[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"brca2-mutation\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:brca2-mutation":28},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,18,0,[8,48,72,102,127,167,199,262,287,316,360,391,413,457,480,508,539,563],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":31,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":36,"lastUpdatePostDateStruct":37,"startDateStruct":40,"completionDateStruct":42,"leadSponsor":44,"locationsCount":47},"100492635","phase-1-combination-therapy-in-cancers-with-mutations-in-dna-repair-genes-100492635",false,"NCT05694715","Combination Therapy in Cancers With Mutations in DNA Repair Genes","Combination Therapy of Niraparib and Irinotecan in Cancers With Mutations in DNA Repair Genes","Inclusion Criteria:\n\n1. Individuals 18 years of age or older.\n2. Ability to understand and willingness to voluntarily sign a written informed consent document prior to any study-related assessments or procedures are conducted; and willing and able to adhere to the study visit schedule and other protocol requirements.\n3. Solid tumors where topoisomerase I inhibitors have shown efficacy, including gastrointestinal tumors (e.g., colon, pancreatic, gastric cancer and cholangiocarcinoma), breast cancer, and ovarian cancer (prostate cancer is excluded), with one or more of the following DNA repair defects:\n\n   a. BRCA1, BRCA2, ATM, and\u002For PALB2 (based upon archival tumor tissue or germ line testing from any Clinical Laboratory Improvement Amendments (CLIA) approved lab). This testing must occur prior to study enrollment.\n4. Presence of at least one lesion with measurable disease as defined by RECIST 1.1 criteria for response assessment\n5. Advanced solid tumor malignancy without curative options\n6. At least 5 half-lives or 3 weeks (whichever is shorter) must have passed since last anticancer therapy\n7. The washout period for investigational agents without published half-lives should be 3 weeks since last therapy, and all treatment related toxicities must have recovered to less than grade 2.\n8. Eastern Cooperative Oncology Group (ECOG) Performance Status of \\\u003C=1 (Karnofsky \\> 60%; Appendix 1).\n9. Adequate organ function:\n\n   1. Absolute neutrophil count (ANC) \\>= 1.5 X 109\u002FL (no growth factors allowed within 14 days of enrollment)\n   2. Hemoglobin (Hgb) ≥10 g\u002FdL (no transfusion allowed within 7 days of enrollment)\n   3. Platelets (plt) \\>= 100 x 109\u002FL\n   4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \\\u003C=2.5 x Upper Limit Normal (ULN), or AST and ALT \\\u003C5 x ULN in patients with known liver metastases or known primary liver tumor(s)\n   5. Serum total bilirubin \\\u003C= 1.5 x ULN\n   6. Creatinine \\\u003C1.5 x ULN, or Estimated Glomerular filtration rate (GFR) \\>= 50ml\u002Fmin by Cockcroft-Gault (http:\u002F\u002Fwww.mdcalc.com\u002Fcreatinine-clearance-cockcroft-gault-equation\u002F)\n10. Must have recovered to less than Grade 2 (CTCAE v5.0) in terms of toxicity from prior treatments (excluding neuropathy which can be ≤ Grade 2, alopecia, nail changes\u002Fnail loss or other chronic minor grade 2 AEs).\n11. Must be able to take oral medications.\n12. Based on its mechanism of action and pre-clinical findings, irinotecan can cause fetal harm when administered to a pregnant woman. Additionally, the effects of niraparib on the developing fetus are unknown. Therefore:\n\n    a. Females of childbearing potential and their male partners are advised to practice a highly effective method of contraception during treatment with niraparib and\u002For irinotecan and for 180 days following the last dose for females and 90 days following the last dose for males. A woman is considered to be of childbearing potential unless one of the following applies:\n\n    i. Is considered to be permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.\n\n    ii. Is postmenopausal, defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 milli-international units per millilitre (mIU\u002FmL) or higher) may be used to confirm a postmenopausal 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 to confirm a postmenopausal state.\n\n    b. A male participant of reproductive potential is eligible to participate if he agrees to the following starting with the first dose of study treatment through at least 90 days (a spermatogenesis cycle) after the last dose of study treatment:\n\n    i. refrain from donating sperm.\n\n    ii. Must agree to use a male condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak).\n\n    c. Highly effective contraception is considered to be a method with a \\\u003C 1% per year failure rate. Recommendations for highly effective contraception while taking niraparib include:\n\n    i. Ongoing use of injectable or implantable progesterone.\n\n    ii. Placement of an intrauterine device or intrauterine system.\n\n    iii. Bilateral tubal occlusion.\n\n    iv. Complete (as opposed to periodic) abstinence\n\n    . v. Male sterilization, with appropriate post-vasectomy documentation of absence of sperm in ejaculate.\n13. Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.\n14. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n15. Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. For individuals with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n\nExclusion Criteria:\n\n1. Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he\u002Fshe were to participate in the study at clinician's discretion and not otherwise stated below.\n2. Prior allergic reaction to PARP inhibitor or irinotecan or their excipients. Prior PARP inhibitor or irinotecan (or topoisomerase 1 inhibitors) use is allowed.\n3. Individuals with known toxicity to irinotecan (e.g., grade 3 or 4 neutropenia) or suspected sensitivity.\n4. Individuals with homozygous or compound heterozygous UGT1A1 polymorphisms (e.g., alleles \\*28\u002F\\*28, \\*6\u002F\\*6, or \\*6\u002F\\*28) predicted to be associated with medium-to-high risk of irinotecan-related toxicity\n5. Individuals receiving any other investigational agents concurrently with the study drugs within 3 weeks or 5 half-lives, whichever is shorter, of the first dose of therapy preceding the study.\n6. Participants with unstable brain metastases are excluded. Patients with a history of brain metastases (\\>1cm) are permitted to enroll if they have been treated and have been stable for a minimum of one month on imaging. Patients may not currently receive steroids for their brain metastases. Patients with small, asymptomatic brain metastases (\\\u003C1cm) may enroll.\n7. Individuals with a second primary malignancy\n8. Individuals with a prior history of posterior reversible encephalopathy syndrome (PRES)\n9. Individuals with systolic blood pressure \\>140 mmHg or diastolic blood pressure \\>90 mmHg that has not been adequately treated or controlled\n10. History of a malabsorption syndrome or uncontrolled nausea, vomiting, or diarrhea that may interfere with the absorption of oral study medication in the opinion of the investigator.\n11. Known or suspected diagnosis of Myelodysplastic syndromes (MDS) or Acute myeloid leukemia (AML).\n12. Known Gilbert's disease\n13. Individuals who are pregnant and\u002For breast feeding, or expecting to conceive children while receiving study treatment and\u002For for up to 180 days after the last dose of study treatment.\n14. Inability to comply with study procedures or unwilling to use adequate highly effective contraception","ALL","18 Years",{"count":19,"type":20},24,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","The purpose of this phase 1 clinical trials is to determine whether niraparib (a Poly (ADP-ribose) polymerase inhibitor (PARPi)) can be safely combined with irinotecan with manageable toxicity and reasonable efficacy. Emerging evidence suggest that PARPi is an effective therapeutic strategy in a wider subset of solid tumors that may have defective homologous recombination (HR) or DNA repair gene mutations. BReast CAncer gene (BRCA), partner and localizer of BRCA2 (PALB2), and various other DNA repair germline mutations predispose carriers to cancers of the breast, ovaries, pancreas, prostate and melanoma. A number of preclinical studies have demonstrated that PARP inhibitors can work as chemopotentiators. There is significant interest in this combination, and the recommended phase II dose will be used in the upcoming NCI ComboMatch trial.",[26,27,28,29,30],"Metastatic Solid Tumor","BRCA1 Mutation","BRCA2 Mutation","ATM Gene Mutation","PALB2 Gene Mutation",[32,33,34],"DNA Repair Gene Mutations","Small Molecule Inhibitor","Poly (ADP-ribose) polymerase inhibitor therapy (PARPi)","RECRUITING","2026-06-16",{"date":38,"type":39},"2026-06-18","ACTUAL",{"date":41,"type":39},"2023-05-23",{"date":43,"type":20},"2028-01-31",{"name":45,"class":46},"University of California, San Francisco","OTHER",1,{"id":49,"slug":50,"hasResults":11,"nctId":51,"briefTitle":52,"officialTitle":53,"acronym":4,"eligibilityCriteria":54,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":55,"targetDuration":4,"studyType":21,"phases":56,"briefSummary":57,"conditions":58,"keywords":61,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":64,"lastUpdatePostDateStruct":65,"startDateStruct":67,"completionDateStruct":69,"leadSponsor":70,"locationsCount":47},"100529699","phase-1-olaparib-and-astx727-in-brca12--and-homologous-recombination-deficient-hrd-mutated-tumors-100529699","NCT06177171","Olaparib and ASTX727 in BRCA1\u002F2- and Homologous Recombination Deficient (HRD)-Mutated Tumors","A Phase I\u002FIb Study of Olaparib and ASTX727 in BRCA1\u002F2- and HRD-mutated Tumors","Inclusion Criteria:\n\n1. Participants must have histologically or cytologically confirmed advanced solid tumors (any solid tumor type) with:\n\n   Phase I, Dose Escalation: Germline and\u002For somatic mutation\\* in one or more of the following genes: BRCA1, BRCA2, PALB2, ATM, and\u002For CHEK2.\n\n   Phase Ib, Dose Expansion\\*\\*:\n   1. Expansion Cohort A (n=6): Germline mutation\\* (with or without accompanying somatic mutation) in one or more of the following genes: BRCA1, BRCA2, PALB2, ATM, and\u002For CHEK2;\n   2. Expansion Cohort B (n=6): Germline and\u002For somatic mutation\\* in one or more of the following genes: BRCA1, BRCA2, PALB2, ATM, and\u002For CHEK2.\n\n      * Testing for DNA repair mutations should occur prior to study consent or enrollment via a CLIA-approved test.\n2. Has measurable disease per RECIST 1.1 as assessed by the investigator. Lesions situated in previously irradiated areas are considered measurable if progression has been demonstrated in such lesions.\n3. Participants may have received any lines of prior therapy and is refractory or intolerant to therapy approved for their condition or unwilling to receive currently approved therapy.\n4. Prior PARP inhibitors are allowed, provided the following two criteria are met:\n\n   1. Participant has NOT required toxicity related dose reductions or dose delays during prior PARP inhibitor treatment; and\n   2. Participant has NOT experienced any allergic reaction to PARP inhibitors.\n5. Age \\>=18 years\n6. Eastern Cooperative Oncology Group (ECOG) performance status \\\u003C2, or Karnofsky \\>60%\n7. Demonstrates adequate organ function as defined below:\n\n   Adequate bone marrow function:\n   1. hemoglobin \\>=10.0 g\u002Fdl\n   2. absolute neutrophil count \\>=1,500\u002Fmicroliter (mcL)\n   3. platelets \\>=100,000\u002FmcL\n\n   Adequate hepatic function:\n   1. total bilirubin ≤ 1.5 x institutional upper limit normal (ULN)\n   2. aspartate aminotransferase (AST)\u002F(SGOT) \\\u003C= 2.5 x institutional ULN\n   3. alanine aminotransferase (ALT)\u002F(SGPT) \\\u003C= 2.5 x institutional ULN\n   4. creatinine \\\u003C= 1.5 x institutional ULN or creatinine clearance Glomerular filtration rate (GFR) \\>= 50 mL\u002Fmin\u002F1.73 m\\^2, calculated using the Cockcroft-Gault equation.\n8. Ability to understand and the willingness to sign a written informed consent document.\n9. Human immunodeficiency virus (HIV)-infected individuals on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial.\n10. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n11. Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. Individuals with HCV infection who are currently on treatment could be eligible if HCV viral load is undetectable.\n12. Individuals with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for at least 4 weeks. Participants need to be without requirement for steroid treatment for at least 14 days prior to the first dose of study intervention. A participant with one or two lesions that have been definitely treated with resection or focal radiation and has no symptoms is eligible after 2 weeks.