[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"palb2-gene-mutation\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:palb2-gene-mutation":30},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,5,0,[8,48,73,140,170],{"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":57,"briefSummary":58,"conditions":59,"keywords":62,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":65,"lastUpdatePostDateStruct":66,"startDateStruct":68,"completionDateStruct":70,"leadSponsor":71,"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":56,"type":20},18,[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).",[27,28,60,30,61,29],"BRCA Mutation","Checkpoint Kinase 2 Gene Mutation",[63,64],"Homologous Recombination Deficiency","HRR Pathway","2026-05-22",{"date":67,"type":39},"2026-05-27",{"date":69,"type":39},"2024-02-07",{"date":43,"type":20},{"name":72,"class":46},"Varun Monga, MBBS",{"id":74,"slug":75,"hasResults":11,"nctId":76,"briefTitle":77,"officialTitle":78,"acronym":79,"eligibilityCriteria":80,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":81,"targetDuration":4,"studyType":21,"phases":82,"briefSummary":83,"conditions":84,"keywords":102,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":129,"lastUpdatePostDateStruct":130,"startDateStruct":132,"completionDateStruct":134,"leadSponsor":136,"locationsCount":139},"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.",[85,27,28,86,87,88,89,90,91,92,93,94,95,96,30,97,98,99,100,101],"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",[103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128],"pancreatic adenocarcinoma","pancreatic cancer","BRCA","BRCA1","BRCA2","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":131,"type":39},"2026-01-29",{"date":133,"type":39},"2021-01-13",{"date":135,"type":20},"2028-12",{"name":137,"class":138},"General Oncology, Inc.","INDUSTRY",2,{"id":141,"slug":142,"hasResults":11,"nctId":143,"briefTitle":144,"officialTitle":145,"acronym":146,"eligibilityCriteria":147,"healthyVolunteers":11,"sex":148,"minAge":17,"maxAge":4,"enrollmentInfo":149,"targetDuration":4,"studyType":151,"phases":4,"briefSummary":152,"conditions":153,"keywords":158,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":161,"lastUpdatePostDateStruct":162,"startDateStruct":164,"completionDateStruct":166,"leadSponsor":168,"locationsCount":47},"100446733","the-genpet-study---an-imaging-study-of-fch-pet-ct-in-men-with-prostate-cancer-and-a-dna-repair-gene-mutation-100446733","NCT05097274","The GENPET Study - An Imaging Study of FCH-PET-CT in Men With Prostate Cancer and a DNA Repair Gene Mutation.","An Imaging Study of FCH-PET-CT in Men With Prostate Cancer and a DNA Repair Gene Mutation (GENPET)","GENPET","Inclusion Criteria:\n\n* Confirmed pathogenic germline mutation in any of the following genes BRCA1, BRCA2, MSH2, MSH6, MLH1, PMS2, CHEK2, PALB2 or ATM.\n* Over the age of 18\n* Diagnosed with prostate cancer and at a time when staging imaging is clinically indicated; either:\n\n  * At a new diagnosis\n  * Biochemically progressing patients who were treated radically with surgery or radiotherapy (more than 6 months ago) and are currently not receiving hormonal treatment or chemotherapy\n  * Patients on active surveillance with a PSA doubling time of 6 months or less\n\nExclusion Criteria:\n\n* Diagnosis of other malignancy (excluding basal cell cancer\u002Fsquamous cell cancer of the skin) within five years of diagnosis\n* Known metastatic prostate cancer, both local and distant\n* Patients who have received any oncological treatment within the last six months\n* Patients on any investigational drug treatment\n* Patients on steroids\n* Known history of inflammatory\u002Finfective diseases (e.g. sarcoidosis, tuberculosis, inflammatory bowel disease)\n* Contraindications to having an MRI using the standard MRI checklist (e.g. pacemakers, aneurysm clips, claustrophobia)","MALE",{"count":150,"type":20},50,"OBSERVATIONAL","The aim of the study is to determine if PET-CT imaging (using contrast recommended in clinical guidelines) is superior to combined bone scan and MRI\u002FCT of the abdomen \\& pelvis in detecting the increased incidence of metastasis (nodal\u002Fdistant outside the pelvis) in men with prostatic carcinoma with mutations in any of the following germline DNA repair genes BRCA1, BRCA2, MSH2, MSH6, MLH1, PMS2, CHEK2, PALB2, ATM.",[154,60,155,29,156,157,30],"Prostate Cancer","Mismatch Repair Gene Mutation","HOXB13 Germline Mutation","CHEK2 Gene Mutation",[159,160],"FCH-PET-CT","PSMA-PET-CT","2025-12-08",{"date":163,"type":39},"2025-12-16",{"date":165,"type":39},"2015-10-15",{"date":167,"type":20},"2032-12-31",{"name":169,"class":46},"Institute of Cancer Research, United Kingdom",{"id":171,"slug":172,"hasResults":11,"nctId":173,"briefTitle":174,"officialTitle":175,"acronym":4,"eligibilityCriteria":176,"healthyVolunteers":177,"sex":16,"minAge":178,"maxAge":4,"enrollmentInfo":179,"targetDuration":4,"studyType":21,"phases":181,"briefSummary":183,"conditions":184,"keywords":202,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":207,"lastUpdatePostDateStruct":208,"startDateStruct":210,"completionDateStruct":212,"leadSponsor":214,"locationsCount":215},"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",true,"25 Years",{"count":180,"type":20},1000,[182],"NA","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.\"",[27,185,186,28,187,188,29,189,190,191,192,193,157,194,30,195,196,197,198,199,200,201],"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",[203,204,205,206],"EfFORT","Memorial Sloan Kettering Cancer Center","Genetic Testing","22-023","2025-11-10",{"date":209,"type":39},"2025-11-12",{"date":211,"type":39},"2022-12-01",{"date":213,"type":20},"2026-11-30",{"name":204,"class":46},8]