Pamiparib in mCRPC With HRD or BRCA1/2 Mutation

Overview

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.

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