\n13. Based on findings from human data and\u002For animal studies, and their mechanisms of action, ASTX727 and olaparib can cause fetal harm when administered to a pregnant woman. For this reason, females of child-bearing potential (defined below) must agree to use adequate contraception including hormonal or barrier methods or strict abstinence for the duration of study treatment and for 6 months after last administration of study treatment. Males (with female partners of reproductive potential or who are pregnant) treated or enrolled on this protocol also must agree to use adequate contraception for the duration of study treatment, and for 3 months after last administration of study treatment. Should an individual participating in this study (or the partner of an individual participating in the study) become pregnant or suspect pregnancy, they should inform the treating physician immediately. A female is considered to be of childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice), unless it is documented that the individual meets either of the following two criteria: (1) has reached a postmenopausal state (\\>= 12 continuous months of amenorrhea with no identified cause other than menopause); or (2) has undergone surgical sterilization (i.e., hysterectomy and\u002For bilateral oophorectomy for removal of uterus and\u002For ovaries).\n14. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.\n\nNote: Diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) are excluded per Exclusion # 7.\n\nExclusion Criteria:\n\n1. Has received systemic anticancer therapies within 3 weeks of first dose, radiation within 2 weeks, antibody therapy within 4 weeks. Concomitant administration of Luteinizing hormone-releasing hormone (LHRH) analogues for prostate cancer and somatostatin analogues for neuroendocrine tumors are allowed as per standard of care.\n2. Has not recovered from adverse events due to prior anti-cancer therapy to \\\u003C= grade 1 (CTCAE v5.0) or baseline (other than alopecia).\n3. Receipt of any other investigational agents or devices within 3 weeks prior to initiation of trial therapy.\n4. Unable to swallow oral medications\n5. Individuals who are breast-feeding\u002Fchest-feeding (because of the potential for serious adverse reactions in breastfeed infants from olaparib and ASTX727). Study participants who are lactating must agree to discontinue breast-feeding\u002Fchest-feeding for the duration of study treatment and for 1 month after the final dose of trial therapy.\n6. Individuals who are pregnant (because of the potential for olaparib and ASTX727 to cause serious adverse reactions to the unborn child). Females of childbearing potential (defined below) must have a negative urine or serum pregnancy test within 72 hours prior to first administration of study drug. A female is considered to be of childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice), unless it is documented that the individual meets either of the following two criteria: (1) has reached a postmenopausal state (\\>= 12 continuous months of amenorrhea with no identified cause other than menopause); or (2) has undergone surgical sterilization (i.e., hysterectomy and\u002For bilateral oophorectomy for removal of uterus and\u002For ovaries). Individuals with any condition or social circumstance that, in the opinion of the investigator, would impair the participant's ability to comply with study activities, interfere with participant safety, or study endpoints.\n7. Diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).\n8. Taking a prohibited medication that cannot be safely discontinued or substituted.",{"count":5,"type":20},[23],"This is a single center, phase I\u002FIb clinical trial evaluating the combination of the poly adenosine diphosphate-ribose polymerase (PARP) inhibitor olaparib with the DNA methyltransferase (DNMT) inhibitor ASTX727, which is an oral formulation of decitabine with cedazuridine (a cytidine deaminase inhibitor that allows for oral administration). The study population consists of adults with advanced\u002Fmetastatic solid tumor malignancies with germline or somatic mutations in the HRR pathway (i.e., BReast CAncer gene 1 (BRCA1), BReast CAncer gene 2(BRCA2), Partner And Localizer of BRCA2 (PALB2), ATM, and\u002For Checkpoint kinase 2 (CHEK2) mutations).",[27,28,59,30,60,29],"BRCA Mutation","Checkpoint Kinase 2 Gene Mutation",[62,63],"Homologous Recombination Deficiency","HRR Pathway","2026-05-22",{"date":66,"type":39},"2026-05-27",{"date":68,"type":39},"2024-02-07",{"date":43,"type":20},{"name":71,"class":46},"Varun Monga, MBBS",{"id":73,"slug":74,"hasResults":11,"nctId":75,"briefTitle":76,"officialTitle":76,"acronym":77,"eligibilityCriteria":78,"healthyVolunteers":11,"sex":79,"minAge":17,"maxAge":4,"enrollmentInfo":80,"targetDuration":4,"studyType":21,"phases":82,"briefSummary":84,"conditions":85,"keywords":88,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":93,"lastUpdatePostDateStruct":94,"startDateStruct":96,"completionDateStruct":98,"leadSponsor":100,"locationsCount":47},"100578930","cognitive-behavioral-therapy-for-fear-of-cancer-recurrence-in-women-with-brca12-gene-100578930","NCT06817694","Cognitive Behavioral Therapy for Fear of Cancer Recurrence in Women With BRCA1\u002F2 Gene","CBT-FCRBRCA1\u002F2","Inclusion Criteria:\n\n* 1\\) Have completed primary treatment for breast or ovarian cancer (i.e., surgery, chemotherapy, and radiotherapy).\n* 2\\) Be known to carry a BRCA1\u002F2 pathogenic mutation.\n* 3\\) Have a clinical level of fear of cancer recurrence as defined by a score of 13 or more on the Fear of Cancer Recurrence Inventory severity subscale.\n* 4\\) Be at least 18 years of age.\n* 5\\) Be able to read, understand and express herself in French.\n\nExclusion Criteria:\n\n* 1\\) Have distant metastases (in the case of ovarian cancer, only stages IV and IIIC will be excluded).\n* 2\\) Be known to carry a BRCA1\u002F2 \"VUS\" mutation.\n* 3\\) Have a known cognitive disorder.\n* 4\\) Have a known severe psychological disorder (e.g., psychotic disorder, bipolar disorder, substance abuse or dependence disorder).\n* 5\\) Have already taken part in the original FCR group psychotherapy at the CHU de Québec.\n* 6\\) Women taking psychotropic medication are eligible, but only if the dosage has been stable for at least one month.","FEMALE",{"count":81,"type":20},250,[83],"NA","The goal of this clinical trial is to determine whether an adapted version of a current cognitive-behavioural group therapy (CBT) protocol for cancer survivors to the specific needs of women who are carriers of the BRCA1\u002F2 genetic mutation will reduce their levels of fear of cancer recurrence. The main questions this study aims to answer are:\n\n* Will the women who have received the adapted CBT be satisfied with it?\n* Will there be a significant difference in the women's fear of cancer recurrence and other variables (e.g., depression, anxiety, insomnia, fatigue, quality of life) between the comparison groups?\n* Will the effects of the adapted CBT hold over time?\n* What are the roles of different etiological mediating variables in the relationship between fear of cancer recurrence and the effects of the adapted CBT on the severity of fear of cancer recurrence?\n\nResearchers will compare the effects of the adapted CBT between the immediate condition and the waitlist condition.\n\nParticipants will be:\n\n* Either placed in the immediate condition or the waitlist condition (the participants in the waitlist condition will begin their therapy once the immediate group is done with theirs).\n* Taking part in a group CBT session online once a week for eleven weeks.\n* Completing questionnaires pre-intervention, post-intervention, 3 months post-intervention, and 6 months post-intervention.",[86,28,87],"Breast Cancer Susceptibility Gene (BRCA1) Mutation","Fear of Cancer Recurrence",[27,89,90,91,92],"BRCA 2 Mutation","Fear of cancer recurrence","Cognitive-Behavioral Therapy","Cancer","2026-03-26",{"date":95,"type":39},"2026-03-31",{"date":97,"type":20},"2026-02",{"date":99,"type":20},"2028-12",{"name":101,"class":46},"CHU de Quebec-Universite Laval",{"id":103,"slug":104,"hasResults":11,"nctId":105,"briefTitle":106,"officialTitle":107,"acronym":108,"eligibilityCriteria":109,"healthyVolunteers":11,"sex":79,"minAge":110,"maxAge":111,"enrollmentInfo":112,"targetDuration":4,"studyType":21,"phases":114,"briefSummary":115,"conditions":116,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":117,"lastUpdatePostDateStruct":118,"startDateStruct":120,"completionDateStruct":122,"leadSponsor":124,"locationsCount":126},"100590845","hormone-replacement-therapy-after-risk-reducing-salpingo-oophorectomy-100590845","NCT06972719","Hormone Replacement Therapy After Risk Reducing Salpingo-oophorectomy","Patient Centered Education About Hormone Replacement Therapy After Risk Reducing Salpingo-oophorectomy: a Pilot Randomized Controlled Trial","BRCA HRT Pilot","Inclusion Criteria:\n\n* BRCA1 or BRCA2 germline mutation\n* scheduled for a risk-reducing salpingo-oophorectomy (RRSO) by Duke Gynecologic Oncologist\n* premenopausal\n\nExclusion Criteria:\n\n* personal history of cancer\n* postmenopausal\n* \\>50 years old\n* unable to provide informed consent in English","19 Years","50 Years",{"count":113,"type":20},50,[83],"The goal of this study is to develop an educational aid about hormone replacement therapy that physicians can share with patients as part of their pre-surgical counseling for a risk-reducing salpingo-oophorectomy (RRSO).",[27,28],"2026-03-25",{"date":119,"type":39},"2026-03-27",{"date":121,"type":39},"2025-09-30",{"date":123,"type":20},"2026-12-31",{"name":125,"class":46},"Duke University",2,{"id":128,"slug":129,"hasResults":11,"nctId":130,"briefTitle":131,"officialTitle":132,"acronym":133,"eligibilityCriteria":134,"healthyVolunteers":11,"sex":79,"minAge":4,"maxAge":4,"enrollmentInfo":135,"targetDuration":4,"studyType":21,"phases":137,"briefSummary":139,"conditions":140,"keywords":147,"overallStatus":157,"whyStopped":4,"lastUpdateSubmitDate":158,"lastUpdatePostDateStruct":159,"startDateStruct":161,"completionDateStruct":163,"leadSponsor":165,"locationsCount":126},"100631386","phase-2-randomized-double-blind-phase-ii-trial-of-baby-exemestane-versus-baby-tamoxifen-in-post-menopausal-women-at-high-risk-for-breast-cancer-100631386","NCT07499999","Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer","Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer (BabyTEARS)","BabyTEARS","Inclusion Criteria:\n\n* Postmenopausal state is defined⁸ as no menses for 12 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.\n* Any of the following criteria must be met:\n\n  * Recent (within 12 months from date of consent form signature) histologic diagnosis of ER+ve (\\>5%) DCIS (patients with DCIS should have undergone breast-conserving therapy i.e. lumpectomy to remove the tumor with negative surgical margins followed by radiotherapy (see footnote 1 below)) diagnosis within 3 years of HRL (ADH, LCIS, ALH), or;\n  * At least 3% breast cancer risk at 5 years (or 5% risk at 10yrs) per one of the following risk models: the Breast Cancer Surveillance Consortium risk calculator V3 or Tyrer-Cuzick model V8 or;\n  * Known carriers of a germline pathogenic\u002Flikely pathogenetic variant in the following moderate penetrance genes (CHEK2 or ATM), or women with chest wall irradiation before age of 30 years\n* Eastern Cooperative Oncology Group - Performance Status (ECOG-PS) 0-1\n* Able to swallow oral medications\n* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Specifically, all cancers diagnosed since 3 years or longer except for breast and endometrial are eligible.\n* Ability to understand and the willingness to sign a written informed consent document\n* Mammography performed up to 6 months before the trial consent form signature\n* DEXA performed up to 12 months before the trial consent form signature\n* Life expectancy ≥ 10 years\n* Normal liver function tests and blood cell count\n* Negative gynecological examination performed up to 6 months before the trial consent form signature.\n\nᶥ While DCIS and ADH are routinely excised, and treatment of DCIS often includes radiotherapy, lobular neoplasia (ALH and classic LCIS) are not routinely excised in most US centers unless radiologic-pathologic findings are discordant given the very low risk of an associated cancer.11,12 Participants with DCIS should have undergone breast-conserving therapy i.e. lumpectomy to remove the tumor with negative surgical margins followed by radiotherapy. All DCIS will require excision to clear margins per the SSO\u002FASCO\u002FASTRO margin guidelines for DCIS.88 In selected cases, the decision to omit RT might be taken according to low risk clinical-pathological factors (e.g., age\\>70, low grade, size \\\u003C 1 cm, and genomic assays if available) as well as patient preference after full discussion of the risks and benefits.