Pamiparib in mCRPC With HRD or BRCA1/2 Mutation
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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 Design
Arms and Interventions
| 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:
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Outcome Measures
Primary Outcome Measures
- Radiologic Progression-free Survival (rPFS) [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 Outcome Measures
- Objective Response Rate (ORR) [From enrollment to primary completion of study (up to approximately 3 years)]
Proportion of patients in complete remission (CR) plus partial remission (PR)
- Duration of Response (DOR) [From enrollment to primary completion of study (up to approximately 3 years)]
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.
- Time to Response (TTR) [From enrollment to primary completion of study (up to approximately 3 years)]
Time from initiation of treatment to first assessment of tumor as CR or PR.
- Clinical Benefit Rate [3 years]
according to RECIST, is either complete response (CR), partial response (PR) or stable disease (SD) lasting for at least 16 weeks
- Prostate Specific Antigen (PSA) Response Rate [From enrollment to primary completion of study (up to approximately 3 years)]
Proportion of patients with a 50% decrease in PSA from baseline
- Time to PSA Progression [From enrollment to primary completion of study (up to approximately 3 years)]
Time from initiation of treatment to two consecutive 50% PSA increases from baseline level
- Overall Survival (OS) [From enrollment to primary completion of study (up to approximately 3 years)]
Time between the start of treatment and death from any cause
- Adverse events [3 years]
Adverse events are graded according to the CTCAE V4.03
Other Outcome Measures
- rPFS stratified by baseline HRD score (HRD score threshold is defined as 9) [3 years]
The rPFS is defined as the duration from Pamiparib initiation to radiologic disease progression or death from any cause, whichever comes first.
- OS stratified by baseline HRD score (HRD score threshold is defined as 9) [3 years]
The OS is defined as the duration from Pamiparib initiation to any death.
Eligibility Criteria
Criteria
Inclusion Criteria:
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≥18 years old, male
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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.
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Have a deleterious mutation in BRCA1/2 , or HRD score ≥ 9.
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Eastern Cooperative Oncology Group (ECOG) performance status ≤1
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BPI<4
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Metastatic Castration-resistant Prostate Cancer (mCRPC): Presence of measurable target lesion according to RECIST criteria v1.1
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Male subject has been surgically or medically sterilized and has serum testosterone level ≤1.73nmol/L.
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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.
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Experienced disease progression after having received at least 1 prior next-generation androgen receptor-targeted therapies, for metastatic castration-resistant disease.
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Capable of swallowing the whole capsule.
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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 × 109/L. Platelet count ≥ 100 × 109/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.
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Agree to sign informed consent form
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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:
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Acute toxicity (CTCAE > grade 2) due to prior cancer therapy.
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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.
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Received radiation therapy within 21 days.
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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.
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Subjects with major surgery within 2 weeks before starting study treatment. Subjects expected to receive major surgery during the trial.
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Active second malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer
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Symptomatic and/or untreated central nervous system metastases
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Immunocompromised subjects, such as those with positive human immunodeficiency virus (HIV) serology.
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Subjects with known active hepatitis (e.g. hepatitis B or C).
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The subject has a serious cardiovascular disease. ( For example, but not limited to: uncontrolled arrhythmia, myocardial infarction)
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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.
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History of intolerance to Pamiparib capsule excipients
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Excluded by investigators
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sun Yat-sen University Cancer Center | Guangzhou | Guangdong | China | 510060 |
Sponsors and Collaborators
- Sun Yat-sen University
Investigators
- Principal Investigator: Fangjian Zhou, M.D., Sun Yat-sen University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021-FXY-385