone receptor positive;\n17. Patients affiliated to the social security system (or equivalent);\n18. Patient must be willing and able to comply with the protocol for the duration of the trial including scheduled visits, treatment plan, laboratory tests, and examinations including follow-up.\n\nExclusion Criteria:\n\n1. Used of a strong cytochrome P450 (CYP)2C8 inhibitor within 5 half-lives of the inhibitor, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment. Use of sensitive CYP3A substrates should be avoided one week before enrollment and during study treatment;\n2. Previous treatment with Tucatinib or Capecitabine;\n3. Severe leukopenia, neutropenia, or thrombocytopena, severe hepatic impairment, severe renal impairment (creatinine clearance below 30mL\u002Fmin)\n4. Recent or concomitant treatment with brivudine ;\n5. Any antiplatelet or curative anticoagulant treatment for blood coagulation disorders;\n6. Severe pre-existing cerebrovascular dysfunction or pathology such as stroke and intra-cerebral hematoma or uncontrolled intracerebral hypertension induced by brain metastasis;\n7. Ventriculoperitoneal or atrial shunt, except if the valve is equipped with an on-off device and that the patient's condition allows for to remain in the off position for 6 hours after each injection of trastuzumab;\n8. Known history of testing positive for HIV or known acquired immunodeficiency syndrome;\n9. Carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease;\n10. Uncontrolled hypertension;\n11. Uncontrolled infection;\n12. Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy;\n13. Pregnant or breast-feeding women;\n14. Known prior severe hypersensitivity to tucatinib or compounds chemically or\u002Fand biologically similar or any component in its formulation;\n15. Hypersensitivity to trastuzumab, murine proteins, or to any of the excipients in its formulation;\n16. Known prior severe hypersensitivity to capecitabine or to any of the excipients or fluorouracil;\n17. Known complete dihydropyrimidine dehydrogenase (DPD) deficiency (if applicable);\n18. Inability to swallow tablets or significant gastrointestinal disease which would preclude the adequate oral absorption of medications;\n19. Prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease for at least 5 years;\n20. Person deprived of their liberty or under protective custody or guardianship;\n21. Participation in another therapeutic trial within the 30 days prior to treatment initiation;\n22. Patients with any other disease or illness, which requires hospitalization or is incompatible with the trial treatment, are not eligible. Patients unwilling or unable to comply with trial obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the trial.",{"count":175,"type":20},30,[23],"The goal of this clinical trial is to evaluate the efficacy of tucatinib and capecitabine in combination with intrathecal trastuzumab on overall survival rate at 12 months in HER2-positive metastatic breast cancer (MBC) patients with proven leptomeningeal evolution and requiring intrathecal therapy.",[179,180,26],"Leptomeningeal Metastasis","Leptomeningeal Disease",[182,180,183,179,184,185,186,26],"Intrathecal injection","Breast Cancer Metastatic","Intrathecal trastuzumab","Capecitabine","Tucatinib","2025-11-14",{"date":189,"type":32},"2025-11-18",{"date":191,"type":32},"2023-12-18",{"date":193,"type":20},"2027-06",{"name":195,"class":39},"UNICANCER",{"id":197,"slug":198,"hasResults":11,"nctId":199,"briefTitle":200,"officialTitle":201,"acronym":202,"eligibilityCriteria":203,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":204,"targetDuration":4,"studyType":21,"phases":206,"briefSummary":207,"conditions":208,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":210,"lastUpdatePostDateStruct":211,"startDateStruct":213,"completionDateStruct":215,"leadSponsor":217,"locationsCount":120},"100512964","discontinuation-of-maintenance-her-2-directed-therapy-in-long-term-survivors-of-metastatic-her-2-positive-breast-cancer-100512964","NCT05959291","Discontinuation of Maintenance HER-2 Directed Therapy in Long-Term Survivors of Metastatic HER-2 Positive Breast Cancer","Free-HER: Discontinuation of Maintenance HER-2 Directed Therapy in Long-Term Survivors of Metastatic HER-2 Positive Breast Cancer","Free-HER","Inclusion Criteria:\n\n1. Patients with a diagnosis of HER-2 positive metastatic (Stage IV) breast cancer.\n2. Patients in complete radiological remission (CRR), including a stable bone scan, as determined by computed tomography (CT), positron-emission tomography (PET), or PET-CT.\n\n   a. Patients with brain metastasis are allowed to participate as long as their disease has been treated and radiologically stable for at least 36 months.\n3. Patients must be on the same or current anti-HER-2 directed therapy for at least 36 months.