\n\nExclusion Criteria:\n\n* Pre\u002Fperimenopausal women: exemestane is only effective in post-menopausal women\n* History of DVT or PE: tamoxifen can increase tendency to blood clot\n* Endometrial cancer: full-dose tamoxifen is associated with increased risk of endometrial cancers\n* Macular disorders: tamoxifen is associated with retinal damage\n* Inability to comply with study procedures: standard\n* Prior use of antiestrogens within 12 months from the date of the trial consent form signature: there can be long duration effects from antiestrogens that could influence trial drug effects\n* Use of hormone replacement therapy (HRT) within 3 months from the date of the trial consent form signature: similarly, wish to avoid any long lasting effect before alternate effect from study drugs\n* Severe osteoporosis (T score ≤ 2.5 at either spine or hip), or recent vertebral fracture (within 6 months) not treated with zoledronic acid or denosumab: Exemestane is an aromatase inhibitor which can worsen bone loss (osteoporosis)\n* Current use of terbinafine, quinidine, cinacalcet, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort, warfarin, erythromycin, cyclosporin, nifedipine and any concomitant coumarin-type anti-coagulant therapy: these drugs compete for the Cytochrome P450 metabolic pathways of tamoxifen and exemestane\n* Moderate or severe renal impairment: Exemestane is eliminated equally by liver and renal metabolism\n* Known hypersensitivity to study drugs: standard\n\nScreening Eligibility Criteria\n\nTo register a participant to the screening phase, the following documents should be provided by the participating site:\n\nSigned participant consent form\n\n* Postmenopausal status, and any of the following:\n\n  * Histological report of ER-positive DCIS within 12 months, or HRL of the breast within 3 years from date of consent form signature, or;\n  * Report of risk assessment ≥3% in 5 years or 5% in 10 years of breast cancer according to the selected risk model(s) different criteria within 6 months from screening, or;\n  * Documentation of women carriers of a germline pathogenic\u002Flikely pathogenetic variant in a moderate penetrance gene (CHEK2 or ATM), or;\n  * Documented history of chest wall radiotherapy before age 30.\n* Inclusion of Women and Minorities\n\nOnly women will be recruited in the study given that breast cancer is much more frequent in women than men and because exemestane is contraindicated in men because of risk of uncontrolled gonadal stimulation. Women of all races and ethnic groups are eligible for this trial. At participating sites, efforts will be made to enroll women from diverse ethnic and socio-economic backgrounds, including recruitment of non-white women in a selected New York city area.\n\nNIH policy requires that women and members of minority groups and their subpopulations be included in all NIH-supported biomedical and behavioral research projects involving NIH-defined clinical research unless a clear and compelling rationale and justification establishes to the satisfaction of the funding Institute \\& Center (IC) Director that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. Exclusion under other circumstances designated by the Director, NIH, upon the recommendation of an IC Director based on a compelling rationale and justification. Cost is not an acceptable reason for exclusion except when the study would duplicate data from other sources. Women of childbearing potential should not be routinely excluded from participation in clinical research.",{"count":136,"type":20},140,[138],"PHASE2","The goal of this research study is to evaluate the efficacy and safety of low-dose exemestane versus low-dose tamoxifen in post-menopausal women at high risk for breast cancer.\n\nThe names of the study drugs involved in this study are:\n\n* Exemestane (a type of steroidal aromatase inhibitor)\n* Tamoxifen (a type of selective estrogen receptor modulator)",[141,142,143,144,28,145,146],"Breast Cancer","Ductal Carcinoma","Estrogen-receptor-positive Breast Cancer","Atypical Lobular Hyperplasia","CHEK2 Gene Mutation","Ataxia Telangiectasia Mutated Gene Mutation",[141,148,149,150,151,152,153,144,154,155,156],"High Risk Breast Cancer","Cancer Prevention","Ductual Carcinoma in Site","Estrogen Receptor Positive","High Risk Lesions","HRL","BRCA2","CHEK2","ATM","NOT_YET_RECRUITING","2026-03-24",{"date":160,"type":39},"2026-03-30",{"date":162,"type":20},"2026-09-09",{"date":164,"type":20},"2028-08-31",{"name":166,"class":46},"Dana-Farber Cancer Institute",{"id":168,"slug":169,"hasResults":11,"nctId":170,"briefTitle":171,"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":188,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":158,"lastUpdatePostDateStruct":190,"startDateStruct":191,"completionDateStruct":193,"leadSponsor":195,"locationsCount":198},"100546483","phase-1-a-study-of-parg-inhibitor-etx-19477-in-patients-with-advanced-solid-malignancies-100546483","NCT06395519","A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies","ERADIC8","Inclusion Criteria:\n\n* Males and females of age ≥ 18 years at the time of signing the informed consent document.\n* Histologically or cytologically confirmed advanced (incurable recurrent, unresectable, or metastatic) solid cancer, excluding primary central nervous system (CNS) tumors.\n* Any solid tumor malignancy, excluding primary CNS tumors, with progression on or after or intolerance to most recent systemic therapy. Preferential enrollment consideration will be made for patients with known BRCA2 mutations resulting in loss of function.\n* Measurable disease per RECIST v1.1.\n* ECOG performance status 0-1.\n* Progression on or after or intolerance to most recent systemic therapy. Prior treatment in the recurrent\u002Fmetastatic setting; patients must have received approved standard therapy that is available to the patient that is known to confer clinical benefit, unless this therapy is contraindicated, intolerable to the patient, or is declined by the patient.\n* No investigational agent within 3 weeks or 5 half-lives (whichever is shorter; minimum of 2 weeks) prior to first dose of study drug.\n* Life expectancy of at least 3 months.\n\nExclusion Criteria:\n\n* Receiving continuous corticosteroids at prednisone-equivalent dose of \\>10 mg\u002Fday. Chronic systemic corticosteroid therapy for physiologic replacement (≤10 mg\u002Fday of prednisone equivalents) and the use of non-systemic corticosteroids (e.g., inhaled, topical, intra-nasal, intra-articular, or ophthalmic) are permitted.\n* Definitive radiotherapy within 6 weeks and palliative radiation within 2 weeks prior to the first dose of study drug.\n* Symptomatic untreated or progressing brain metastases. Stable, treated brain metastases are allowed if no evidence of radiologic or clinical progression or increasing corticosteroid use for at least 4 weeks.\n* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ETX-19477 and no history of bowel obstruction within 6 months and\u002For peritoneal fluid drainage within 8 weeks prior to the first dose of study drug.\n* Known symptomatic and radiologically progressing or leptomeningeal disease (LMD). If LMD has been reported radiographically on baseline magnetic resonance imaging (MRI), but is not suspected clinically by the Investigator, the patient must be free of neurological symptoms of LMD.\n* Resting ECG with QT interval calculated using the Fridericia's formula (QTcF) \\>470 msec on 2 or more timepoints within a 24-hour period, or history or family history of congenital long QT syndrome, or taking concomitant medications that are known to prolong the QT\u002FQTc interval, or history of additional risk factors for torsades de pointes (Tdp).\n* History of myocardial infarction or unstable angina within 6 months prior to enrollment, or clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension, clinically significant uncontrolled arrhythmias, or any history of symptomatic congestive heart failure.\n* Known active or chronic infection (viral, bacterial, or fungal), including tuberculosis, hepatitis B, hepatitis C, or AIDS-related illness. Controlled infections, including HIV and \"cured\" hepatitis C (no active fever, no evidence of systemic inflammatory response syndrome) that are stable with undetectable viral load on antiviral treatment are not exclusionary.\n* Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (with exception of patients with Gilbert's Syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per Investigator assessment).\n* Known other previous\u002Fcurrent malignancy requiring treatment within ≤2 years except for limited disease treated with curative intent, such as carcinoma in situ, squamous or basal cell skin carcinoma, or superficial bladder carcinoma and not requiring ongoing chemotherapy.\n* Patients receiving proton pump inhibitors (PPIs), strong cytochrome P450 (CYP)3A inhibitors and inducers, or P-glycoprotein (P-gp) inhibitors. Patients should not receive PPIs within 7 days prior to first dose of study drug. Strong CYP3A inducers or inhibitors or strong P-gp inhibitors should not be given within 6 half-lives prior to first dose of study drug.\n* Patients currently treated with therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants",{"count":175,"type":20},120,[23,138],"This is a two-part, open-label, multicenter, dose escalation and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and anti- tumor activity of ETX-19477, a novel reversible small molecule inhibitor of PARG.",[179,141,180,181,182,28,183,184,27,59,185,186,187],"Advanced or Metastatic Solid Tumors","Ovarian Cancer","Prostate Cancer","Epithelial Ovarian Cancer","ER+ Breast Cancer","Castrate Resistant Prostate Cancer","Endometrial Cancer","Colorectal Cancer","Gastric Cancer",[189],"PARG Inhibitor",{"date":119,"type":39},{"date":192,"type":39},"2024-05-13",{"date":194,"type":20},"2026-12",{"name":196,"class":197},"858 Therapeutics, Inc.","INDUSTRY",14,{"id":200,"slug":201,"hasResults":11,"nctId":202,"briefTitle":203,"officialTitle":204,"acronym":205,"eligibilityCriteria":206,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":207,"targetDuration":4,"studyType":21,"phases":208,"briefSummary":209,"conditions":210,"keywords":228,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":254,"lastUpdatePostDateStruct":255,"startDateStruct":257,"completionDateStruct":259,"leadSponsor":260,"locationsCount":126},"100374021","phase-1-sharon-a-clinical-trial-for-metastatic-cancer-using-chemotherapy-and-patients-own-stem-cells-100374021","NCT04150042","SHARON: A Clinical Trial for Metastatic Cancer Using Chemotherapy and Patients' Own Stem Cells","SHARON: Study of Metastatic Cancers in Patients Using Autologous Stems Cells and Potentiated Redox Cycling to Overcome Drug Resistance to Nitrogen Mustard Derivatives","SHARON","Inclusion Criteria\n\n* Age ≥ 18 years.\n* Pancreatic or breast cancer, as described below.\n* Stage IV (based on AJCC staging guidelines) at the time of enrollment.\n\n  a. Note that potential subjects with stage IV cancer that have had a complete response from prior chemotherapy are still potentially eligible.\n* Expected survival time ≥ 6 months, as determined by the investigator.\n* Life expectancy not severely limited by diseases other than malignancy, as determined by the investigator.\n* Karnofsky score ≥ 60%.\n* No chemotherapy within 2 weeks of enrollment.\n* Prior surgical resection or ablation of the primary tumor is allowed but not required.\n* If post-surgical, the subject must be at least 28 days post-op with the surgical wounds healed and significant complications resolved.\n* Potential subjects who have received previous chemotherapy and\u002For PARP inhibitors may be enrolled.\n* Measurable or non-measurable disease by the revised response evaluation criteria in solid tumors (RECIST) v.1.1.\n* For potential subjects with a germline BRCA1, BRCA2, or PALB2 mutation:\n\n  a. The mutation must be known to be deleterious or suspected to cause functional impairment as assessed by a CLIA-certified laboratory according to the variant classification criteria described in the study protocol.\n* For potential subjects with somatic BRCA1, BRCA2, or PALB2 mutations:\n\n  1. The mutation must be a known or suspected deleterious mutation as assessed by a CLIA-certified laboratory according to the variant classification criteria described in the study protocol.\n  2. There must be biallelic loss or inactivation of the mutated BRCA1, BRCA2, or PALB2 gene as assessed by a CLIA-certified laboratory.\n  3. The Genetics Review Committee for this trial, which is comprised of a core group of investigators and whose actions are performed in accordance with the committee's charter, must agree that the biallelic mutations are deleterious or suspected deleterious.\n* For subjects without a BRCA1, BRCA2, or PALB2 mutation\n\n  1. Subject must have received at least 16 weeks of first-line (platinum-based\\*) chemotherapy with no evidence of treatment failure, where treatment failure is defined as growing tumors, new lesions, or a steadily rising tumor marker during or within eight weeks of completion of the first line therapy.\n  2. \\* Subjects can also have been treated with FOLFIRINOX but switched to FOLFIRI due to oxaliplatin side effects.\n* For potential subjects with pancreatic cancer:\n\n  1. Pancreatic ductal adenocarcinoma or pancreatic acinar cell carcinoma.\n  2. If the potential subject has had surgical resection of the primary tumor, then there must be no evidence of disease progression between the time of surgical resection of the primary tumor and screening for enrollment if the patient is seeking enrollment in the immediate post-surgery period.\n* For potential subjects with breast cancer:\n\n  1. Adenocarcinoma of the breast.\n  2. HER2-negative cancer as per American Society of Clinical Oncology\u002FCollege of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guidelines.\n  3. Male or female sex.\n* Histological or cytological confirmation of the primary cancer diagnosis is required.