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

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

Inclusion Criteria

• Deoxyribonucleic acid (DNA)-repair gene defects (DRD) status (as identified by the sponsor's required assays) as follows:
• Cohort 1: positive for DRD
• Cohort 2: not positive for DRD (i.e. No DRD)
• Metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI)
• Progression of metastatic prostate cancer in the setting of castrate levels of testosterone less than or equal to (<=) 50 nanogram per deciliter (ng/dL) on a gonadotropin releasing hormone analog (GnRHa), or history of bilateral orchiectomy at study entry as evidenced by prostate-specific antigen (PSA) progression or radiographic progression
• Able to continue GnRHa during the study if not surgically castrate
• Score of <= 3 on the brief pain inventory-short form (BPI-SF) question number 3 (worst pain in last 24 hours)

Exclusion Criteria

• Prior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor
• Systemic therapy (example, enzalutamide, docetaxel) in the metastatic castration-resistant prostate cancer (mCRPC) setting with the exception of less than 4 months of abiraterone acetate-Prednisone (AA-P) prior to randomization
• Symptomatic brain metastases
• History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
• Other prior malignancy (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) <= 2 years prior to randomization, or malignancy that currently requires active systemic therapy

This study will assess efficacy and safety of niraparib in combination with AA-P for the treatment of participants with metastatic 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 17α-hydroxylase/C17,20-lyase (CYP17), which is found in the testes and adrenals, as well as in prostate tissues and tumors. In participants with metastatic prostate cancer, DNA-repair gene defects (DRD) are identified in approximately 15 percent (%) to 20% of tumors. The study will consist of 4 phases: a prescreening phase for biomarker evaluation only, a screening phase, a double-blind treatment phase, and a follow up phase. During the prescreening phase participants will be evaluated for DRD 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 up to 73 months.

Lead Organization
Janssen Research & Development, LLC

Primary ID CR108534
Secondary IDs NCI-2019-03801, 64091742PCR3001, 2017-003364-12
Clinicaltrials.gov ID NCT03748641