\n4. Archived tumor biopsy available.\n5. Patients with no evidence of circulating tumor deoxyribonucleic acid (ctDNA) as determined by the Signatera assay.\n6. Patients willing to stop maintenance anti-HER-2 directed therapy with close monitoring.\n7. Patients with an Eastern Cooperative Oncology Group (ECOG) performance score from 0 to 2.\n8. Patients ≥ 18 years of age.\n9. Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n1. Patients with uncontrolled metastatic disease.\n2. Patients whose disease has been controlled for less than 36 months on the same or current anti-HER-2 therapy.\n3. Patients who are currently receiving or have received treatment for a secondary cancer other than resected non-melanoma skin cancer lesions or in situ cancer within the past 24 months.\n4. Patients positive for ctDNA (which occurs when a patient's blood sample contains ≥2 target markers) with the Signatera assay.\n5. Use of investigational drugs ≤ 28 days prior to study enrollment and during the study.\n6. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or that makes participation in the trial to be not in the best interest of the patient in the opinion of the Investigator.\n7. Patients with impaired decision-making capacity.\n\nPatients who are found to be ctDNA+ at study entry will be recorded as a screen failure (Section 5.4). Their Signatera testing results will be provided to their treating physician to aid in clinical decision-making for disease management and treatment.",{"count":205,"type":20},20,[153],"The purpose of this preliminary research study is to see if patients discontinuing maintenance Herceptin and\u002For other anti-HER-2 treatments with monitoring in addition to radiologic imaging and routine blood work will stay in complete radiological remission and to determine how long patients are able to stay in complete radiological remission without treatment.",[26,209],"Stage IV Breast Cancer","2025-08-11",{"date":212,"type":32},"2025-08-13",{"date":214,"type":32},"2023-07-17",{"date":216,"type":20},"2029-07-31",{"name":218,"class":39},"University of Miami",{"id":220,"slug":221,"hasResults":11,"nctId":222,"briefTitle":223,"officialTitle":224,"acronym":225,"eligibilityCriteria":226,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":227,"targetDuration":4,"studyType":21,"phases":229,"briefSummary":230,"conditions":231,"keywords":248,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":282,"lastUpdatePostDateStruct":283,"startDateStruct":285,"completionDateStruct":287,"leadSponsor":289,"locationsCount":291},"100505964","phase-1-pre-i-spy-phase-iib-oncology-platform-program-100505964","NCT05868226","PRE-I-SPY Phase I\u002FIb Oncology Platform Program","PRE-Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis: A Phase I\u002FIb Platform Trial","PRE-I-SPY-PI","General Inclusion Criteria (GIC):\n\n* GIC1: The participant must have ability to understand and willingness to provide signed written informed consent prior to any study related assessments and procedures and for collection of archival FFPE blocks (freshly cut 14 unstained tumor slides would be acceptable).\n* GIC2: Age ≥ 18 years at the time of signing the informed consent\n* GIC3: Gender: Male or female (premenopausal and postmenopausal)\n* GIC4: ECOG performance status Grade 0-2\n* GIC5: Estimated life expectancy \\> 12 weeks at the start of investigational medicinal product (IMP) treatment.\n* GIC6: Adequate organ function, evidenced by the following laboratory results within 30 days of the start of IMP:\n\n  * Absolute neutrophil count ≥ 1,500\u002Fmm3\n  * Platelet count ≥ 100,000\u002Fmm3\n  * Hemoglobin ≥ 9.0 g\u002FdL with no blood transfusion in the past 28 days\n  * Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)\n  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN\n  * Estimated Creatinine clearance (using Cockcroft-Gault formula) ≥ 60 mL\u002Fmin for small molecules and \\>30 mL\u002Fmin for monoclonal antibodies unless otherwise specified in the Arm Specific Eligibility.\n\nThese cut-off values may be modified with supporting data for specific drug regimens.\n\n* GIC7: Non-Pregnant: Serum or urine pregnancy test must be negative within 14 days of IMP treatment start in women of childbearing potential. Pregnancy testing does not need to be pursued in patients who are judged as postmenopausal before enrollment, or who have undergone bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation. If male, they must agree to refrain from donating sperm during treatment.