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
• Part 2: Combination 2: Composite Response Rate (RR)
• 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 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)
• Part 2: Combination 2: Objective Response Rate (ORR)
• 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 will combine niraparib with abiraterone acetate plus prednisone (AA-P) in mCRPC participants with DNA-repair gene defects (DRD). Combination 3 will evaluate the relative bioavailability (BA) of niraparib and AA in combination. In a pharmacokinetics (PK) assessment phase, niraparib and AA will be administered, and in an extension phase, niraparib and AA-P will be administered. 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