Pamiparib in mCRPC With HRD or BRCA1/2 Mutation

Metastatic Castration-resistant Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05327621
• Other study ID #: 2021-FXY-385
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2022
• Est. completion date: March 20, 2025

Study information

• Verified date: April 2022
• Source: Sun Yat-sen University
• Contact: Fangjian Zhou, M.D.
• Phone: 020-87343656
• Email: zhoufj[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: March 20, 2025
• Est. primary completion date: March 20, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Pamiparib
40 mg bid per os , 28 day cycle, number of cycles: until progression or unacceptable toxicity develops.

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Adverse events	Adverse events are graded according to the CTCAE V4.03	3 years