A Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer

Status: Active


The purpose of this study is to establish the recommended phase 2 dose (RP2D) of niraparib combination therapies of Part 1 and to evaluate the antitumor activity and safety of niraparib combination therapies of Part 2.

Eligibility Criteria

Inclusion Criteria

  • Participants willing to undergo all protocol-specified biopsies
  • Diagnosis of prostate adenocarcinoma as confirmed by the investigator Combination 1:
  • Must have determination of biomarker (BM) status for DNA-repair gene defects (DRD) (either BM positive [+] or BM negative [-]) by the sponsor's blood or tissue assay
  • Participants must have measurable disease as defined by response evaluation criteria in solid tumors (RECIST) 1.1 (soft tissue lesion of greater than or equal to (>=) 10 millimeter (mm) in the long axis or extrapelvic lymph node of >=15 mm in the short axis)
  • Must have previously received at least 1, but no more than 2, lines of novel androgen receptor (AR)-targeted therapy (that is, abiraterone acetate with prednisone, enzalutamide) for metastatic castration-resistant prostate cancer (mCRPC). Participants must have had at least 4 weeks of AR-targeted therapy Combination 2:
  • Must be biomarker positive for DRD by either the sponsor's blood or tissue assay
  • Must have progressed on 1 prior line of novel AR-targeted therapy (that is, abiraterone acetate with prednisone, enzalutamide) for mCRPC. Prior treatment with taxane-based therapy and AR-targeted therapy outside of the mCRPC setting is allowed

Exclusion Criteria

  • Prior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor
  • History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
  • Active malignancy (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently remission) less than or equal to (<=) 2 years prior to enrollment
  • Active infection requiring systemic therapy
  • Allergies, hypersensitivity, or intolerance to niraparib or the corresponding excipients

Locations & Contacts

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Name Not Available


Thomas Jefferson University Hospital
Status: Temporarily closed to accrual
Name Not Available

South Carolina

Medical University of South Carolina
Status: Active
Name Not Available


M D Anderson Cancer Center
Status: Active
Name Not Available


University of Wisconsin Hospital and Clinics
Status: Active
Name Not Available

Trial Objectives and Outline

This multicenter study will evaluate safety and efficacy of niraparib in combination with other anti-cancer agents. Two combinations are being studied: the first combination study will combine niraparib with the anti-programmed cell death protein (PD)-1 monoclonal antibody, JNJ-63723283 in participants with metastatic castration-resistant prostate cancer (mCRPC). The second combination will combine niraparib with abiraterone acetate plus prednisone (AA-P) in mCRPC participants with DNA-repair gene defects (DRD). Combination 1 has 2 parts: in Part 1 (dose selection), participants will be enrolled to explore 2 doses of niraparib and JNJ-63723283; and Part 2 (dose expansion) will evaluate the combination therapy in an expanded number of participants. In Part 2, participants will be enrolled into 2 cohorts based on biomarker status. Combination 2 has only 1 part (Part 2) and no Part 1. In Part 2, participants will be enrolled into 4 cohorts (breast cancer gene [BRCA] biallelic loss [2A], other DRD biallelic loss [2B], BRCA monoallelic loss [2C], and other DRD monoallelic loss [2D]). Each combination in the study will have 4 phases: A Prescreening Phase, a Screening Phase, a Treatment Phase, and a Follow-up Phase. Study evaluations will include efficacy, pharmacokinetic (PK), PK/pharmacodynamics, biomarkers, safety and tolerability.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type


Lead Organization

Lead Organization
Janssen Research & Development, LLC

Trial IDs

Primary ID CR108406
Secondary IDs NCI-2018-00392, 64091742PCR2002, 2017-003552-23
Clinicaltrials.gov ID NCT03431350