Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Abiraterone Acetate

Prednisone

Olaparib

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Abiraterone 1000 mg orally once daily and prednisone 5 mg orally twice daily, days 1-28 in 28 day cycles.

Olaparib 300 mg orally twice daily for days 1-28 in 28 day cycles.

Abiraterone 1000 mg orally once daily, prednisone 5 mg orally twice daily, olaparib 300 mg orally twice daily for days 1-28 in 28 day cycles.

Maha Hussain, MD, FACP, FASCO

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.

Abiraterone/Prednisone, Olaparib, or Abiraterone/Prednisone + Olaparib in Patients With Metastatic Castration-Resistant Prostate Cancer With DNA Repair Defects

BRCAAway: A Randomized Phase II Trial of Abiraterone, Olaparib, or Abiraterone + Olaparib in Patients With Metastatic Castration-Resistant Prostate Cancer With DNA Repair Defects

Evaluate the objective PFS of abiraterone/prednisone, olaparib or the combination abiraterone/prednisone + olaparib in mCRPC patients with canonical DNA repair defects in BRCA1, BRCA2, or ATM.

Objective disease response (complete response \[CR\] + partial response \[PR\]) assessed using RECIST 1.1.

PSA response rate (CR + PR) will be measured.

The rate of undetectable PSA (CR) will be measured.

Evaluate if noncanonical DNA repair defects have clinical susceptibility to PARP inhibition alone.

To evaluate the safety of the combination of abiraterone/prednisone + olaparib combination therapy. Adverse events will be assessed by the National Cancer Institute's CTCAE 4.0.

The response rate will be evaluated in patients who cross over to olaparib or abiraterone post progression on therapy with abiraterone or olaparib respectively by treatment arm.

The PFS will be evaluated in patients who cross over to olaparib or abiraterone post progression on therapy with abiraterone or olaparib respectively by treatment arm.

Adverse Event summaries will be reported by treatment arm and organized by body system, frequency of occurrence, intensity (i.e., severity grade), and causality or attribution. Treatment exposure will be summarized for all patients, including dose administration, number of cycles, dose modifications or delays, and duration of therapy.

Spots Global Cancer Trial Database for abnormal dna repair