\n* GIC8: Contraception: Women of childbearing potential and men must be willing to use adequate contraception for the duration of protocol treatment. Additional information regarding contraception for the specific treatment arm will be added to the drug arm description. Adequate contraception is defined as one highly effective form (i.e., abstinence, (fe)male sterilization) OR two effective forms (e.g., non-hormonal IUD and condom \u002F occlusive cap with spermicidal foam \u002F gel \u002F film \u002F cream \u002F suppository).\n* GIC9: Prior therapy effects: Resolution of all acute toxic effects of prior therapy, including radiotherapy, to grade ≤1 and neuropathy to grade ≤2 (except toxicities not considered a safety risk for the patient) and recovery from surgical procedures.\n* GIC10: Participant compliance: Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.\n* Additional arm specific inclusion criteria as needed by drug arm regimen\n\nGeneral Exclusion Criteria (GEC):\n\n* GEC1: Wash out periods: No other anticancer therapy within the following periods:\n\n  * chemotherapy or investigational agents, 3 weeks\n  * mitomycin C and nitrosoureas, 6 weeks\n  * radiotherapy, 3 weeks\n  * targeted therapy, 2 weeks\n  * MAbs, ADCs, and immunotherapy, 3 weeks\n  * endocrine therapy, no washout needed\n* GEC2: Concurrent therapy with other Investigational Products.\n* GEC3: Prior history of drug\u002Fregimen hypersensitivity: History of infusion-related reactions and\u002For hypersensitivity to IMP or excipients of the study drug\u002Fdrugs which led to permanent discontinuation of the treatment.\n* GEC4: Uncontrolled intercurrent illness including (active infection, diabetes, pulmonary embolism in the past 6 months, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements).\n* GEC5: Cardiovascular disease: History (within 6 months prior to start IMP) of clinically significant cardiovascular disease such as unstable angina, congestive heart failure (CHF), myocardial infarction, uncontrolled hypertension, cardiac arrhythmia requiring medication, or baseline corrected QT by Fridericia's formula (QTcF) length \\> 470 msec for men and women. The QTcF cut-off value may be modified with supporting data for specific drug regimens.\n* GEC6: CNS tumoral spread: Active uncontrolled\u002Fsymptomatic central nervous system cancer\u002Fspinal cord compression. Previously treated and clinically stable lesions, as per Investigator's judgment, are permitted. Newly discovered asymptomatic lesions that are not life threatening and do not require urgent local treatment to ensure patient safety, after consultation with study regimen chaperones, may be permitted.\n* GEC7: Liver disease: Patients with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis.\n* GEC8: Recent major surgery within 4 weeks prior to start IMP treatment\n* GEC9: Pregnancy or breastfeeding\n* GEC10: Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.\n* GEC11: Other conditions, which in the opinion of the investigator, would compromise the safety of the patient or the patient's ability to complete the study.\n* GEC12: Concomitant malignancies: A diagnosis of a malignancy in the 2 years prior to starting study treatment other than the disease under study. Exceptions include indolent or definitively treated malignancy not expected to require treatment during the study, affect the safety of subjects, or affect the endpoints of the trial.\n* Additional arm specific exclusion criteria as needed by drug arm regimen",{"count":228,"type":20},124,[51],"I-SPY Phase I\u002FIb (I-SPY-P1) is an open-label, multisite platform study designed to evaluate single agents or combinations in a metastatic treatment setting that may be relevant for breast cancer patients with the overall goal of moving promising drug regimens into the I-SPY 2 SMART Design Trial (NCT01042379) and\u002For other oncology-based trials in a timely manner.",[232,75,55,233,26,57,234,235,236,237,238,239,240,241,242,54,243,244,245,246,247],"HER2-positive Breast Cancer","Metastatic","HER-2 Protein Overexpression","HER2-negative Breast Cancer","Triple Negative Breast Cancer","HR Positive","Hormone Receptor-positive Breast Cancer","Estrogen Receptor Positive Tumor","Progesterone Receptor-positive Breast Cancer","Hormone Receptor Negative Breast Carcinoma","Solid Tumor","Solid Carcinoma","HER2 Low Breast Cancer","HER2 Low Breast Carcinoma","ER Positive Breast Cancer","PR-positive Breast Cancer",[249,250,251,252,253,254,255,256,257,258,259,260,261,262,263,264,265,266,267,268,269,270,271,272,273,274,275,276,277,186,278,279,280,281],"I-SPY Trials","Quantum Leap Healthcare Collaborative","QLHC","I-SPY","I-SPY2","I-SPY1","PRE-ISPY","PRE-I-SPY","I-SPY Phase 1","I-SPY Phase 1b","I-SPY-P1","ISPY","ISPYP1","I-SPY Phase 1 Platform","ISPY2","ISPY1","Phase 1 Platform","Phase 1 Oncology Platform","T-DXd naive","PRE1","PRE2","PRE3","PRE","PRE-I-SPY Phase 1","PRE-I-SPY Phase 