\n* Metastatic disease must be histologically or cytologically confirmed unless in the clinical judgment of the investigator a biopsy is not needed for diagnostic purposes.\n* Female participants of childbearing potential must agree to do one of the following from the time of signing of the informed consent through 6 months after the last dose of melphalan:\n\n  1. Simultaneously practice two effective barrier methods of contraception. Oral and injectable contraceptives are not allowed. Barrier methods of birth control (e.g., diaphragm and spermicide, or condom and spermicide) are required.\n  2. Practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods, and withdrawal) are not acceptable methods of contraception.\n* Male participants:\n\n  1. Unless the male is in a monogamous relationship with a female that does not have child-bearing potential, male subjects (even if surgically sterilized) must agree to do one of the following from the time of signing of the informed consent through 6 months after the last dose of melphalan:\n\n     1. Practice effective barrier contraception, plus a second method of effective contraception.\n     2. Practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods, and withdrawal) are not acceptable methods of contraception.\n\nExclusion Criteria\n\n* Rapid disease progression or clinical features concerning for onset of rapid symptomatic deterioration, as determined by the investigator.\n* Biliary tract obstruction.\n* Current cholangitis. A biliary stent in situ does not otherwise exclude protocol participation.\n* A history of only one episode of cholangitis and fewer than 30 days have passed since discontinuation of antibiotic treatment.\n* A history of multiple episodes of cholangitis and after discussion between the site study team and sponsor medical monitor and careful evaluation for suitability the patient is deemed to be unsuitable for the trial due to risk of recurring cholangitis.\n* Portal hypertension.\n* Sinistral portal hypertension.\n* Obliteration or significant obstruction of the major veins or arteries (e.g., portal vein, superior mesenteric artery, superior mesenteric vein).\n* Clinically significant malignant ascites or malignant pleural effusion, as determined by the investigator.\n* Metastatic lesion to the heart or eye.\n* Chemotherapy for an indication other than treatment of the current cancer within the past 1 year with a more than 30% risk of recurrence as determined by the investigator.\n* Known or suspected metastatic involvement of the central nervous system.\n* Left ventricular ejection fraction less than 45% by Multigated Acquisition Scan or echocardiogram (or significantly below the lower limit of normal for the specific test).\n* Clinically significant structural heart disease or vascular disease.\n* Myocardial infarction within 6 months prior to enrollment; New York Heart Association (NYHA) Class III or IV heart failure; angina; uncontrolled ventricular arrhythmias; or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.\n* Clinically significant prolongation of QTc (Bazett formula) on EKG, defined as \\> 0.45 s in males and \\> 0.47 s in females.\n* Severe hypertension, which is defined as the presence of any of the following:\n\n  1. History of hypertensive crisis, hypertensive emergency, or malignant hypertension within the last year.\n  2. Sustained or persistent systolic BP \\> 165 mm Hg or diastolic \\> 110 mm Hg.\n* Other clinically significant cardiovascular disease.\n* NOTE:\n\n  1. A past history of severe hypertension that is well-controlled with therapy or that was addressed by removal of the cause (e.g., removal of a medicine that caused the severe hypertension) is not an exclusion criterion.\n  2. The presence of a pacemaker is not a contraindication and is not considered an exclusion criterion\n* History or evidence of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis).\n* If a smoker, refusal to stop smoking for the duration of the trial.\n* FEV1 or DLCO (adjusted for hemoglobin) \\\u003C 50% of predicted.\n* Total bilirubin \\> 2x upper normal limit, except that potential subjects with Gilbert's Disease are permitted to exceed 2x upper normal limit.\n* ALT or AST \\> 2.5x upper normal limit.\n* Alkaline phosphatase \\> 2.5x upper normal limit, in conjunction with elevated GGT.\n* Albumin \\\u003C 3.0 g\u002Fdl.\n* Clinical evidence of sinusoidal obstruction syndrome.\n* Corrected creatinine clearance consistently \\\u003C 50 ml\u002Fmin\u002F1.73 m\\^2.\n* Clinically significant renal disease.\n* Hemolytic anemia.\n* Family history of catalase deficiency or history or evidence of a severe adverse reaction to hydrogen peroxide consistent with catalase deficiency, unless testing has demonstrated that the patient is not catalase-deficient.\n* Evidence of bone marrow insufficiency or failure, in the judgment of the investigator.\n* A hemoglobin \\\u003C 9 g\u002FdL.\n* G6PD deficiency as measured by quantitative enzyme levels below the normal reference range in blood.\n* Pre-existing bleeding diathesis or coagulopathy.\n* Potential subject is pregnant.\n* Breast feeding and unwilling to stop.\n* Wilson's disease.\n* Primary or secondary hemochromatosis.\n* Hgb A1c \\> 9%.\n* Hyperuricemia that is not responsive to therapy.\n* Plasma oxalate greater than 10 µM, which is not responsive to measures to reduce the level below 10 µM.\n* History of clinically significant elevation of plasma oxalic acid or complications related to oxalic acid.\n* Prior or current hepatitis B or C.\n* HIV infection or seropositivity for HIV.\n* Active, clinically significant bacterial, viral, or fungal infection.\n* History of colonization with a multidrug-resistant \"superbug\" that poses a high risk of an untreatable infection in the setting of neutropenia.\n* Uncontrolled seizure disorder.\n* If a potential subject has received radiation, then any of the following:\n\n  1. A volume ≥ 700 ml of normal liver received a dose ≥ 10 Gy.\n  2. The mean dose to normal liver (i.e., liver minus gross tumor volume) was ≥ 10 Gy.\n  3. The mean dose to normal lung (i.e., lung minus gross tumor volume) was ≥ 4 Gy.\n* History of significant allergy or other contraindication to BCNU, melphalan, vitamin B12b, vitamin C, pegfilgrastim, or Neupogen, or to any excipient in those drugs.\n* Use of any of the following cytochrome P450 2b6 (CYP2b6) inducers within 21 days of the planned date of BCNU treatment: phenobarbital, carbamazepam, rifampicin, phenytoin, sulfinpyrazone, or verapamil.\n* Disulfiram (Antabuse) use within 30 days of the planned ethanol administration.\n* Current chronic use of immunosuppressive agents (e.g., methotrexate, cyclosporine, corticosteroids).\n* Prior bone marrow stem cell transplant.\n* Except for adjuvant therapy for breast cancer or pancreatic cancer, prior radiation therapy to the brain, kidneys, pelvis, or GI tract or treatment with yttrium-90.\n* Prior treatment with bleomycin or BCNU.\n* Prior treatment, within 30 days of enrollment, with a drug that has not been FDA-approved for any indication (cancer or otherwise).\n* Subject has not fully recovered (i.e., there remain toxicities \\> Grade 1) from the reversible effects of prior chemotherapy, with the exception of chemotherapy-induced alopecia and grade 2 peripheral neuropathy, unless in the opinion of the principal investigator the effects are not of clinical significance.\n* Any concurrent anticancer treatment.\n* Serious underlying medical or psychiatric illness or another condition that in the clinical judgment of the principal investigator is likely to interfere with the potential subject completing participation in the trial, based on safety concerns or otherwise.\n* Inability or unwillingness to adhere to the study protocol.\n* Unwillingness to receive ethanol.",{"count":19,"type":20},[23],"The clinical trial is a phase 1, single-arm trial that will evaluate the safety of the investigational treatment on metastatic pancreatic cancer and metastatic breast cancer. The investigational treatment will involve 2 cycles of a combination of intravenous melphalan, BCNU, vitamin B12b, and vitamin C with autologous hematopoietic stem cell infusion. A dose-escalation schedule is being employed for the vitamin C.",[211,27,28,212,213,214,215,216,217,218,219,220,221,222,30,223,224,225,226,227],"Pancreatic Adenocarcinoma Metastatic","Pancreatic Acinar Cell Carcinoma","Pancreatic Ductal Adenocarcinoma","Pancreatic Cancer","Metastatic Pancreatic Cancer","Metastatic Pancreatic Ductal Adenocarcinoma","Breast Cancer Metastatic","Breast Cancer Stage IV","Pancreatic Cancer Stage IV","HER2-negative Breast Cancer","HER2 Negative Breast Carcinoma","Adenocarcinoma of the Breast","Pancreas Cancer, Metastatic","Pancreas Cancer, Recurrent","Pancreas Cancer","Stage IV Pancreatic Cancer","Stage 4 Pancreatic Cancer",[229,230,231,232,154,233,234,235,236,237,238,239,240,241,242,243,244,245,246,247,248,249,250,251,252,253],"pancreatic adenocarcinoma","pancreatic cancer","BRCA","BRCA1","melphalan","BCNU","carmustine","vitamin C","vitamin B12b","autologous stem cell infusion","stage 4 pancreatic cancer","metastatic pancreatic cancer","pancreatic acinar cell carcinoma","pancreatic ductal adenocarcinoma","PDAC","breast cancer","stage 4 breast cancer","stage IV pancreatic cancer","stage IV breast cancer","stem cells","HER2-negative breast cancer","PALB2","metastatic breast cancer","BRCA pancreatic cancer","BRCA breast cancer","2026-01-27",{"date":256,"type":39},"2026-01-29",{"date":258,"type":39},"2021-01-13",{"date":99,"type":20},{"name":261,"class":197},"General Oncology, Inc.",{"id":263,"slug":264,"hasResults":11,"nctId":265,"briefTitle":266,"officialTitle":267,"acronym":268,"eligibilityCriteria":269,"healthyVolunteers":11,"sex":270,"minAge":17,"maxAge":4,"enrollmentInfo":271,"targetDuration":4,"studyType":21,"phases":273,"briefSummary":274,"conditions":275,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":278,"lastUpdatePostDateStruct":279,"startDateStruct":281,"completionDateStruct":283,"leadSponsor":284,"locationsCount":286},"100477538","phase-2-study-of-neoadjuvant-parp-inhibition-followed-by-radical-prostatectomy-in-patients-with-unfavorable-intermediate-risk-or-high-risk-prostate-cancer-with-select-hrr-gene-alterations-100477538","NCT05498272","Study of Neoadjuvant PARP Inhibition Followed by Radical Prostatectomy in Patients With Unfavorable Intermediate-Risk or High-Risk Prostate Cancer With Select HRR Gene Alterations","A Phase 2 Study of Neoadjuvant PARP Inhibition Followed by Radical Prostatectomy in Patients With Unfavorable Intermediate-Risk or High-Risk Prostate Cancer With Select HRR Gene Alterations (NePtune)","NePtune","Inclusion Criteria:\n\nSubject must meet all of the following applicable inclusion criteria to participate in this study:\n\n* Written informed consent and HIPAA authorization for release of personal health information prior to registration.\n* Age ≥ 18 years at the time of consent.\n* T stage 1-3 prostatic adenocarcinoma per AJCC staging manual Ed8.\n* Histologically confirmed adenocarcinoma of the prostate without histological variants comprising \\>50% of the sample. Patients with intraductal carcinoma are eligible.\n* Must have 3 core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained). Prostate biopsy must be within 7 months from registration. Less than 3 core biopsies are allowed if the patient has \\>1 cm or T3 disease on magnetic resonance imaging (MRI).\n* Localized unfavorable intermediate or high-risk prostate cancer patients. Patients must have at least one of the following features:\n\n  * Gleason ≥ 4+3 (grade group 3, 4, 5) OR\n  * PSA \\> 20 ng\u002FdL OR\n  * T3 disease NOTE: Patients with intraductal carcinoma are eligible independent of Gleason score, PSA and T stage.\n* Must have evidence of germline or somatic BRCA1\u002F2, PALB2, RAD51B, RAD51C, RAD51D, RAD54L2, BARD1, FANCA, BRIP1, CHEK2, ATM, and CDK12 gene alteration via standard of care CLIA based assay detection. Testing will be confirmed centrally but results of central testing not required for enrollment.\n* No evidence of metastatic disease as determined by radionuclide bone scan and CT\u002FMRI. Lymph nodes must be less than 20 mm in the short (transverse) axis.\n* Participants must be candidates for RP and considered surgically resectable by urologic evaluation.\n* ECOG Performance Status of 0-1 within 28 days prior to registration.\n* Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.\n\n  * White blood cell count ≥ 3,000\u002FmcL\n  * Absolute neutrophil count ≥ 1,500\u002FmcL\n  * Hemoglobin ≥ 10 g\u002FdL with no transfusion support in the past 28 days\n  * Platelets ≥ 100,000\u002FmcL\n  * Aspartate aminotransferase, alanine aminotransferase ≤ 2.5×ULN, and total bilirubin ≤ 1.5 x Institutional upper limit of normal\n  * Calculated creatinine clearance ≥ 51 mL\u002Fmin based on Cockcroft-Gault formula or 24 hour urine. NOTE: See the protocol for Cockcroft-Gault formula or 24 hour urine.\n* Life expectancy≥ 16 weeks.\n* Subjects must use a condom plus spermicide beginning prior to treatment Cycle 1 Day 1, during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential. See protocol for additional details.