Purpose

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

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Male
Accepts Healthy Volunteers
No

Inclusion Criteria

  • HRR gene alteration (as identified by the sponsor's required assays) as follows: 1. Cohort 1: positive for HRR gene alteration 2. Cohort 2: not positive for DRD (that is, HRR gene alteration) 3. Cohort 3: eligible by HRR status - Metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) - 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 bilateral orchiectomy - 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 (that is, novel second-generation AR-targeted therapy such as enzalutamide, apalutamide, or darolutamide; taxane-based chemotherapy, or more than 4 months of abiraterone acetate plus prednisone [AAP] prior to randomization) in the metastatic castration-resistant prostate cancer (mCRPC) setting; or AAP outside of the mCRPC setting - 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort 1: Participants with mCRPC and HRR Gene Alteration
Participants with L1 metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alteration will receive combination of niraparib 200 milligrams (mg) or matching placebo and abiraterone acetate (AA) 1000 mg plus prednisone 10 mg. In the open label extension (OLE) phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.
  • Drug: Niraparib
    Participants will receive niraparib 200 mg capsules once daily.
    Other names:
    • JNJ-64091742
  • Drug: Abiraterone Acetate
    Participants will receive AA 1000 mg tablets once daily.
  • Drug: Prednisone
    Participants will receive prednisone 10 mg tablets daily.
  • Drug: Placebo
    Participants will receive matching placebo once daily.
Experimental
Cohort 2: Participants with mCRPC and No HRR Gene Alteration
Participants with L1 mCRPC and no HRR Gene alteration will receive combination of niraparib 200 mg or matching placebo and AA 1000 mg plus prednisone 10 mg. In the OLE phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.
  • Drug: Niraparib
    Participants will receive niraparib 200 mg capsules once daily.
    Other names:
    • JNJ-64091742
  • Drug: Abiraterone Acetate
    Participants will receive AA 1000 mg tablets once daily.
  • Drug: Prednisone
    Participants will receive prednisone 10 mg tablets daily.
  • Drug: Placebo
    Participants will receive matching placebo once daily.
Experimental
Cohort 3 (Open-label): Participants with mCRPC
Participants with mCRPC will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets plus prednisone 10 mg.
  • Drug: Prednisone
    Participants will receive prednisone 10 mg tablets daily.
  • Drug: New Formulation of Niraparib and Abiraterone Acetate (AA)
    Participants will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets once daily.

Recruiting Locations

More Details

Status
Recruiting
Sponsor
Janssen Research & Development, LLC

Study Contact

Study Contact
844-434-4210
JNJ.CT@sylogent.com

Detailed Description

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 tumors. In participants with metastatic prostate cancer, DNA-repair anomalies are identified in approximately 15 percent (%) to 20% of tumors. The study will consist of 5 phases: a prescreening phase for biomarker evaluation only, a screening phase, a treatment phase, a follow up phase, and an extension phase (either open-label extension [OLE] or long-term extension [LTE]). 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.