A Single Arm, Open-label, Phase II Study to Assess the Efficacy of Pamiparib in Metastatic Castration-Resistant Prostate Cancer Patients With Homologous Recombination Deficiency (HRD) or BRCA1/2 Mutation

Sun Yat-sen University1 site in 1 country50 target enrollmentMay 1, 2022

ConditionsMetastatic Castration-resistant Prostate Cancer

InterventionsPamiparib

DrugsPamiparib

Overview

Phase: Phase 2
Intervention: Pamiparib
Conditions: Metastatic Castration-resistant Prostate Cancer
Sponsor: Sun Yat-sen University
Enrollment: 50
Locations: 1
Primary Endpoint: Radiologic Progression-free Survival (rPFS)
Status: Recruiting
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to assess the efficacy of a PARP inhibitor, Pamiparib, in metastatic castration-resistant prostate cancer patients with homologous recombination deficiency or BRCA 1 or 2 somatic/germline mutation.

Detailed Description

This is a single arm, open-label, single center, phase II trial, assessing the efficacy of a PARP inhibitor, Pamiparib, in 50 progressing metastatic castration-resistant prostate cancer patients with at least one line of androgen deprivation therapy or chemotherapy at the metastatic setting, and homologous recombination deficiency or BRCA 1 or 2 somatic or germline mutation.

Registry

clinicaltrials.gov

Start Date

May 1, 2022

End Date

March 20, 2025

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Male

Investigators

Sponsor

Sun Yat-sen University

Responsible Party

Principal Investigator

ZHOU FANGJIAN

Professor

Sun Yat-sen University

Eligibility Criteria

Inclusion Criteria

•≥18 years old, male
•Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma without neuroendocrine differentiation of the prostate. Mixed histology is accepted, except for small cell carcinoma.
•Have a deleterious mutation in BRCA1/2 , or HRD score ≥
•Eastern Cooperative Oncology Group (ECOG) performance status ≤1
•Metastatic Castration-resistant Prostate Cancer (mCRPC): Presence of measurable target lesion according to RECIST criteria v1.1
•Male subject has been surgically or medically sterilized and has serum testosterone level ≤1.73nmol/L.
•Unsterilized male subject uses an acceptable method of contraception (defined as a barrier method with spermicide) to prevent pregnancy during the duration of the study and for 6 months after the last dose of Pamiparib.
•Experienced disease progression after having received at least 1 prior next-generation androgen receptor-targeted therapies, for metastatic castration-resistant disease.
•Capable of swallowing the whole capsule.
•Subjects must have normal organ and bone marrow function at baseline, as defined below:

Exclusion Criteria

•Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
•Acute toxicity (CTCAE \> grade 2) due to prior cancer therapy.
•Received chemotherapy, endocrine therapy, biotherapy, radionuclide therapy, immunotherapy, experimental drugs, proprietary anticancer drugs or Chinese herbal medicines within 5 (if known) half-lives or 14 days(if unknown) prior to the first day of taking Pamiparib; For bisphosphonates or approved bone targeting therapy, Pamiparib must be administered at a steady dose for ≥28 days prior to the first day of taking Pamiparib.
•Received radiation therapy within 21 days.
•Prior treatment with any PARP inhibitor. Prior chemotherapy with mitoxantrone or platinum-based chemotherapy or cyclophosphamide. Prior treatment with sipuleucel-T or immune check point inhibitors are allowed.
•Subjects with major surgery within 2 weeks before starting study treatment. Subjects expected to receive major surgery during the trial.
•Active second malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer
•Symptomatic and/or untreated central nervous system metastases
•Immunocompromised subjects, such as those with positive human immunodeficiency virus (HIV) serology.
•Subjects with known active hepatitis (e.g. hepatitis B or C).

Arms & Interventions

Pamiparib

Tablets 20mg per os : 40 mg / bid every day in continuous. Patients will be treated with Pamiparib. Cycles are defined in 28-day periods. Disease response will be assessed every 8 weeks (RECIST 1.1). Safety will be assessed continuously.

Intervention: Pamiparib

Outcomes

Primary Outcomes

Radiologic Progression-free Survival (rPFS)

Time Frame: 3 years

Radiologic progression-free survival will be assessed from the time of the first dose to radiologic disease progression or death from any cause, whichever comes first.

Secondary Outcomes

Objective Response Rate (ORR)(From enrollment to primary completion of study (up to approximately 3 years))
Duration of Response (DOR)(From enrollment to primary completion of study (up to approximately 3 years))
Clinical Benefit Rate(3 years)
Prostate Specific Antigen (PSA) Response Rate(From enrollment to primary completion of study (up to approximately 3 years))
Overall Survival (OS)(From enrollment to primary completion of study (up to approximately 3 years))
Adverse events(3 years)
Time to PSA Progression(From enrollment to primary completion of study (up to approximately 3 years))
Time to Response (TTR)(From enrollment to primary completion of study (up to approximately 3 years))