\n* As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.\n\nExclusion Criteria:\n\nSubjects meeting any of the criteria below may not participate in the study:\n\n* Active infection requiring systemic therapy.\n* Prior treatments not allowed: hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, apalutamide and others), CYP17 inhibitors (including abiraterone, TAK-700, galeterone, ketoconazole, and others), estrogens and radiation therapy. Prior bicalutamide is allowed if taken for \\\u003C 4 weeks prior to registration and there is a washout period of 2 weeks prior to the initiation of study treatment. LHRH agonist\u002Fantagonist therapy is allowed if begun within 4 weeks of registration. Prior 5-alpha reductase inhibitors are allowed but require a washout period of 2 weeks to initiation of study treatment.\n* Prior treatment with a PARP inhibitor.\n* Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy including:\n\n  * tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and TB testing in line with local practice).\n  * Known active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody at screening. Testing is not required unless there was a prior known positive hepatitis B or C test or hepatitis is suspected at screening. Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n* Known to have tested positive for human immunodeficiency virus (HIV) unless currently on effective anti-retroviral therapy with an undetectable viral load within 6 months.\n* Severe hepatic impairment (Child-Pugh Class C).\n* Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.\n* Pre-existing condition that warrants long-term corticosteroid use greater than the equivalent of 10 mg prednisone daily. Physiologic replacement is permitted. Topical, intra-articular steroids or inhaled corticosteroids are permitted.\n* Active cardiac disease, defined as:\n\n  * Myocardial infarction within 6 months of study treatment.\n  * Uncontrolled angina within 3 months of study treatment.\n  * Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless an echocardiogram performed within 3 months of the screening visit results in a left ventricular ejection fraction that is ≥ 45%.\n  * History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes)\n  * Other clinically significant cardiovascular disease within 6 months of registration.\n* Uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation \\>500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.\n* Individuals with a history of another malignancy are not eligible if the cancer is under active treatment or the cancer can be seen on radiology scans.\n* Major surgery within 4 weeks from start of treatment. Subjects must have recovered from any effects as the surgery as assessed by investigator discretion.\n* Treatment with any investigational drug within 28 days prior to registration.\n* Persistent toxicities Grade \\> 2 caused by previous cancer therapy (per Common Terminology Criteria for Adverse Event (CTCAE)).\n* Patients with myelodysplastic syndrome\u002Facute myeloid leukemia or with features suggestive of MDS\u002FAML.\n* Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorders that prohibits obtaining informed consent.\n* Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment.\n* Concomitant use of known strong CYP3A inhibitors. The required washout period prior to starting olaparib is 2 weeks.\n* Concomitant use of known strong or moderate CYP3A inducers. The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.\n* Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).\n* Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable, for timing refer to the protocol).\n* Patients with a known hypersensitivity to olaparib or any of the excipients of the product.","MALE",{"count":272,"type":20},32,[138],"Phase 2 open-label, single-arm clinical trial evaluating the efficacy and safety of neoadjuvant olaparib + LHRH agonist administered for 6 months prior to radical prostatectomy (RP) in men with unfavorable intermediate-risk or high-risk localized prostate cancer. All patients must have confirmed germline or somatic select HRR alterations. Germline and somatic mutation testing will be performed as part of commercially available CLIA assays and will be validated on a uniform platform centrally all patients retrospectively.\n\nEligible patients will receive treatment with olaparib + LHRH agonist. Following 6 months of therapy, patients will undergo RP with mandatory lymph node dissection. The lymph node dissection template will be at the discretion of the treating urologist. RP specimens will undergo pathology blinded independent central review. Following RP, patients will be followed for testosterone recovery and PSA progression.",[181,27,28,276,277],"Prostatic Adenocarcinoma","High-Risk Cancer","2026-01-22",{"date":280,"type":39},"2026-01-23",{"date":282,"type":39},"2023-02-01",{"date":194,"type":20},{"name":285,"class":46},"Rana McKay, MD",6,{"id":288,"slug":289,"hasResults":11,"nctId":290,"briefTitle":291,"officialTitle":292,"acronym":4,"eligibilityCriteria":293,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":294,"targetDuration":4,"studyType":21,"phases":296,"briefSummary":297,"conditions":298,"keywords":300,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":307,"lastUpdatePostDateStruct":308,"startDateStruct":310,"completionDateStruct":312,"leadSponsor":314,"locationsCount":198},"100545342","phase-1-study-of-ace-86225106-to-treat-patients-with-advanced-solid-tumors-100545342","NCT06380660","Study of ACE-86225106 to Treat Patients With Advanced Solid Tumors","A Phase I\u002FII, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of ACE-86225106 as Monotherapy in Patients With Advanced Solid Tumors","Inclusion Criteria:\n\n1. Provide written informed consent;\n2. Advanced solid tumors, difficult to treat or intolerant to standard treatment, suitable for investigational treatment;\n3. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;\n4. Has a life expectancy of at least 3 months;\n5. Has measurable disease per RECIST 1.1, castration-resistant prostate Ccancer (CRPC) patients can be assessed according to PCWG3;\n6. Adequate organ function and bone marrow function;\n7. Can provide tumor specimens and blood samples for Homologous Recombination Deficiency (HRD)\u002F Homologous Recombination Repair (HRR) related gene testing.\n\nExclusion Criteria:\n\n1. Receiving any anti-cancer drugs, major surgery, extensive radiation therapy, or local radiation therapy within protocol-defined wash-out period;\n2. Concomitant use of medications or herbal supplements known to be strong or moderate inhibitors or inducers of cytochrome P450 3A4 (CYP3A4);\n3. Receiving continuous corticosteroid treatment with a dose of prednisone greater than 10 mg\u002Fday or an equivalent dose.\n4. Receiving continuous treatment with prednisone at a dose of \\>10 mg\u002Fd or other corticosteroids at an equivalent dose for any reason.\n5. Any previous treatment-related toxicities have not recovered, i.e., to ≤ Grade 1 (as evaluated by NCI-CTCAE v5), except alopecia and other Grade 2 toxicities that are deemed not to affect the conduct of the study, as assessed by the sponsor and the clinical investigator.\n6. Spinal cord compression or brain metastases unless asymptomatic, treated and stable.\n7. Severe cardiovascular disorders.\n8. Myelodysplastic syndrome (MDS)\u002Facute myeloid leukemia (AML) or with evidence suggesting possible MDS\u002FAML.\n9. Concomitant diseases or conditions that would preclude the absorption of the investigational product.\n10. Active infections, or a known history of HIV infection, or a known active hepatitis B or C, or a known active tuberculosis.\n11. Other malignancies that require treatment within 3 years prior to first dose of study investigational product.\n12. Conditions with rapid deterioration during the screening period.\n13. Known allergy or hypersensitivity to the investigational product or any of the excipients of the investigational product.\n14. Has other medical conditions that at the discretion of investigator interfere with safety or efficacy evaluation, or affect treatment compliance.",{"count":295,"type":20},298,[23,138],"The purpose of this study is to determine if the experimental treatment with poly-ADP ribose polymerase (PARP) inhibitor, ACE-86225106 is safe, tolerable and has anti-cancer activity in adult patients with advanced solid tumors.",[299,27,28,180,141,181],"Solid Tumor, Adult",[301,302,303,304,244,305,306],"ACE-86225106","advanced solid tumors","PARP inhibitor","BRCA mutation","ovarian cancer","CRPC","2025-12-22",{"date":309,"type":39},"2025-12-29",{"date":311,"type":39},"2024-03-22",{"date":313,"type":20},"2029-03-21",{"name":315,"class":197},"Acerand Therapeutics (Shanghai) Limited",{"id":317,"slug":318,"hasResults":11,"nctId":319,"briefTitle":320,"officialTitle":320,"acronym":321,"eligibilityCriteria":322,"healthyVolunteers":323,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":324,"targetDuration":4,"studyType":326,"phases":4,"briefSummary":327,"conditions":328,"keywords":342,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":351,"lastUpdatePostDateStruct":352,"startDateStruct":354,"completionDateStruct":356,"leadSponsor":358,"locationsCount":47},"100339653","liquid-biopsy-evaluation-and-repository-development-at-princess-margaret-100339653","NCT03702309","Liquid Biopsy Evaluation and Repository Development at Princess Margaret","LIBERATE","Inclusion Criteria:\n\n1. Patients with either histological confirmation of a solid tumor or hematological malignancy, OR patients identified as high-risk for cancer (based on identified aberration in cancer predisposition gene or on hormonal and\u002For family history without known aberration).\n2. Patient must be ≥ 18 years old.\n3. All patients must have signed and dated an informed consent form for this LIBERATE study.\n4. If patients are being co-consented for a separate primary research study listed in Appendix I, they must fulfill the eligibility criteria for that separate primary research study. If there is a discrepancy in the eligibility criteria between protocols, the separate primary research study's criteria take precedence.\n\nExclusion Criteria:\n\nNone",true,{"count":325,"type":20},2500,"OBSERVATIONAL","The objective of this protocol is to develop an institution-wide liquid biopsy protocol that will establish a common process for collecting blood and corresponding archived tumor specimens for future research studies at the University Health Network's Princess Margaret Cancer Centre. Circulating cell-free nucleic acids (cfNA), including cell-free DNA (cfDNA) and cell-free RNA (cfRNA), are non-invasive, real-time biomarkers that can provide diagnostic and prognostic information before cancer diagnosis, during cancer treatment, and at disease progression. Cancer research scientists and clinicians at the Princess Margaret are interested in incorporating the collection of peripheral blood samples (\"liquid biopsies\") into research protocols as a means of non-invasively assessing tumor progression and response to treatment at multiple time points during a patient's course of disease.",[92,141,329,330,180,331,332,333,334,335,336,27,28,337,338,339,340,341],"Lung Cancer","Colon Cancer","Melanoma","Lymphoma","Leukemia","Mutation","Lynch Syndrome","Cowden Syndrome","Uterine Cancer","Myeloma","Kidney Cancer","Head and Neck Cancer","Meningioma",[343,344,345,346,347,348,349,350],"High Risk","Liquid Biopsy","Circulating Tumor DNA","Blood","Molecular Profiling","Next Generation Sequencing","Solid Tumors","Hematological","2025-11-25",{"date":353,"type":39},"2025-11-26",{"date":355,"type":39},"2017-08-03",{"date":357,"type":20},"2026-07-06",{"name":359,"class":46},"University Health Network, Toronto",{"id":361,"slug":362,"hasResults":11,"nctId":363,"briefTitle":364,"officialTitle":365,"acronym":366,"eligibilityCriteria":367,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":368,"targetDuration":4,"studyType":21,"phases":370,"briefSummary":371,"conditions":372,"keywords":375,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":381,"lastUpdatePostDateStruct":382,"startDateStruct":384,"completionDateStruct":386,"leadSponsor":388,"locationsCount":390},"100531548","phase-2-evaluating-the-addition-of-elacestrant-oral-serd-to-olaparib-parp-inhibitor-in-patients-with-advancedmetastatic-hrher2--breast-cancer-100531548","NCT06201234","Evaluating the Addition of Elacestrant (Oral SERD) to Olaparib (PARP-inhibitor) in Patients With Advanced\u002FMetastatic HR+\u002FHER2- Breast Cancer","Phase II Study Evaluating the Addition of Elacestrant, an Oral Selective Estrogen Receptor Degrader (SERD), to Standard-of-care Olaparib in Patients With Hormone Receptor (HR)-Positive, HER2-negative Locally Advanced or Metastatic Breast Cancer With gBRCA1\u002F2 Mutations","ELEMENT","Inclusion Criteria:\n\nPatients will be eligible for study participation only if they comply with the following criteria:\n\n1. Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for scheduled visit, the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.\n2. Female or male patients.\n3. Age at study entry of at least 18 years.