1b","ALX148","T-DXd","Enhertu","Zanidatamab","Ziihera","Tukysa","Evorpacept","QL","2025-04-01",{"date":284,"type":32},"2025-04-04",{"date":286,"type":32},"2023-02-15",{"date":288,"type":20},"2029-12-30",{"name":290,"class":39},"QuantumLeap Healthcare Collaborative",7,{"id":293,"slug":294,"hasResults":11,"nctId":295,"briefTitle":296,"officialTitle":297,"acronym":4,"eligibilityCriteria":298,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":100,"enrollmentInfo":299,"targetDuration":4,"studyType":21,"phases":301,"briefSummary":302,"conditions":303,"keywords":305,"overallStatus":309,"whyStopped":4,"lastUpdateSubmitDate":310,"lastUpdatePostDateStruct":311,"startDateStruct":312,"completionDateStruct":314,"leadSponsor":316,"locationsCount":4},"100567097","phase-2-arx788-in-her2-positive-metastatic-breast-cancer-patients-100567097","NCT06663748","ARX788 in HER2-positive Metastatic Breast Cancer Patients","Evaluate the Efficacy and Safety of ARX788 Given Every 6 Weeks in Patients with HER2-positive Advanced Breast Cancer","Inclusion Criteria:\n\n* 18 to 75 years old (including upper and lower limits), male or female;\n* Unresectable locally advanced, recurrent or metastatic BC;\n* Has previously received ≤ two lines of chemotherapy (excluding hormone therapy) for recurrent or metastatic BC;\n* Tissue samples determined to be HER2 positive (defined as IHC3+ or FISH+);\n* Has at least one measurable target lesion as per RECIST1.1 criteria;\n* Has recovered from any AE (≤ Grade 1) related to prior surgery and prior cancer treatment;\n* Adequate bone marrow, liver, kidney and coagulation function;\n* ECOG Performance Status Score of 0-1;\n* Voluntarily sign the informed consent, have good compliance and are willing to comply with the follow-up visit.\n\nExclusion Criteria:\n\n* Has known history to be allergic to any active ingredient or excipient of ARX788;\n* With meningeal metastases or disseminated brain metastases or active brain metastases, who need radiation, surgery or drug therapy;\n* Has pericardial effusion, pleural effusion or ascites effusion with clinical symptoms, signs or require symptomatic treatment;\n* Has interstitial lung disease requiring steroid therapy, a history of drug-induced interstitial lung disease, a history of radiation pneumonitis, or any evidence indicating clinically active interstitial lung disease;\n* Has any eye disease that require medical intervention such as keratitis, corneal diseases or active eye infection;\n* Has cardiac insufficiency;\n* Uncontrolled hypertension;\n* Has evidence of severe or uncontrollable systemic diseases;\n* Received live vaccines within 4 weeks before the first use of the investigational product or plans to receive live vaccines during the trial;\n* Breastfeeding female, or who has childbearing potential with a positive baseline pregnancy test or who is unwilling to use effective contraception during the trial;\n* Is unwilling or unable to stop wearing corneal contact lens during the trial;\n* Has received any systemic anti-tumor therapy (with the exception of endocrine therapy, with an interval of at least 7 days) within 28 days (or at least 5 half-lives) before the first use of the investigational product;\n* Has any mental or cognitive disorder that may restrict his\u002Fher understanding and execution of the informed consent form;\n* Other conditions that the Investigator considers inappropriate for participation in this trial, such as poor compliance.",{"count":300,"type":20},44,[23],"A phase 2 study of ARX788 given every 6 weeks in HER2-positive, metastatic breast cancer patients.",[304],"HER2-positive, Metastatic Breast Cancer",[306,307,308],"ARX788","HER2-positive breast cancer","Q6W","NOT_YET_RECRUITING","2024-10-27",{"date":85,"type":32},{"date":313,"type":20},"2024-11-20",{"date":315,"type":20},"2029-11-20",{"name":317,"class":318},"Henan Cancer Hospital","OTHER_GOV",{"id":320,"slug":321,"hasResults":11,"nctId":322,"briefTitle":323,"officialTitle":324,"acronym":325,"eligibilityCriteria":326,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":327,"targetDuration":4,"studyType":21,"phases":329,"briefSummary":330,"conditions":331,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":332,"lastUpdatePostDateStruct":333,"startDateStruct":335,"completionDateStruct":337,"leadSponsor":339,"locationsCount":120},"100538995","phase-1-dose-expansion-modular-study-to-explore-the-safety-tolerability-and-anti-tumor-activity-of-her3--dxd-monotherapy-and-combinations-in-patients-with-inoperable-advanced-breast-cancer-abc-after-progression-on-t-dxd-100538995","NCT06298084","Dose-Expansion Modular Study To Explore the Safety, Tolerability, and Anti-tumor Activity of HER3- DXd Monotherapy and Combinations in Patients With Inoperable Advanced Breast Cancer (ABC) After Progression on T-DXd","Phase 1b\u002F2, Multicenter, Open-label, Dose-Expansion Modular Study To Explore the Safety, Tolerability, and Anti-tumor Activity of HER3- DXd Monotherapy and Combinations in Patients With Inoperable Advanced Breast Cancer (ABC) After Progression on T-DXd","ICARUSBREAST02","Inclusion Criteria:\n\n1. Patients must have received prior treatment with T-DXd and presented disease progression while on T-DXd treatment or within 2 months from T-DXd interruption\u002Fdiscontinuation for any reason, without requiring to be the last line of treatment. Patients who have received other lines of treatment after T-DXd and before study entry is capped at 10 patients for each cohort.