M6620 and Carboplatin With or Without Docetaxel in Treating Patients With Metastatic Castration-Resistant Prostate Cancer

PRIMARY OBJECTIVE: I. To assess the difference in response rate (either achievement of prostate specific antigen \[PSA\] reduction of greater than 50% or radiographic response by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) of the combination of berzosertib (M6620) (VX-970, berzosertib) and carboplatin as compared to the combination of docetaxel and carboplatin. SECONDARY OBJECTIVES: I. To assess the difference in time to PSA progression by Prostate Cancer Working Group (PCWG)2 criteria of the combination of M6620 (VX-970, berzosertib) and carboplatin as compared to the combination of docetaxel and carboplatin. II. To describe radiographic progression-free survival and progression-free survival by PCWG3 criteria in both arms of the study. III. Assess the relationship with homologous recombination deficiency (HRD) detected from baseline tumor biopsy with response to the combination of M6620 (VX-970, berzosertib) and carboplatin and the combination of docetaxel and carboplatin. IV. To describe the safety and adverse events from the combination of M6620 (VX-970, berzosertib) + carboplatin as well the combination of docetaxel + carboplatin. EXPLORATORY OBJECTIVES: I. Comparison of overall survival in the two arms of the study. II. Explore response rate, time to PSA progression, radiographic progression-free survival, and progression-free survival by PCWG3 criteria in patients who initially receive docetaxel + carboplatin after crossover to M6620 + carboplatin. III. To assess the relationship with homologous recombination deficiency (HRD) detected from baseline circulating free deoxyribonucleic acid (DNA) (cfDNA) with response to the combination of M6620 and carboplatin and the combination of docetaxel and carboplatin, and describe alterations seen in cfDNA (and optional tumor biopsy) at end of study. OUTLINE: Patients are randomized to 1 of 2 groups. ARM A (docetaxel, carboplatin): Patients receive docetaxel intravenously (IV) over 60 minutes and carboplatin IV over 30 minutes on day 1 or carboplatin alone on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients have PSA progression or radiographic progression may crossover to Arm B. ARM B (carboplatin, berzosertib): Patients receive carboplatin IV over 30 minutes on day 1 and berzosertib IV over 60-90 minutes on days 2 and 9. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up between 30-42 days.