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

Official Title

A Phase 1b-2 Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer

Summary:

The purpose of this study is to: a) establish the recommended phase 2 dose (RP2D) and to evaluate the antitumour activity and safety of niraparib combination therapies (Combinations 1 and 2) and b) to determine the relative bioavailability of niraparib and abiraterone acetate (AA) in combination (Combination 3) in participants with metastatic castration-resistant prostate cancer (mCRPC).

Trial Description

Primary Outcome:

  • Part 1: Combination 1: Incidence of Specified Toxicities
  • Part 2: Combination 1: Objective Response Rate (ORR)
  • Part 2: Combinations 1: Incidence of Adverse Events (AEs)
  • Part 2: Combinations 1: Severity of Adverse Events
  • Combination 3: Maximum Observed Analyte Plasma Concentration (Cmax) of Niraparib and AA After a Single Dose
  • Combination 3: Maximum Observed Analyte Plasma Concentration for Niraparib Normalized by the Dose (Cmax/dose) of Niraparib and AA After a Single Dose
  • Combination 3: Area Under the Plasma Concentration-Time Curve from Time Zero to 168 Hours (AUC [0-168]) of Niraparib and AA After a Single Dose
  • Combination 3: Area Under the Plasma Concentration-Time Curve for Niraparib from Time Zero to 168 Hours (AUC [0-168]/dose) of Niraparib and AA After a Single Dose
Secondary Outcome:
  • Part 1 and Part 2 (Combination 1): Plasma Concentrations of Niraparib and Cetrelimab
  • Part 1 and Part 2 (Combination 1): Number of participants with Anti-Drug Antibodies
  • Part 2: Combination 1: Number of Participants with Circulating Tumour Cell (CTC) Response
  • Part 2: Combination 1: Composite Response Rate (RR)
  • Part 2: Combination 1: Duration of Objective Response
  • Part 2: Combination 1: Overall Survival (OS)
  • Combination 3: Number of Participants with Adverse Events
  • Combination 3: Number of Participants with Abnormal Clinical Laboratory Findings
This multicentre study will evaluate safety and efficacy of niraparib in combination with other anti-cancer agents. Combination 1 will combine niraparib with the anti-programmed cell death protein (PD)-1 monoclonal antibody cetrelimab, in participants with mCRPC. Combination 1 has 2 parts: in Part 1 (dose selection), participants will be enrolled to establish RP2D doses of niraparib and cetrelimab; and Part 2 (dose expansion) will evaluate the combination therapy in an expanded number of participants into 2 cohorts (biomarker positive or biomarker negative). Combination 2 is closed to enrollment. Combination 3 will evaluate the relative bioavailability (BA) of niraparib and AA in combination. In pharmacokinetics (PK) assessment phase niraparib will be administered in combination with AA and in extension phase niraparib plus AA will be administered in combination with prednisone. Combinations 1 and 2 will have 4 phases: A Pre-screening Phase, a Screening Phase, a Treatment Phase, and a Follow-up Phase; Combination 3 has 3 phases: A Screening Phase, A PK Assessment Phase, and an Extension Phase. Study evaluations will include efficacy, PK, PK/pharmacodynamics, biomarkers, safety and tolerability.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society