\n2. Patients with HER2-positive tumors must have received prior treatment with trastuzumab and taxanes. They may have received prior treatment with T-DM1 and pertuzumab.\n3. Patients with HER2-low tumors must have been treated with taxanes. Patients with HR-positive tumors must have received ET and CDK4\u002F6 inhibitors (patients may have received prior treatment with sacituzumab govitecan) If a patient has a tumor that was previously HER2-pos and became HER2-low, she\u002Fhe will be included in cohort 2 and meet the inclusion criteria for HER2-low tumors.\n\n   If a patient has a tumor that was previously HR-pos and became HR-neg, prior therapy with CDK4\u002F6 inhibitors is not mandatory.\n4. Patients with germline pathogenic BRCA1\u002F2 mutations and HER2-positive or HER2-low breast cancer are eligible to the study but must have received a prior treatment with PARP inhibitor (olaparib or talazoparib)\n5. Female or male patient aged ≥18 years on the day of the ICF signature\n6. Patient who has histologically confirmed diagnosis of breast cancer with unresectable loco regional or metastatic disease\n7. Patient must have an ECOG PS ≤1 at the time of screening\n8. Patients must have HER2-pos (IHC 3+ or IHC2+\u002FISH positive) or HER-2 low (IHC2+\u002FISH negative or IHC 1+) tumors with any HR status, any time before T-DXd exposure\n9. Patient must have at least one radiologically measurable lesion (different from the biopsy site) according to response evaluation criteria in solid tumors (RECIST) V1.1 criteria. At least one predominantly lytic or mixed lytic-blastic bone lesion with identifiable soft tissue component that can be evaluated by Computerized Tomography (CT)\u002FMagnetic Resonance Imaging (MRI) must be present in patients with only bone metastasis\n10. Patient must have a tumor site easily accessible to biopsy, avoiding bone biopsy when possible. Patients must have accepted to perform pre-treatment, on-treatment, and end-of-treatment biopsies\n11. Patient must have adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to Cycle 1, Day 1, defined per the protocol\n12. Female patients of reproductive\u002Fchildbearing potential must have a negative pregnancy test at screening (serum test within 24 hours before C1D1 or urine test within 72 hours of C1D1) and must and must agree to use a highly effective form of contraception or avoid intercourse during and till the end of treatment and for at least 8 months after the last dose of study drug. The following contraception methods are considered highly effective:\n\n    1. Intrauterine device (IUD)\n    2. Bilateral tubal occlusion\n    3. Vasectomized partner\n    4. Complete sexual abstinence defined as refraining from heterosexual intercourse during and till the end of treatment and for at least 8 months for females after the last dose of study drug. Periodic abstinence not an acceptable method of contraception\n13. Female patients must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 8 months after the final study drug administration\n14. Male patients must be surgically sterile or must withhold heterosexual intercourse, or must be willing to use a highly effective birth control upon enrollment, during the treatment period, and for at least 5 months following the last dose of study drug\n15. Male patients must not freeze or donate sperm starting at screening and throughout the study period, and for at least 5 months after the final study drug administration.\n16. Patient must understand, sign and date the written informed consent form (ICF) prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedure as per protocol\n17. Patient must be affiliated to a social security system or beneficiary of the same\n\nExclusion Criteria:\n\nThe following exclusion criteria are applicable for all modules. Patients will be excluded if they present one of them:\n\n1. Patient with a breast cancer amenable for resection or radiation therapy with curative intent\n2. Patient with any history of ILD (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have ILD as assessed by imaging during screening\n3. Patient with clinically severe pulmonary compromise (based on investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:\n\n   1. Any underlying pulmonary disorder (eg, pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion) OR\n   2. Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis) OR\n   3. Prior pneumonectomy\n4. Patient receiving chronic systemic corticosteroids dosed at \\>10 mg\u002Fday prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Patients who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study\n5. Patient with evidence of any leptomeningeal disease\n6. Patient with clinically significant corneal disease\n7. Patient with any evidence of severe or uncontrolled systemic diseases (e.g. active bleeding diatheses, active infection, or psychiatric illness) which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required for eligibility\n8. Evidence of spinal cord compression or brain metastases, defined as being clinically active and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Patients with clinically inactive or treated brain metastases who are asymptomatic (ie, without neurologic signs or symptoms and do not require treatment with corticosteroids or anticonvulsants) may be included in the study. Patients must have a stable neurologic status for at least 2 weeks prior to Cycle 1 Day 1\n9. Inadequate washout period prior to Cycle 1 Day 1, defined as:\n\n   1. Whole brain radiation therapy or stereotactic brain radiation therapy \\\u003C14 days\n   2. Previous treatment with T-DXd \\\u003C 28 days\n   3. Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study \\\u003C14 days or 5 half-lives, whichever is longer\n   4. Endocrine therapy \\\u003C21 days\n   5. Monoclonal antibodies \\\u003C28 days including immune checkpoint inhibitors (ICIs)\n   6. Major surgery (excluding placement of vascular access) \\\u003C28 days\n   7. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation \\\u003C28 days or palliative radiation therapy \\\u003C14 days\n   8. Live virus vaccination \\\u003C28 days\n10. Prior treatment with an anti-HER3 antibody\n11. Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade ≤1 or baseline, as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Patients with chronic Grade 2 toxicities (defined as no worsening to Grade \\>2 for at least 3 months prior to enrollment and managed with standard of care treatment) that the Investigator deems related to previous anticancer therapy, comprising the following, may be enrolled at the discretion of the Investigator:\n\n    * Chemotherapy-induced neuropathy\n    * Fatigue\n    * Residual toxicities from prior immuno-oncology treatment: Grade 1 or Grade 2 endocrinopathies provided they are clinically stable and receiving hormone replacement therapy when applicable which may include:\n\n      1. Hypothyroidism\u002F hyperthyroidism\n      2. Type I diabetes\n      3. Hyperglycemia\n      4. Adrenal insufficient\n      5. Adrenalitis\n      6. Skin hypopigmentation (vitiligo)\n12. Has known hypersensitivity to either the drug substances or the inactive ingredients of HER3-DXd and\u002For T-DXd\n13. Patient with a history of severe hypersensitivity reactions to other monoclonal antibodies or PARP inhibitors\n14. Has any malignancy other than locally advanced or ABC within 3 years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer or curatively treated in-situ disease or other curatively treated solid tumors\n15. Documented uncontrolled or significant cardiovascular disorder prior to Cycle 1 Day 1, including:\n\n    1. Corrected QT interval \\>450 ms according to Fridericia's formula (QTcF) based on triplicate 12-lead ECGs, approximately 1 minute apart\n    2. LVEF \\\u003C45% by either ECHO or MUGA or cardiac MRI if clinically indicated according to the investigator or consulting cardiologist\n    3. Resting systolic blood pressure \\>140 mmHg or diastolic blood pressure \\>90 mmHg\n    4. Myocardial infarction within 6 months\n    5. Symptomatic congestive heart failure (NYHA class from III to IV)\n    6. Uncontrolled angina pectoris within 6 months\n    7. Cardiac arrhythmia not controlled by ongoing antiarrhythmic treatment\n    8. Diagnosed or suspected long QT syndrome, or known family history of long QT syndrome\n    9. History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes\n    10. Patient has bradycardia of less than 50 bpm (as determined by central reading) unless the subject has a pacemaker\n    11. History of second or third degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers, and have no history of fainting or clinically relevant arrhythmia with pacemakers\n    12. Coronary\u002Fperipheral artery bypass graft within 6 months\n    13. Complete left bundle branch block\n16. Active Hepatitis B and\u002For Hepatitis C infection, such as those with serologic evidence of active viral infection within 28 days of Cycle 1, Day 1. Patients with past or resolved Hepatitis B virus (HBV) infection are eligible if:\n\n    1. Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive; OR\n    2. HBsAg positive and HBV deoxyribonucleic acid (DNA) viral load is documented to be ≤ 2000 IU\u002FmL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with normal transaminases (in the absence of liver metastasis); OR\n    3. HBsAg positive and HBV DNA viral load is documented to be ≤2000 IU\u002FmL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with liver metastasis and abnormal transaminases AST\u002FALT \\\u003C3 ULN For patients with HBsAg positive, if abnormal liver function is detected during study drug treatment, viral load should be tested to rule out reactivation.\n\n    Patients with a history of Hepatitis C infection will be eligible for enrollment only if the viral load according to local standards of detection, is documented to be below the level of detection in the absence of anti-viral therapy during the previous 12 weeks (ie, sustained viral response according to the local product label but not less than 12 weeks, whichever is longer)\n17. Female patient who is pregnant or breastfeeding or intends to become pregnant during the study\n18. Has a known human immunodeficiency virus (HIV) infection that is not well controlled. All the following criteria are required to define an HIV infection that is well controlled: undetectable viral ribonucleic acid (RNA) load, CD4+ counts\u002Flevels of \\>350 cells\u002FμL, no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the past 12 months, and stable for at least 3 weeks on same anti-HIV retroviral medications. If an HIV infection meets the above criteria, the patient's viral RNA load and CD4+ cell count should be monitored per local standard of care (eg, every 3 months). Patients with a well-controlled HIV infection may only be enrolled into Part 2 (dose expansion) of the study.\n19. Prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's judgment, could affect the safety of the patient; alter the absorption, distribution, metabolism or excretion of the study drug; or confound the assessment of study results\n20. Adult under legal protection: guardianship, curatorship, or legal protection; or patient deprived of his\u002Fher liberty by a judicial or administrative decision; or patient incapable of giving his\u002Fher consent, or patient under psychiatric care\n21. Participation in another clinical trial evaluating an experimental drug during the last 4 weeks (except non-interventional research) Specific exclusion criteria for each module\n\n    Module 0:\n\n    There are no specific exclusion criteria for module 0 (HER3-DXd monotherapy). Module 1 (olaparib)\n22. History of hypersensitivity to excipients of olaparib\n23. Inadequate washout period prior to Cycle 1 Day 1, defined as:\n\n    1. Strong CYP3A inhibitors \\\u003C 1 week\n    2. CYP3A inducers for olaparib and phenobarbital \\\u003C 5 weeks and for any other drug \\\u003C 3 weeks",{"count":328,"type":20},152,[51,23],"ICARUS-BREAST02 is an open-label, multicenter, phase 1b\u002F2, platform study that aims to evaluate the safety, tolerability, and efficacy of HER3-DXd monotherapy and in combination with other anti-cancer agents in patients with ABC.\n\nThe first 2 modules will evaluate: i. safety and efficacy of HER3-DXd with olaparib in patients with HER2-low and HER2-positive ABC progressed on T-DXd (Module 1) and HER3-DXd monotherapy in patients with HER2-low ABC progressed on T-DXd (Module 0).\n\nThe main objective of Part 1 is to assess the safety and tolerability of HER3-DXd monotherapy and combination and to determine the recommended phase 2 dose (RP2D) of the combination containing HER3-DXd.\n\nThe main objective of Part 2 is to assess the efficacy of study therapies in each module based on investigator assessment as evaluated by the objective response rate (ORR) at 6 months.",[183,26,245,56],"2024-03-28",{"date":334,"type":32},"2024-03-29",{"date":336,"type":32},"2024-03-21",{"date":338,"type":20},"2029-06",{"name":340,"class":39},"Gustave Roussy, Cancer Campus, Grand Paris",{"id":342,"slug":343,"hasResults":11,"nctId":344,"briefTitle":345,"officialTitle":346,"acronym":4,"eligibilityCriteria":347,"healthyVolunteers":11,"sex":99,"minAge":17,"maxAge":100,"enrollmentInfo":348,"targetDuration":4,"studyType":21,"phases":350,"briefSummary":352,"conditions":353,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":355,"lastUpdatePostDateStruct":356,"startDateStruct":358,"completionDateStruct":360,"leadSponsor":362,"locationsCount":120},"100537518","phase-3-disitamab-vedotin--pyrotinib-versus-thp-in-the-first-line-treatment-for-her2-advanced-breast-cancer-clinical-trial-100537518","NCT06278870","Disitamab