\n4. Locally advanced or metastatic breast cancer that is HR-positive (ER and\u002For PgR ≥ 10% of stained cells at IHC) and HER2-negative (IHC 0 or 1+, or 2+ and ISH negative according to ASCO\u002FCAP guidelines).\n5. Patients with deleterious or suspected deleterious gBRCA1\u002F2 mutation detected upon local testing.\n6. Willingness and ability to provide archived formalin fixed paraffin embedded tissue (FFPE) block or a partial block from archived tumor or metastasis.\n7. Indication for standard-of-care PARP inhibitor therapy and planned treatment with olaparib.\n8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.\n9. Resolution of all acute toxic effects of prior anti-cancer therapy including endocrine therapy or surgical procedures to NCI CTCAE version 5.0 grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).\n10. Life-expectancy \\> 6 months.\n11. For female patients: patients of childbearing potential (defined as not post-menopausal and not permanently sterile \\[latter defined as having undergone hysterectomy, bilateral salpingectomy, or bilateral oophorectomy\\]) require a negative serum or urinary pregnancy test within 72 hours before starting treatment in this study (in this case, patients need to use highly effective non-hormonal contraceptive methods as specified in the protocol).\n\nFor male patients: during the intervention period and for at least 120 days after the last dose of elacestrant, patients should refrain from heterosexual intercourse or use a condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak), and they should refrain from donating sperm.\n\nExclusion Criteria:\n\nPatients will be ineligible for study participation if they fulfill any of the following criteria:\n\n1. Known hypersensitivity reaction to one of the compounds, excipients, or substances used in this protocol.\n2. Active or newly diagnosed CNS metastases, including leptomeningeal carcinomatosis, carcinomatous meningitis, or radiographic signs of CNS hemorrhage. Note: Patients with stable brain metastases are allowed. Radiotherapeutic treatment must be completed 1 week before planned day 1 of study therapy.\n3. Presence of symptomatic metastatic visceral disease that are at risk of life-threatening complications in the short term, including but not confined to massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or fulminant liver involvement.\n4. Inadequate organ function prior to enrolment including:\n\n   * Hemoglobin \\\u003C 9 g\u002FdL (\\\u003C 5.6 mmol\u002FL)\n   * Absolute neutrophil count (ANC) \\\u003C 1500\u002Fmm³ (\\\u003C 1.5 x 109\u002FL)\n   * Platelets \\\u003C 100,000\u002Fmm³ (\\\u003C 100 x 109\u002FL)\n   * Alanine aminotransferase (ALT\u002FSGPT) and\u002For aspartate aminotransferase (AST\u002FSGOT) \\> 3 x upper normal limits (ULN). If the patient has liver metastases, ALT and AST should not be ≥ 5 x ULN.\n   * Alkaline phosphatase (ALP) \\> 2.5 x ULN\n   * Total serum bilirubin \\> 1.5 x ULN (exception: patients with Gilbert's syndrome permitted up to ≤ 3 x ULN)\n   * Serum creatinine \\> 1.5 x ULN or estimated creatinine clearance \\\u003C 50 mL\u002Fmin as calculated using the standard method for the institution.\n5. Existing contraindication against the use of the elacestrant or olaparib.\n6. Prior treatment with PARP inhibitors.\n7. Female patients: pregnancy or lactation at the time of randomization or intention to become pregnant during the study and for a predefined period after the end of treatment (as described in protocol).\n\n   Male patients: intention to get a child during the study and for a predefined period after the end of treatment (as described in protocol).\n\n   According to the treatment received during the study, required contraception timelines for female and male patients are described in the study protocol.\n8. Any of the following within 6 months prior to enrolment: myocardial infarction, severe\u002Funstable angina, ongoing grade ≥ 2 cardiac dysrhythmias, prolonged QT corrected by Fridericia's formula (QTcF) grade ≥ 2, uncontrolled atrial fibrillation of any grade, coronary\u002Fperipheral artery bypass graft, heart failure of New York Heart Association (NYHA) Class II or greater, or cerebrovascular accident including transient ischemic attack.\n9. Uncontrolled hypertension at the time of screening (systolic BP \\> 140 mmHg or diastolic BP \\> 90 mmHg that has not been adequately treated or controlled).\n10. Active and current anticoagulation for treatment purposes of thrombotic events occurring \\\u003C 6 months before enrolment is not allowed (prophylactic anticoagulation, however, is acceptable). Treatment with an anticoagulant for a thrombotic event occurring \\> 6 months before enrolment, or for an otherwise stable and allowed medical condition (e.g., well controlled atrial fibrillation) is acceptable, provided dose and coagulation parameters (as defined by local standard of care) are stable for at least 28 days prior to the first dose of study drug.\n11. Known difficulty in tolerating oral medications or conditions which would impair absorption of oral medications such as: uncontrolled nausea or vomiting (i.e., CTCAE ≥ grade 3 despite antiemetic therapy), ongoing gastrointestinal obstruction\u002Fmotility disorder, malabsorption syndrome, or prior gastric bypass.\n12. History of endometrial intraepithelial neoplasia in patients who have not undergone a hysterectomy.\n13. Malignant disease other than breast cancer, active or being disease-free for less than 5 years (except carcinoma in situ of the cervix, DCIS, and non-melanomatous skin cancer adequately treated).\n14. Uncontrolled significant active infections including HBV, HCV, and\u002For HIV. Patients with a positive hepatitis B surface antigen result or a positive hepatitis C antibody test result at screening or within 3 months before first dose of study treatment are excluded, except for the following:\n\n    * Participants with positive anti-HBs antibody titer and confirmatory negative hepatitis B DNA polymerase chain reaction.\n    * Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if they have both completed curative therapy and have a hepatitis C viral load \\\u003C quantifiable limit.\n15. Any severe, acute, uncontrolled, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational or non-investigational products administration, or 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. Moreover, patients who, by virtue of an order issued by judicial or administrative authorities, are committed to an institution or those who cannot take part in clinical trials are excluded from this study.\n16. History of significant neurological or psychiatric disorders including psychotic disorders, dementia, or seizures that would prohibit the understanding and giving of informed consent.\n17. Unable or unwilling to avoid medications, supplements (e.g., St. John's wort), or foods (e.g., grapefruit, pomegranate, 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, or foods are discontinued for at least 14 days prior to study entry and for the duration of the study.\n18. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.\n19. Receipt of live attenuated vaccination within 30 days prior to study entry. COVID-19 vaccines that do not contain live viruses are allowed (at least one week prior to study entry).",{"count":369,"type":20},176,[138],"Trial design:\n\nPhase II, prospective, multi-center, randomized, open label, parallel group study in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1\u002F2 mutation, with 2:1 randomization into Arm A (olaparib + elacestrant) or arm B (olaparib). Treatment in either arm will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study.\n\nTrial population:\n\nPatients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1\u002F2 mutation, with an indication for standard-of-care PARP inhibitor therapy and planned treatment with olaparib, an ECOG performance status of 0-2 and life expectancy of \\> 6 months, with normal bone marrow and kidney functions and no active or newly diagnosed central nervous system (CNS) metastases or symptomatic metastatic visceral disease at risk of life-threatening complications.\n\nInterventions:\n\nPatients randomized to Arm A will receive 600 mg olaparib daily and 400 mg elacestrant daily, while patients randomized to Arm B will receive 600 mg olaparib daily. Blood tests (hematology, biochemistry) will be performed at the beginning of every cycle, and imaging for tumor assessment (chest and abdominopelvic imaging) as well as QoL assessments will be performed every three months and in case of suspicion of progression\u002Fend of study.",[373,374,27,28],"Hormone Receptor Positive HER-2 Negative Breast Cancer","Advanced or Metastatic Breast Cancer",[376,377,378,379,380],"Elacestrant","Olaparib","Breast cancer","Metastases","Palliative therapy","2025-11-24",{"date":383,"type":39},"2025-12-01",{"date":385,"type":39},"2024-12-13",{"date":387,"type":20},"2028-12-31",{"name":389,"class":46},"GBG Forschungs GmbH",36,{"id":392,"slug":393,"hasResults":11,"nctId":394,"briefTitle":395,"officialTitle":396,"acronym":397,"eligibilityCriteria":398,"healthyVolunteers":11,"sex":79,"minAge":17,"maxAge":4,"enrollmentInfo":399,"targetDuration":4,"studyType":326,"phases":4,"briefSummary":401,"conditions":402,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":403,"lastUpdatePostDateStruct":404,"startDateStruct":406,"completionDateStruct":408,"leadSponsor":410,"locationsCount":412},"100612397","brca-mutation-carriers-platform-a-multicenter-study-100612397","NCT07253051","BRCA Mutation Carriers' Platform a Multicenter Study","BRCA Mutation Carriers' Platform, a Multicenter Study","BRCA_ENDORSE","Inclusion Criteria:\n\n* All women who are 18 years of age or older;\n* All women who known to be carriers of a pathogenetic mutation class 4 and 5 of the International Agency of Research on Cancer classification) of the BRCA1 or BRCA2 genes.\n\nExclusion Criteria:\n\n* Age \\\u003C 18 years old;\n* No pathogenetic mutation carriers.",{"count":400,"type":20},10000,"Subjects who carry mutations in breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2 genes) are at higher risk of developing cancers. Despite the cumulative amount of evidence published in the literature in the last two decades, the management of BRCA mutation carriers is still not completely defined.\n\nSince the prevalence of the mutation is estimated to be 1:400 - 1:500 individuals, the total number of BRCA mutation carriers should be around 140.000 - 150.000 in the Italian population. It is estimated that 87% of women with BRCA mutations will experience, in their lifetime, a tumor with a genetic origin. About 20% of the 5200 ovarian cancer cases diagnosed each year in Italy has a genetic origin and could potentially be the object of primary prevention. To date, and to the best of our knowledge, a national prospective data collection on women with BRCA mutations has not been yet established.",[27,28],"2025-11-19",{"date":405,"type":39},"2025-11-28",{"date":407,"type":39},"2025-04-05",{"date":409,"type":20},"2045-12-31",{"name":411,"class":46},"Fondazione Policlinico Universitario Agostino Gemelli IRCCS",40,{"id":414,"slug":415,"hasResults":11,"nctId":416,"briefTitle":417,"officialTitle":418,"acronym":4,"eligibilityCriteria":419,"healthyVolunteers":323,"sex":16,"minAge":420,"maxAge":4,"enrollmentInfo":421,"targetDuration":4,"studyType":21,"phases":423,"briefSummary":424,"conditions":425,"keywords":443,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":448,"lastUpdatePostDateStruct":449,"startDateStruct":451,"completionDateStruct":453,"leadSponsor":455,"locationsCount":456},"100471529","an-intervention-to-increase-genetic-testing-in-families-who-may-share-a-gene-mutation-related-to-cancer-risk-and-an-intervention-to-help-patients-and-their-primary-care-providers-stay-up-to-date-about-uncertain-genetic-test-results-100471529","NCT05420064","An Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About Uncertain Genetic Test Results","Digital Technology to Enhance Access to and Effectiveness of Cancer Genetic Counseling: Effective Familial OutReach Via Tele-genetics (EfFORT) Trial & Supporting Test Result Interpretation and Variant Education (STRIVE) Trial","Inclusion Criteria:\n\nEfFORT Trial Probands\n\n* Current MSK patient\n* Received post-test genetic counseling from MSK Clinical Genetics Service within the last 3 months (or within the last year for the de-identified non-randomized control probands)\n* 25 years of age or older\n* Self-reported \"very well\" comprehension of written and verbal English language or Spanish language\n* Has at least one ARR who meets criteria for study enrollment (see below)\n* First in the family to test positive for PV at MSK in any of the following cancer susceptibility genes, or an ARR of an MSK proband who converted to the proband role:\n\nAPC I1307K, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDKN2A (P16), CHEK2, EPCAM, GREM1, MLH1, MSH2, MSH6, PALB2, PMS2, POLD1, POLE, PTEN, RAD51C, RAD51D, SMAD4, BAP1, DICER1, FH, FLCN, HOXB13, KIT, MAX, MEN1, MET, MITF, PTCH1, RAD51B, RET, SDHB, SDHC, SDHD, STK11, SUFU, TMEM127, TSC1, TSC2, VHL\n\nPrincipal Investigator discretion will be used to determine whether specific variants within the above genes meet a clinical actionability threshold to warrant familial genetic testing.