Treatment of Metastatic Castration-Resistant Prostate Cancer With Homologous Recombination Deficiency

Phase 2TerminatedNCT03712930

BeiGene13 enrolled

Overview

This study is designed to evaluate the efficacy of pamiparib in participants with metastatic castration-resistant prostate cancer (mCRPC) positive for circulating tumor cells (CTC) with homologous recombination deficiency (CTC-HRD). All participants will receive pamiparib. The purpose of this study is to demonstrate that pamiparib will improve Objective Response Rate (ORR) and Prostate-Specific Antigen (PSA) response rate

This is a global, Phase 2, open-label study of pamiparib in approximately 100 participants with metastatic castration-resistant prostate cancer (mCRPC) positive for circulating tumor cells (CTC) with homologous recombination deficiency (CTC-HRD). Participants in Cohort 1 will include 50 mCRPC participants with CTC-HRD-positive, measurable metastatic disease (soft tissue with/without bone lesions), and positive BRCA1/2 mutation or negative/unknown BRCA1/2 mutation. Cohort 2 will include 30 mCRPC CTC-HRD positive participants with bone metastasis only and positive or negative/unknown BRCA1/2. Cohort 3 and 4 will include 20 mCRPC CTC-HRD negative/unknown participants with BRCA1/2 positive mutations, metastatic disease (measurable soft tissue with/without bone), and bone only. Participants will undergo PSA level assessments approximately every 4 weeks as well as tumor assessments every 8 weeks for 24 weeks and the every 12 weeks, or as clinically indicated. Administration of pamiparib will continue until disease progression, unacceptable toxicity, death or another discontinuation criterion is met.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Metastatic Castration-Resistant Prostate Cancer (mCRPC)Homologous Recombination Deficiency (HRD)

Interventions

PamiparibDRUG

60 mg orally twice daily (BID)

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Men (≥ 18 years of age) with histologically or cytologically confirmed adenocarcinoma or poorly differentiated adenocarcinoma of the prostate without neuroendocrine differentiation with HRD deficiency by CTC-HRD assay and/or deleterious germline or somatic mutation in BRCA1 or BRCA2; mCRPC measurable disease and/or bone disease. • PSA progression with ≥ 3 rising PSA levels with ≥ 1 week between determinations and a screening PSA ≥ 2 μg/L (2 ng/mL). * Must be surgically or medically castrated with serum testosterone levels of ≤1.73 nmol/L (50 ng/dL), must have received ≥ 1 prior androgen receptor-targeted therapy, and must have received ≥ 1 taxane-based therapy. * mCRPC with 1 or 2 of the following: * Measurable disease per RECIST v1.1 * Bone disease * CTC-HRD+ or BRCA1/2 mutation * PSA progression (PCWG3 criteria) * ≥1 androgen receptor-targeted therapy (eg, abiraterone acetate/prednisone or enzalutamide) for mCRPC with progressive disease * ≥1 taxane for metastatic prostate cancer Key Exclusion Criteria: * Chemotherapy, hormonal therapy, biologic therapy, radionuclide therapy, immunotherapy, investigational agent, anticancer Chinese medicine, or herbal remedies ≤ 5 half-lives if the half-life is known, ≤ 14 days if not known, before start of study treatment * Continued treatment with a bisphosphonate or denosumab is allowed, if administered at a stable dose \> 28 days before start of study treatment * Radiotherapy ≤ 21 days (≤ 14 days, if single fraction of radiotherapy) before start of study treatment Prior treatment for prostate cancer with any of the following: * poly ADP ribose polymerase (PARP) inhibitor * Platinum * Cyclophosphamide * Mitoxantrone NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (9)

University Cancer and Blood Center

Athens, Georgia, United States

Montefiore Einstein Cancer Center

The Bronx, New York, United States

University of Washington

Seattle, Washington, United States

Gosford Hospital

Outcomes

Primary Outcomes

Objective Response Rate (ORR) Determined by Independent Review Committee

ORR is the percentage of participants with a best objective response of complete response (CR) or partial response (PR) confirmed at a subsequent timepoint ≥ 4 weeks later by an Independent Review Committee (IRC).

Time frame: Up to 1 year and 6 months

Prostate-Specific Antigen (PSA) Response Rate

PSA response rate is defined as the percentage of participants with PSA decline ≥ 50% from baseline \[confirmed by a second PSA value ≥ 3 weeks later\] for CTC-HRD-positive participants with or without measurable disease.

Time frame: Up to 1 year and 6 months

Secondary Outcomes

Duration of Response (DOR) by IRC

DOR is defined as the time from the date of the earliest documented CR or PR (that is subsequently confirmed) to radiographic disease progression or death due to any cause, whichever occurs first.

Time frame: Up to 1 year and 7 months

Objective Response Rate by Investigator

ORR is the percentage of participants with a best objective response of complete response (CR) or partial response (PR) confirmed at a subsequent timepoint ≥ 4 weeks later by the investigator.

Time frame: Up to 1 year and 6 months

Time to Objective Response by Investigator

Time to objective response is defined as the time from the date of the first dose of study drug to the first documented confirmed response of CR or PR assessed by the investigator and summarized for participants who have achieved a confirmed objective response.

Time frame: Up to 1 year and 6 months

Clinical Benefit Rate By Investigator

Clinical Benefit Rate is the percentage of participants who achieved confirmed CR, PR, or SD or NON-CR/NON-PD. The minimum interval for confirmed CR and PR is 4 weeks and the measurement of SD or NON-CR/NON-PD is 7 weeks after first dose date.

Data from ClinicalTrials.gov

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