A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer

Official Title

A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Subjects With Metastatic Prostate Cancer

Summary:

The purpose of this study is to evaluate the effectiveness of niraparib in combination with abiraterone acetate plus prednisone (AAP) compared to AAP plus placebo.

Trial Description

Primary Outcome:

• Cohort 1 and 3: Radiographic Progression Free Survival (rPFS)

Secondary Outcome:

• Cohort 1: Overall survival (OS)
• Cohort 1: Time to Symptomatic Progression
• Cohort 1: Time to Initiation of Cytotoxic Chemotherapy
• Cohort 1: Observed Plasma Concentrations of Niraparib
• Cohort 1: Observed Trough Plasma Concentrations of Abiraterone
• Cohort 1: Number of Participants with Treatment-Emergent Adverse events (TEAEs)
• Cohort 1: Number of Participants with Treatment-Emergent Adverse events by Severity
• Cohort 1: Number of Participants with Laboratory Abnormalities as Measure of Safety

This study will assess efficacy and safety of niraparib in combination with AAP for the treatment of participants with metastatic castration resistant prostate cancer. Niraparib is an orally available, highly selective poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, with potent activity against PARP-1 and PARP-2 deoxyribonucleic acid (DNA)-repair polymerases. AA is a pro-drug of abiraterone and selectively inhibits the enzyme 17 alpha-hydroxylase/C17,20-lyase (CYP17), which is found in the testes and adrenals, as well as in prostate tissues and tumours. In participants with metastatic prostate cancer, DNA-repair anomalies are identified in approximately 15 percent (%) to 20% of tumours. The study will consist of 4 phases: a prescreening phase for biomarker evaluation only, a screening phase, a treatment phase, and a follow up phase. During the prescreening phase participants will be evaluated for homologous recombination repair (HRR) gene alteration status and then will be assigned to one of the 2 cohorts based on their biomarker status. Treatment will be administered daily and is planned to be continuous until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. Efficacy, pharmacokinetics, biomarkers, participants reported outcomes and safety will be assessed. The total duration of study will be approximately 66 months.

View this trial on ClinicalTrials.gov