pamiparib in mcrpc with hrd or brca1/2 mutation

Conditions: Metastatic Castration-resistant Prostate Cancer

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.

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.

Eligibility criteria:
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

Keywords: metastatic castration-resistant prostate cancer parp inhibitor homologous recombination deficiency brca1/2 mutation