\n\nEfFORT Trial At-Risk Relatives (ARRs):\n\n* Biological first-, second-, or third- degree relative of enrolled MSK proband\n* 25 years of age or older\n* Resides within the United States\n* Self-reported medical insurance which can be in or out of network with MSK\n* Self-reported \"very well\" comprehension of written and verbal English language\n\nSTRIVE Trial VUS Patients\n\n* Current MSK patient\n* Received post-test genetic counseling from MSK Clinical Genetics Service within the last 3 months\n* 25 years of age or older\n* Self-reported \"very well\" comprehension of written and verbal English language or Spanish language\n* Has a VUS identified in any of the following cancer predisposition genes:\n\nAPC, ATM, AXIN2, BAP1, BARD1, BLM, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A (P16), CHEK2, CTNNA1, DICER1, ELOC, EPCAM, FH, FLCN, GREM1, HOXB13, KEAP1, MAX, MBD4, MEN1, MET, MITF, MLH1, MLH3, MSH2, MSH3, MSH6, MUTYH, NF1, NF2, NTHL1, PALB2, PMS2, POLD1, POLE, POT1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RET, RNF43, RPS20, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMAD4, STK11, TERT, TMEM127, TP53, TSC1, TSC2, VHL\n\nSTRIVE Trial PCP Providers:\n\n* Designated healthcare provider for an enrolled VUS patient\n* Resides within the United States\n\nExclusion Criteria:\n\nEfFORT Trial Probands\n\n* Is unwilling or unable to provide informed consent\n* Is unwilling or unable to create a MyMSK patient portal account (see section 3.0 on MyMSK patient usage at MSK and CGS)\n* Does not have an email address\n* Has enrolled in the STRIVE trial\n\nEfFORT Trial At-Risk Relatives (ARRs):\n\n* Is unwilling or unable to provide informed consent\n* Is unwilling or unable to create a MyMSK patient portal account\n* Has previously undergone genetic testing for the familial PV\n* Does not have an email address\n* Has opted out of study contact\n\nSTRIVE Trial VUS Patients\n\n* Is unwilling or unable to provide informed consent\n* Is unwilling or unable to create a MyMSK patient portal account (see section 3.0 on MyMSK patient usage at MSK and CGS)\n* Does not have an email address\n* Has enrolled in the EfFORT trial\n\nSTRIVE Trial PCP Providers\n\n* Contact information not available","25 Years",{"count":422,"type":20},1000,[83],"The purpose of this study is to examine the impact of new cancer genetic counseling models that aim to increase patient engagement with the genetics team. To do this, the study consists of two trials to evaluate two related interventions. The first trial is the EfFORT Trial, which evaluates a cascade genetic testing intervention. Cascade testing is the process of offering genetic testing to people who are at risk of having inherited a possibly harmful gene change that has been found in their family. The study will look at how often genetic testing occurs when healthcare providers have permission to reach out to family members to recommend genetic testing and to help those who are interested get tested. The study will look at whether this cascade testing intervention is practical and effective. The study would like to see how this approach of healthcare providers reaching out directly to family members compares with the usual approach of patients telling their family members about the recommendation to get genetic testing. The second trial is the STRIVE Trial, which evaluates an intervention designed to help patients who receive an uncertain result from genetic testing (also called a \"variant of uncertain significance\") stay connected with their genetics care team, and to help patients and their primary care providers stay up-to-date about the meaning of uncertain genetic test results. The study will look at whether an intervention that consists of a study online portal for patients with uncertain genetic test results and their primary care providers will help them to stay up-to-date on the meaning of uncertain genetic test results. The study would like to see how this intervention compares to the usual approach of encouraging patients to re-contact their genetics care team on their own about a year after getting genetic testing.\"",[27,426,427,28,428,429,29,430,431,432,433,434,145,435,30,436,437,438,439,440,441,442],"POLD1 Gene Mutation","CDKN2A Mutation","POLE Gene Mutation","APC Gene Mutation","MLH1 Gene Mutation","BARD1 Gene Mutation","MSH2 Gene Mutation","BRIP1 Gene Mutation","MSH6 Gene Mutation","PMS2 Gene Mutation","EPCAM Gene Mutation","RAD51C Gene Mutation","BMPR1A Gene Mutation","RAD51D Gene Mutation","SMAD4","PTEN Gene Mutation","GREM1",[444,445,446,447],"EfFORT","Memorial Sloan Kettering Cancer Center","Genetic Testing","22-023","2025-11-10",{"date":450,"type":39},"2025-11-12",{"date":452,"type":39},"2022-12-01",{"date":454,"type":20},"2026-11-30",{"name":445,"class":46},8,{"id":458,"slug":459,"hasResults":11,"nctId":460,"briefTitle":461,"officialTitle":461,"acronym":4,"eligibilityCriteria":462,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":463,"targetDuration":4,"studyType":21,"phases":465,"briefSummary":466,"conditions":467,"keywords":469,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":471,"lastUpdatePostDateStruct":472,"startDateStruct":474,"completionDateStruct":476,"leadSponsor":478,"locationsCount":479},"100553614","phase-1-phase-ib-study-of-axatilimab-in-combination-with-olaparib-in-brca12-and-palb2--associated-metastatic-her2-negative-breast-cancer-100553614","NCT06488378","Phase Ib Study of Axatilimab in Combination With Olaparib in BRCA1\u002F2 and PALB2- Associated Metastatic HER2-negative Breast Cancer","Inclusion Criteria:\n\n* Participants must have histologically or cytologically confirmed metastatic or unresectable HER2 negative breast cancer, including HER2 low (IHC 2+\u002FISH-, IHC 1+). Any ER and PR expressions are permitted but must be known. Patients with hormone receptor (HR) positive disease, defined by either ER and\u002For PR positivity, must have progressed or are intolerant to all available endocrine therapy regimens, or not candidates to further endocrine therapy-based approaches.\n* Documented germline or somatic mutation in BRCA1, BRCA2, or germline mutation in PALB2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental\u002Flead to loss of function). Testing may be completed by any CLIA-certified laboratory.\n* Participants must have evaluable or measurable disease per RECIST 1.1 criteria. NOTE: If the only site of measurable of disease has been previously irradiated, there must be evidence of post-radiation progression.\n* Patients must have received no more than 2 prior lines of cytotoxic chemotherapy for metastatic disease. Antibody drug conjugates will count towards prior lines of cytotoxic chemotherapy, as well as checkpoint inhibitors. For the purposes of this study, prior treatment with hormonal therapy and non-hormonal targeted therapy, as well as the combination of an aromatase inhibitor and everolimus, are not counted as a prior cytotoxic therapy.\n* Age ≥18 years.\n* ECOG performance ≤ 2.\n* Participants must meet the following organ and marrow function as defined below:\n\n  * leukocytes ≥ 3000\u002FmcL\n  * absolute neutrophil count ≥ 1.5 x 109\u002FL\n  * platelets ≥ 100 x 109\u002FL\n  * total bilirubin ≤ 1.5x institutional upper limit of normal (ULN)\n  * AST(SGOT)\u002FALT(SGPT) ≤ 2.5x × institutional ULN or ≤5 × institutional ULN for participants with documented liver metastases\n  * Creatinine clearance ≥ 51 mL\u002Fmin (using Cockcroft-Gault equation)\n* Participants who are HBsAg positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks and have undetectable HBV viral load prior to registration.\n\n  * Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.\n  * Hepatitis B screening tests are not required unless:\n\n    * Known history of HBV infection\n    * As mandated by local health authority\n* Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening.\n\n  * Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to registration.\n  * Hepatitis C screening tests are not required unless:\n\n    * Known history of HCV infection\n    * As mandated by local health authority\n* HIV-infected participants must have well-controlled HIV on ART, defined as:\n\n  * a. Participants on ART must have a CD4+ T-cell count ≥350 cells\u002Fmm3 at the time of screening.\n  * b. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening.\n  * c. It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months.\n  * d. Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the study.\n  * e. The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors\u002Finducers\u002Fsubstrates (https:\u002F\u002Fwww.fda.gov\u002Fdrugs\u002Fdrug-interactions-labeling\u002Fdrug-development-and- drug-interactions-table-substrates-inhibitors-and-inducers)\n* Ability to swallow and retain oral study medication\n* Patients with a history of treated central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria:\n\n  * Disease outside the CNS is present\n  * No clinical evidence of progression in the CNS since completion of CNS-directed therapy\n  * Minimum of 2 weeks between completion of radiotherapy and Cycle 1 Day 1\n  * Recovery from significant (≥ Grade 3) acute toxicity with no requirement for escalating doses of corticosteroid over the 7 days prior to treatment start.\n* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.\n* Female participants must be postmenopausal or must have a negative serum pregnancy test performed during screening. Postmenopausal is defined as:\n\n  * Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments\n  * Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50.\n  * Radiation-induced oophorectomy with last menses \\>1 year ago\n  * Chemotherapy-induced menopause with \\>1 year interval since last menses\n  * Bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago\n* The effects of axatilimab and olaparib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men who are sexually active with WOCBP must agree to use adequate contraception for the duration of study participation and for 4 months after discontinuation of treatment.\n* Participants must be willing to undergo 3 research biopsies: at baseline, after 2 weeks of olaparib monotherapy, and after 2 cycles of combination therapy. If biopsy is not feasible or safe, OR if the only area accessible to biopsy is also the only site of measurable disease per RECIST 1.1 criteria, permission must be obtained from the DFCI sponsor- investigator to forgo the mandatory research biopsies. Formal eligibility exception would not be required in these circumstances.\n* Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n* Clinical progression on a PARP inhibitor, or within 12 months of receipt of a PARP inhibitor, including but not limited to olaparib.\n* Any previous treatment with CSF1R antibody.\n* Patients who have had prior systemic chemotherapy, immune therapy, or investigational therapy within three weeks of initiation of protocol therapy. Endocrine therapy must have been discontinued at least 7 days prior to initiation of protocol therapy. Patients may receive bisphosphonates or denosumab during the study.\n* Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> Grade 1) with the exception of alopecia, are excluded.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to axatilimab or olaparib.\n* Participants receiving any medications or substances that are strong or moderate inhibitors or inducers of CYP450 enzyme(s) are ineligible. This also includes strong or moderate CYP3A inhibitors and inducers. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference.\n* Participants with a QTcF of \\>470msec on screening ECG\n* Patients with a history of myelodysplastic syndrome (MDS)\u002Facute myeloid leukemia (AML) or with features suggestive of MDS\u002FAML\n* Participants unable to swallow orally administered medication and participants with gastrointestinal disorders that are likely to interfere with absorption of the study medications in the opinion of the treating investigator (e.g. malabsorption syndrome or major stomach or bowel resections).\n* Uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* History of pneumonitis or ILD, or evidence of pneumonitis\u002FILD on baseline imaging\n* Known active or latent tuberculosis\n* Patients with major surgical procedure within 28 days prior to initiation of protocol therapy.",{"count":464,"type":20},20,[23],"This research is being done to evaluate the safety and tolerability of the new drug, axatilimab, in combination with olaparib (a standard of care treatment) in Breast Cancer 1\u002F2 genes (BRCA 1\u002F2) and PALB2 associated HER2-negative metastatic breast cancer.