This is a biomarker preselected, randomized, open-label, multicenter, phase II study in men with metastatic castration resistant prostate cancer (mCRPC). Patients with tumors that have ATM, BRCA1 and/or BRCA2 mutations/deletions/loss of heterozygosity will be randomized in a 1:1:1 fashion to each arm. Patients with mutations in noncanonical DNA repair genes including FANCA, PALB2, RAD51, ERCC3, MRE11, NBN, MLH3, CDK12, CHEK2, HDAC2, ATR, PMS2, GEN1, MSH2, MSH6, BRIP1, or FAM175A defects will be assigned to Arm IV with single agent olaparib.
A Randomized Phase II Trial of Abiraterone, Olaparib, or Abiraterone + Olaparib in Patients With Metastatic Castration-Resistant Prostate Cancer With DNA Repair Defects
Prostate Cancer Metastatic Castration-Resistant Abnormal DNA Repair Metastatic Prostate Carcinoma Stage IV Prostate Cancer Prednisone Olaparib Abiraterone Acetate
Open to males ages 18 years and up
Documented progressive mCRPC based on at least one of the following criteria:
Agree to undergo a biopsy of at least one metastatic site to determine DNA repair defects. However:
Adequate organ function as defined below obtained within 14 days of registration:
ANC> or = 1500/µl Hemoglobin ≥ 10.0 g/dL WBC> 3x10^9/L Platelet count 100,000/µl Creatinine ≥51 mL/min estimated using the Cockcroft-Gault equation Potassium ≥ 3.5 mmol/L(within institutional normal range) Bilirubin within normal institutional limits (or <2X the upper limit of normal (ULN) in those with Gilbert's disease) AST (SGOT) / ALT (SGPT) ≤1.5x institutional ULN unless liver metastases are present in which case it must be ≤ 5x ULN
Note: Patients can receive a stable dose of bisphosphonates for bone metastases, including zoledronic acid, or denosumab before and during the study as deemed appropriate by the treating physician.
Note: Patients are not considered to have a "currently active" malignancy if they have completed all therapy and are now considered without evidence of disease for 1 year.
Patients must stop taking phenytoin, rifampicin, rifapentine, rifabutin,carbamazepine, nevirapine, modafinil and St John's Wort (Hypericum perforatum) 3 weeks prior to registration.
Patients must stop taking phenobarbitone 5 weeks prior to registration.
Patients must stop taking all strong CYP3A4 inhibitors, including clarithromycin,telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir,lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir, prior to registration.
We will not share your information with anyone other than the team in charge of this study. Submitting your contact information does not obligate you to participate in research.
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If you do not hear from the study team, please call 888-689-8273 and tell them you’re interested in study number NCT03012321.
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