Pamiparib in mCRPC With HRD or BRCA1/2 Mutation

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

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Pamiparib

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fangjian Zhou, M.D.; Phone Number: 020-87343656; Email: zhoufj@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Fangjian Zhou, M.D.; Phone Number: 020-87343656; Email: zhoufj@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. ≥18 years old, male
2. 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.
3. Have a deleterious mutation in BRCA1/2 , or HRD score ≥ 9.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
5. BPI<4
6. Metastatic Castration-resistant Prostate Cancer (mCRPC): Presence of measurable target lesion according to RECIST criteria v1.1
7. Male subject has been surgically or medically sterilized and has serum testosterone level ≤1.73nmol/L.
8. 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.
9. Experienced disease progression after having received at least 1 prior next-generation androgen receptor-targeted therapies, for metastatic castration-resistant disease.
10. Capable of swallowing the whole capsule.

11. Subjects must have normal organ and bone marrow function at baseline, as defined below:

    Hemoglobin ≥ 9.0 g/dL at least 28 days after transfusion . Absolute neutrophil count ≥ 1.5 × 10^9/L. Platelet count ≥ 100 × 10^9/L. Total bilirubin ≤ 1.5 × the upper limit of normal (ULN) specified. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase) ≤ 3 × the specified ULN, unless liver metastases are present, in which case it must be ≤ 5 × ULN.

12. Agree to sign informed consent form
13. Agree not to participate in other interventional trials during this trial.

Exclusion Criteria:

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

1. Acute toxicity (CTCAE > grade 2) due to prior cancer therapy.
2. 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.
3. Received radiation therapy within 21 days.
4. 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.
5. Subjects with major surgery within 2 weeks before starting study treatment. Subjects expected to receive major surgery during the trial.
6. Active second malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer
7. Symptomatic and/or untreated central nervous system metastases
8. Immunocompromised subjects, such as those with positive human immunodeficiency virus (HIV) serology.
9. Subjects with known active hepatitis (e.g. hepatitis B or C).
10. The subject has a serious cardiovascular disease. ( For example, but not limited to: uncontrolled arrhythmia, myocardial infarction)
11. Concomitant use of strong CYP3A inducers or moderate CYP3A inducers . If half-lives is known, a 5 half-lives washout period is required before the start of Pamiparib therapy and a 2-week washout period is required when the half-lives is unknown.
12. History of intolerance to Pamiparib capsule excipients
13. Excluded by investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Pamiparib; 40 mg bid per os , 28 day cycle, number of cycles: until progression or unacceptable toxicity develops.; Other Names: BGB-290

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiologic Progression-free Survival (rPFS)	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.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate	according to RECIST, is either complete response (CR), partial response (PR) or stable disease (SD) lasting for at least 16 weeks	3 years
Objective Response Rate (ORR)	Proportion of patients in complete remission (CR) plus partial remission (PR)	From enrollment to primary completion of study (up to approximately 3 years)
Duration of Response (DOR)	Time from the start of the first assessment of the tumor as CR or PR to the first assessment of PD (Progressive Disease) or death from any cause.	From enrollment to primary completion of study (up to approximately 3 years)
Time to Response (TTR)	Time from initiation of treatment to first assessment of tumor as CR or PR.	From enrollment to primary completion of study (up to approximately 3 years)
Prostate Specific Antigen (PSA) Response Rate	Proportion of patients with a 50% decrease in PSA from baseline	From enrollment to primary completion of study (up to approximately 3 years)
Time to PSA Progression	Time from initiation of treatment to two consecutive 50% PSA increases from baseline level	From enrollment to primary completion of study (up to approximately 3 years)
Overall Survival (OS)	Time between the start of treatment and death from any cause	From enrollment to primary completion of study (up to approximately 3 years)
Adverse events	Adverse events are graded according to the CTCAE V4.03	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
rPFS stratified by baseline HRD score (HRD score threshold is defined as 9)	The rPFS is defined as the duration from Pamiparib initiation to radiologic disease progression or death from any cause, whichever comes first.	3 years
OS stratified by baseline HRD score (HRD score threshold is defined as 9)	The OS is defined as the duration from Pamiparib initiation to any death.	3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2022
• Primary Completion (Anticipated): March 20, 2025
• Study Completion (Anticipated): March 20, 2025

Study Registration Dates

• First Submitted: March 27, 2022
• First Submitted That Met QC Criteria: April 7, 2022
• First Posted (Actual): April 14, 2022

Study Record Updates

• Last Update Posted (Actual): April 14, 2022
• Last Update Submitted That Met QC Criteria: April 7, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: PARP inhibitor; Metastatic Castration-resistant Prostate Cancer; Homologous Recombination Deficiency; BRCA1/2 Mutation
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 2021-FXY-385

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No