An Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies

Overview

The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of niraparib in men with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies.

Full Title of Study: “A Phase 2 Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 11, 2021

Detailed Description

This is a multicenter and open-label (participants and researchers are aware of the treatment that participants are receiving) study that consists of 4 phases: a Prescreening Phase for biomarker evaluation only, a Screening Phase, a Treatment Phase (Cycle 1 Day 1 and will continue until the study drug is discontinued), a Follow-up Phase (every 3 months after end of treatment visit), and a Long-term Extension Phase (until participants no longer derive benefit from treatment or until further notification on different means of study treatment). Participants will be monitored for safety during the study period, and up to 30 days after the last dose of study drug.

Interventions

  • Drug: Niraparib
    • Participants will receive 300 mg niraparib (3 capsules*100 mg) orally once daily.

Arms, Groups and Cohorts

  • Experimental: Niraparib
    • Participants will receive 300 milligram (mg) niraparib (3 capsules*100 mg) orally once daily.

Clinical Trial Outcome Measures

Primary Measures

  • Objective Response Rate (ORR)
    • Time Frame: Screening, Cycle 1 (each cycle of 28 days) Day 1 (every 8 weeks for the first 6 months and then every 12 weeks thereafter) till Follow-up Phase
    • ORR of soft tissue disease with no evidence of bone progression in participants with either biallelic Breast Cancer gene 1 (BRCA1) or Breast Cancer gene 2 (BRCA2) or germline BRCA. ORR in participants with measurable metastatic castration-resistant prostate cancer (mCRPC) and DNA-repair anomalies. ORR of soft tissue (visceral or nodal disease) as defined by RECIST 1.1 with no evidence of bone progression according to the Prostate Cancer Working Group 3 (PCWG3) criteria.

Secondary Measures

  • Objective Response Rate (ORR)
    • Time Frame: Up to 4 years and 6 months
    • ORR in participants with measurable metastatic castration-resistant prostate cancer (mCRPC) and DNA-repair anomalies. ORR of soft tissue (visceral or nodal disease) as defined by RECIST 1.1 with no evidence of bone progression according to the Prostate Cancer Working Group 3 (PCWG3) criteria.
  • Circulating Tumor Cells (CTC) Response
    • Time Frame: From Screening till End of Treatment (30 {+/- 5} days of last dose -up to 4 years and 6 months)
    • CTC response defined as CTC=0 per 7.5 milliliter (mL) blood at 8 weeks post-baseline in participants with baseline CTC greater than (>) 0.
  • Overall Survival (OS)
    • Time Frame: From enrollment to completion of study (up to 4 years and 6 months)
    • OS is defined as time from enrollment to death from any cause.
  • Radiographic Progression-Free Survival (rPFS)
    • Time Frame: From enrollment to completion of study (up to 4 years and 6 months)
    • rPFS is defined as time from enrollment to radiographic progression or death.
  • Time to Prostate Specific Antigen (PSA) Progression
    • Time Frame: From enrollment to completion of study (up to 4 years and 6 months)
    • First PSA increase that is 25 percent (%) or greater and an absolute increase of 2 nanogram/milliliter (ng/mL) or more above the nadir.
  • Time to Symptomatic Skeletal Event (SSE)
    • Time Frame: From enrollment to completion of study (up to 4 years and 6 months)
    • Time to SSE: time from enrollment to first symptomatic fracture, radiation or surgery to bone, or spinal cord compression.
  • Number of Participants With Adverse Events as a Measure of Safety and Tolerability
    • Time Frame: From enrollment to completion of study (up to 4 years and 6 months)
  • Duration of Objective Response
    • Time Frame: From complete response (CR) or partial response (PR) to radiographic progression of disease (up to 4 years 6 months)
    • Duration of objective response is defined as time from complete response or partial response to radiographic progression of disease, unequivocal clinical progression or death, whichever occurs first.

Participating in This Clinical Trial

Inclusion Criteria

  • Histologically confirmed prostate cancer (mixed histology is acceptable, with the exception of the small cell pure phenotype, which is excluded)
  • Received a taxane-based chemotherapy for the treatment of metastatic prostate cancer with evidence of disease progression on or after treatment, or discontinued from a taxane-based chemotherapy due to an adverse event
  • Received a second-generation or later androgen receptor (AR)-targeted therapy (for example, abiraterone acetate plus prednisone, enzalutamide, apalutamide) for the treatment of metastatic prostate cancer with evidence of disease progression or non-metastatic castration-resistant prostate cancer with evidence of subsequent metastasis
  • Biomarker-positive by at least one of the following criteria: (a) Biallelic deoxyribonucleic acid (DNA)-repair anomaly based on a sponsor validated blood or tissue assay; (b) Germline pathogenic Breast Cancer gene (BRCA) 1 or BRCA2 by any test (somatic local results must be confirmed as positive by the sponsor-validated assay before dosing)
  • Progression of metastatic prostate cancer in the setting of castrate levels of testosterone or history of bilateral orchiectomy at study entry

Exclusion Criteria

  • Prior treatment with a poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor
  • Prior platinum-based chemotherapy for the treatment of prostate cancer
  • Known history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
  • Symptomatic or impending cord compression
  • Symptomatic brain metastases

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Janssen Research & Development, LLC
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Janssen Research & Development, LLC Clinical Trial, Study Director, Janssen Research & Development, LLC

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