\n\nThe names of the study drugs involved in this study are:\n\n* Axatilimab (a type of antibody)\n* Olaparib (a type of PARP inhibitor)",[141,468,220,27,28],"PALB2-Mutated Breast Carcinoma",[141,468,220,27,28,470],"Metastatic HER2-negative Breast Cancer","2025-08-18",{"date":473,"type":39},"2025-08-22",{"date":475,"type":39},"2024-08-13",{"date":477,"type":20},"2029-03-01",{"name":166,"class":46},3,{"id":481,"slug":482,"hasResults":11,"nctId":483,"briefTitle":484,"officialTitle":485,"acronym":4,"eligibilityCriteria":486,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":487,"targetDuration":4,"studyType":21,"phases":489,"briefSummary":490,"conditions":491,"keywords":496,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":499,"lastUpdatePostDateStruct":500,"startDateStruct":502,"completionDateStruct":504,"leadSponsor":506,"locationsCount":479},"100476579","phase-2-novel-neoadjuvant-and-adjuvant-strategy-for-germline-brca-12-mutated-triple-negative-breast-cancer-100476579","NCT05485766","Novel Neoadjuvant and Adjuvant Strategy for Germline BRCA 1\u002F2 Mutated Triple Negative Breast Cancer","Neoadjuvant and Adjuvant Olaparib Plus Pembrolizumab Following Platinum Based Chemotherapy Plus Pembrolizumab for Germline BRCA Mutated Triple Negative Breast Cancer (WJOG14020B\u002FOPERETTA)","Inclusion Criteria:\n\n* Male\u002Ffemale subjects who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of invasive breast cancer\n* Have histologically confirmed TNBC, as defined by the most recent ASCO\u002FCAP guidelines.\n* Confirmed germline BRCA 1\u002F2 mutated.\n* Have previously untreated locally advanced non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per AJCC for breast cancer staging criteria version 7 as assessed by the investigator based on radiological and\u002For clinical assessment:\n\n  1. T1c, N1-N2\n  2. T2, N0-N2\n  3. T3, N0-N2\n  4. T4a-d, N0-N2\n* It has been confirmed that there is no distant metastasis to each organ by the following tests. Chest: Contrast CT or FDG-PET\u002FCT Abdominal: Contract CT\\* or FDG-PET\u002FCT Bone: Bone scintigraphy or FDG-PET\u002FCT Brain: In the case of no central nervous system symptoms, examination for brain metastasis is not required.\n* The subject (or legally acceptable representative if applicable) provides written informed consent for the trial.\n* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n* Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to the start of study treatment.\n\nExclusion Criteria:\n\n* Subjects who has a positive urine pregnancy test within 72 hours prior to registration\n* Has diagnosed as inflammatory breast cancer.\n* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor .\n* Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug.\n* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.\n* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.\n* Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.\n* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and investigational drugs used in this study and\u002For any of their excipients.\n* Has active autoimmune disease that has required systemic treatment in the past 2 years\n* Has a history of (non-infectious) pneumonitis\u002Finterstitial lung disease .\n* Has an active infection requiring systemic therapy.\n* Has a known history of Human Immunodeficiency Virus (HIV) infection.\n* Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \\[HbsAg\\] reactive) or known active Hepatitis C virus (defined as HCV RNA \\[qualitative\\] is detected) infection.\n* Has a known history of active TB (Bacillus Tuberculosis).\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality.\n* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n* Is pregnant or breastfeeding, or expecting to conceive or father children.\n* Has had an allogenic tissue\u002Fsolid organ transplant.\n* Has received pre-treatment with Olaparib or other PARP inhibitors.\n* Has significant cardiovascular disease\n* Has a resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions.\n* Subject has myelodysplastic syndrome (MDS)\u002Facute myeloid leukemia (AML) or with features suggestive of MDS\u002FAML.\n* Subject received colony-stimulating factors within 28 days prior to the first dose of study intervention.\n* Subject is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.\n* Is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption.\n* Is, in the judgement of the investigator, unlikely to comply with the study procedures, restrictions, and requirements of the study.\n* Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study.\n* Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study.",{"count":488,"type":20},23,[138],"This is a Phase II, single-arm, open label study to evaluate Olaparib plus Pembrolizumab following platinum-based chemotherapy plus Pembrolizumab as neoadjuvant therapy for germline BRCA (gBRCA) 1\u002F2 mutated triple negative breast cancer (TNBC).\n\nPembrolizumab in combination with weekly paclitaxel and carboplatin (treatment 1) is followed by Pembrolizumab in combination with Olaparib (treatment 2) in neoadjuvant setting and Pembrolizumab in combination with Olaparib in adjuvant setting will be studied",[492,493,494,141,27,28,59,495],"Triple Negative Breast Neoplasms","Triple Negative Breast Cancer","Breast Neoplasms","BRCA-Associated Breast Carcinoma",[497,498],"BRCA1 protein","BRCA2 protein","2025-03-17",{"date":501,"type":39},"2025-03-20",{"date":503,"type":39},"2024-07-16",{"date":505,"type":20},"2028-09-30",{"name":507,"class":46},"Okayama University",{"id":509,"slug":510,"hasResults":11,"nctId":511,"briefTitle":512,"officialTitle":513,"acronym":514,"eligibilityCriteria":515,"healthyVolunteers":11,"sex":270,"minAge":516,"maxAge":517,"enrollmentInfo":518,"targetDuration":520,"studyType":326,"phases":4,"briefSummary":521,"conditions":522,"keywords":526,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":530,"lastUpdatePostDateStruct":531,"startDateStruct":533,"completionDateStruct":535,"leadSponsor":537,"locationsCount":47},"100449217","prostate-cancer-genetic-risk-evaluation-and-screening-study-100449217","NCT05129605","Prostate Cancer Genetic Risk Evaluation and Screening Study","Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS)","PROGRESS","Inclusion Criteria:\n\n* Men 35-74 years old\n* No known diagnosis of prostate cancer\n* Life expectancy \\>10 years\n* Meet cohort A, B, or C criteria\n* Cohort A: Documented pathogenic or likely pathogenic germline genetic mutation in a prostate cancer risk gene from a CLIA-certified laboratory (ATM, ATR, BRCA1, BRCA2, BRIP1, CHEK2, EPCAM, FANCA, GEN1, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51C, RAD51D, TP53)\n* Cohort B: A strong family history suggestive of high genetic risk for prostate cancer with negative clinical genetic testing\n* Cohort C: Individuals who self-identify as Black American or Black Caribbean with both parents and all four grandparents of Black\u002FAfrican ancestry\n\nExclusion Criteria:\n\n* Prior diagnosis or treatment of prostate cancer\n* Inability to undergo prostate MRI\n* Inability to receive MRI contrast agent","35 Years","74 Years",{"count":519,"type":20},400,"10 Years","This study aims to define the natural history of men at high genetic risk for prostate cancer on the basis of specific germline genetic mutations, family history, or Black\u002FAfrican ancestry and evaluate the utility of prostate MRI as a screening tool. The hypothesis is that this targeted population of men are at elevated risk of developing prostate cancer compared to the general population, and enhanced screening with MRI will enable early detection and diagnosis of potentially aggressive prostate cancer, characterization of the penetrance of specific mutations, and potentially identify new genetic risk mutations.",[523,181,28,27,29,524,335,525],"Prostatic Neoplasm","MMR Mutation","Genetic Predisposition to Disease",[154,232,527,335,528,529],"Mismatch Repair Deficiency","HOXB13","Family History of Prostate Cancer","2024-10-05",{"date":532,"type":39},"2024-10-09",{"date":534,"type":39},"2020-02-12",{"date":536,"type":20},"2040-12",{"name":538,"class":46},"Massachusetts General Hospital",{"id":540,"slug":541,"hasResults":11,"nctId":542,"briefTitle":543,"officialTitle":543,"acronym":544,"eligibilityCriteria":545,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":546,"targetDuration":4,"studyType":21,"phases":548,"briefSummary":549,"conditions":550,"keywords":552,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":554,"lastUpdatePostDateStruct":555,"startDateStruct":557,"completionDateStruct":559,"leadSponsor":561,"locationsCount":47},"100508253","contribution-of-oncogenetics-in-breast-cancer-in-reunion-epidemiology-of-breast-cancer-in-reunion-study-of-the-reunion-mutation-on-brca2-100508253","NCT05898009","Contribution of Oncogenetics in Breast Cancer in Reunion Epidemiology of Breast Cancer in Reunion: Study of the Reunion Mutation on BRCA2","CanSeR-OGen","Inclusion Criteria:\n\n* Domiciled in Reunion at the time of the diagnosis\n* Who is diagnosed with a first breast cancer (in situ or invasive) confirmed by anatomopathological examination during the inclusion period Or Who is diagnosed with a second breast cancer (in situ or invasive) confirmed by pathological examination during the inclusion period, contralateral to the first or at least 5 years after remission of the first\n* Having agreed to participate in the study;\n* Affiliates or beneficiaries of a social security scheme\n\nExclusion Criteria:\n\n* Carriers of breast lymphoma,\n* Minor patients or patients under guardianship or curatorship",{"count":547,"type":20},300,[83],"In mainland France, breast cancer is the most common cancer in women, with an estimated incidence of over 58,000 new cases. Even if breast cancer is a cancer with a good prognosis, it is responsible for more than 12,000 deaths per year (first cause of death by cancer in women in France).\n\nBreast cancer is a multifactorial disease, which results from the interaction between environmental, lifestyle, hormonal and genetic risk factors.\n\nIn Reunion, more than 400 cases of breast cancer are diagnosed annually. As in mainland France, it is by far the most common cancer in Reunionese women, and its incidence continues to increase significantly since the age-standardized incidence rate increased by 28% between 2007 and 2017 to establish at 64.2\u002F100,000 AP.\n\nTwo studies carried out in patients carrying mutations in the breast-ovary predisposition genes in Reunion, showed that more than 50% of patients carrying BRCA mutation have a mutation specific to the Reunion population on the BRCA2 gene.\n\nThese two studies, which confirm the genetic specificities of Reunion already described in other pathologies (Mucoviscidosis or Friedreich's Ataxia), suggest that this mutation could have a significant frequency in patients with breast cancer. Thus, evaluating the prevalence of this mutation in patients with breast cancer in Réunion would make it possible to adapt the indications for access to the oncogenetics consultation and the associated preventive measures",[141,551,28],"Genetic Disease",[553],"reunion","2024-08-20",{"date":556,"type":39},"2024-08-22",{"date":558,"type":39},"2023-10-19",{"date":560,"type":20},"2026-03-22",{"name":562,"class":46},"Centre Hospitalier Universitaire de la Réunion",{"id":564,"slug":565,"hasResults":11,"nctId":566,"briefTitle":567,"officialTitle":568,"acronym":569,"eligibilityCriteria":570,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":571,"enrollmentInfo":572,"targetDuration":4,"studyType":326,"phases":4,"briefSummary":573,"conditions":574,"keywords":579,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":582,"lastUpdatePostDateStruct":583,"startDateStruct":585,"completionDateStruct":587,"leadSponsor":589,"locationsCount":591},"100369811","registry-of-subjects-at-risk-of-pancreatic-cancer-100369811","NCT04095195","Registry of Subjects at Risk of Pancreatic Cancer","Italian Registry of Families At Risk of Pancreatic Cancer","IRFARPC","Inclusion Criteria to enter the registry:\n\n* individuals with at least two relatives suffering from pancreatic cancer, with at least 1 first-degree and until the third-degree\n* subjects with known genetic mutation of BRCA2, BRCA1, p16, PALB2 with at least 1 first- or 2nd-degree relative suffering from pancreatic cancer\n* subjects suffering from FAMMM Syndrome\n* subjects suffering from Peutz-Jeghers Syndrome\n* subjects suffering from PRSS-1- or CFTR- or SPINK-1- related pancreatitis\n* subjects suffering from Lynch syndrome with at least 1 first- or 2nd-degree relative suffering from pancreatic cancer\n\nInclusion criteria to join the \"radiologic follow-up\":\n\n* 45 years or 10 years younger than the youngest index case of pancreatic cancer in the family for familial cases\n* 40 years or 5 years younger than the youngest index case of pancreatic cancer for subjects suffering from hereditary\u002Fgenetic pancreatitis, Lynch syndrome, or carrying a known BRCA 1\u002F2, PALB2, p16 genetic mutation with familiarity for pancreatic cancer\n* 30 years for subjects suffering from FAMMM, Peutz-Jeghers syndrome\n\nExclusion Criteria:\n\n\\- pregnancy","80 Years",{"count":422,"type":20},"IRFARPC is a multicenter national registry designed to study the diagnosis and predisposing factors of subjects with an inherited increased risk for pancreatic cancer.",[575,27,28,335,576,577,578],"Familial Pancreatic Cancer","FAMMM - Familial Atypical Mole Malignant Melanoma Syndrome","Hereditary Pancreatitis","Peutz-Jeghers Syndrome",[575,59,335,580,581],"Screening pancreatic cancer","Surveillance pancreatic cancer","2023-01-12",{"date":584,"type":39},"2023-01-13",{"date":586,"type":39},"2019-08-20",{"date":588,"type":20},"2045-09-20",{"name":590,"class":46},"Associazione Italiana per lo Studio del Pancreas",4]