Vedotin + Pyrotinib Versus THP in the First-line Treatment for HER2+ Advanced Breast Cancer Clinical Trial","Disitamab Vedotin in Combination With Pyrotinib Versus THP in the First-line Treatment for HER2-positive Advanced Breast Cancer, a Multicentre, Randomized, Double-blind Controlled, Phase III Trial","Inclusion Criteria:\n\n1. Adult female patients (age 18-75 years) with metastatic breast cancer confirmed by pathology or imaging;\n2. Pathologically confirmed HER2 positive (definition: Immunohistochemistry(IHC) 3+, or IHC 2+ and Fluorescent In Situ Hybridization(FISH) amplification);\n3. No previous chemotherapy regimen for metastatic breast cancer;\n4. At least one measurable lesion exists (Response Evaluation Criteria in Solid Tumors(RECIST) 1.1);\n5. Eastern Cooperative Oncology Group(ECOG) performance status score ≤ 2 and expected survival of not less than 3 months;\n6. Prior treatment-related toxicity at enrollment must have resolved to National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE) (version 5.0) ≤ 1 degree (except for alopecia or other toxicity that, in the judgment of the investigator, is not considered a risk to the safety of the patient);\n7. Patients with adequate organ function before enrollment:\n\n   1. White Blood Cell (WBC) ≥ 3.0 x 10\\^9\u002FL;\n   2. Neutrophil granulocyte (ANC) ≥1.5 x 10\\^9\u002FL;\n   3. Platelet (PLT) ≥70×10\\^9\u002FL;\n8. Liver, kidney, and cardiac function tests are essentially normal (based on the normal values in the laboratory of each study center):\n\n   1. Total bilirubin (TBIL) ≤ 3 x Upper Limit of Normal (ULN);\n   2. Alanine aminotransferase (ALT\u002FAST) ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver metastases);\n   3. serum creatinine ≤ 1.5 x ULN or creatinine clearance (Ccr) ≥ 60 ml\u002Fmin;\n9. . Normal cardiac function;\n\n   1. Left ventricular ejection fraction (LVEF) ≥ 55%;\n   2. QT-interval corrected with Fridericia (QTcF) ≤ 470ms;\n10. Hormone receptor status is clear;\n11. Female patients of childbearing potential who have a negative pregnancy test and agree to use an effective non-hormonal method of contraception during treatment and for at least 6 months after the last dose of the test drug;\n12. Able to understand the study process, voluntarily participate in this study, and sign an informed consent form.\n\nExclusion Criteria:\n\n1. Pathology suggestive of HER2 negativity (IHC 2+ and FISH-, or IHC 1+);\n2. Patients with known hypersensitivity to the active ingredient or other components of the study drug;\n3. Patients during pregnancy or lactation, patients with childbearing potential tested positive in a baseline pregnancy test, or patients unwilling to take effective contraceptive measures throughout the trial;\n4. Patients not eligible for this study judged by the investigator, a pre-existing disease or condition that may interfere with participation in the study or any serious medical disorder that may interfere with the safety of the subject (e.g., uncontrolled heart disease, high blood pressure, active or uncontrolled infections, active hepatitis B virus infection).",{"count":349,"type":20},312,[351],"PHASE3","The goal of this multicentre, randomized, double-blind controlled, phase III clinical trial is to compare the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab (THP) for newly diagnosed recurrent\u002Fmetastatic Human epidermal growth factor receptor 2 (HER2) positive advanced breast cancer, and to explore the impact of biomarkers on clinical efficacy and safety. The main questions it aims to answer are:\n\n* Analyse the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of THP.\n* Explore the impact of biomarkers on clinical efficacy and safety of the combination of disitamab vedotin in combination with pyrotinib treatment.\n\nParticipants in the experimental group will receive disitamab vedotin in combination with pyrotinib for 6-8 cycles (each cycle lasting 28 days), followed by maintenance treatment with trastuzumab in combination with pyrotinib. Participants in the control group will receive paclitaxel in combination with trastuzumab and pertuzumab for 6-8 cycles (each cycle lasting 21 days), followed by maintenance treatment with trastuzumab and pertuzumab.\n\nResearchers will compare disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab to see if disitamab vedotin in combination with pyrotinib could be a new option for first-line treatment of HER2-positive metastatic breast cancer.",[26,354],"First-line Treatment","2024-02-22",{"date":357,"type":32},"2024-02-26",{"date":359,"type":32},"2023-09-06",{"date":361,"type":20},"2031-06-30",{"name":363,"class":39},"Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University"]