This phase II trial studies how well berzosertib (M6620) and carboplatin with or without docetaxel works in treating patients with castration-resistant prostate cancer that has spread to other places in the body (metastatic). M6620 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving M6620, carboplatin and docetaxel may work better in treating patients with metastatic castration-resistant prostate cancer compared to carboplatin and docetaxel alone.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
73
City of Hope Comprehensive Cancer Center
Duarte, California, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, United States
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, United States
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, United States
Yale University
New Haven, Connecticut, United States
...and 13 more locations
Overall Response Rate
Defined by radiographic response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or prostate specific antigen \[PSA\] response (\> 50% decline from baseline).
Time frame: Radiologic measurements are performed every 3 cycles Up to 2 years. PSA measurements are performed every cycle up to 2 years
Progression-free Survival (PFS)
Assessed by Prostate Cancer Working Group (PCWG) 3 criteria. PFS to be estimated with the Kaplan Meier methodology. Median will be provided with 95% confidence interval.
Time frame: From the time of randomization up to 2 years
Time to PSA Progression
Assessed by PCWG2. PSA progression will be estimated with the Kaplan Meier methodology. Median will be provided with 95% confidence interval.
Time frame: From the time of randomization up to 2 years
Radiographic Progression-free Survival (rPFS)
Assessed by RECIST 1.1 for non-osseous disease and by PCWG3 for osseous disease. rPFS will be estimated with the Kaplan Meier methodology. Median will be provided with 95% confidence interval.
Time frame: From the time of randomization up to 2 years
Incidence of Adverse Events
Adverse events will be graded and analyzed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: Up to 2 years (from treatment initiation to 30 days after the last dose of study treatment)
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