A Study of Talazoparib in Men With DNA Repair Defects and Metastatic Castration-Resistant Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Talazoparib
Intervention description: 1 mg daily
Intervention MeSH terms: Talazoparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 128.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this international, phase 2, open-label, response rate study of talazoparib is
      to assess the efficacy and safety of talazoparib in men with DNA repair defects metastatic
      castration-resistant prostate cancer (CRPC) who previously received taxane-based chemotherapy
      and progressed on at least 1 novel hormonal agent (enzalutamide and/or abiraterone
      acetate/prednisone).
    

Eligibility criteria:

        Inclusion Criteria:

          1. At least 18 years of age.

          2. Histologically or cytologically confirmed adenocarcinoma of the prostate without
             signet cell, or small cell features.

          3. Patients must have measurable soft tissue disease per RECIST 1.1

          4. DNA damage repair deficiency as assessed centrally by a gene mutation biomarker panel
             (testing of de novo or archival tumor tissue (via central laboratory) or prior
             historical testing (with Sponsor approval) using the Foundation Medicine,
             FoundationOne CDx™ NGS gene panel test.

          5. Consent to a saliva sample collection for a germline comparator, unless prohibited by
             local regulations or ethics committee (EC) decision.

          6. Serum testosterone ≤ 1.73 nmol/L (50 ng/dL) at screening.

          7. Bilateral orchiectomy or ongoing androgen deprivation therapy with a
             gonadotropin-releasing hormone (GnRH) agonist/antagonist (surgical or medical
             castration).

          8. Progressive disease at study entry defined as 1 or more of the following 3 criteria:

               -  A minimum of 3 rising PSA values with an interval of at least 1 week between
                  determinations. The screening central laboratory PSA value must be ≥ 2 μg/L (2
                  ng/mL) if qualifying solely by PSA progression.

               -  Soft tissue disease progression as defined by RECIST 1.1.

               -  Bone disease progression defined by PCWG3 with 2 or more new metastatic lesions
                  on bone scan.

          9. Metastatic disease.

         10. Previous treatment with 1 or 2 chemotherapy regimens including at least 1 taxane-based
             regimen for metastatic (non castrate or castrate) prostate cancer. Patients may have
             received radium-223 and/or cabazitaxel, or were deemed unsuitable, declined, or did
             not have access to these therapies.

         11. Documented disease progression (either radiographic or biochemical) on at least 1
             novel hormonal therapy (enzalutamide and/or abiraterone acetate/prednisone) for the
             treatment of metastatic CRPC, irrespective of prior NHT treatment for non castrate
             prostate cancer or nonmetastatic (M0) CRPC.

         12. Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before
             day 1 for patients receiving these therapies.

         13. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

         14. Estimated life expectancy of ≥ 6 months as assessed by the investigator.

         15. Able to swallow the study drug, have no known intolerance to study drugs or
             excipients, and comply with study requirements.

         16. Must use a condom when having sex from the time of the first dose of study drug
             through 4 months after last dose of study drug. A highly effective form of
             contraception must be used from the time of the first dose of study drug through 4
             months after last dose of study drug when having sex with a non pregnant female
             partner of childbearing potential.

         17. Must agree not to donate sperm from the first dose of study drug to 4 months after the
             last dose of study drug.

         18. Patients must be willing and able to comply with scheduled visits, treatment plan,
             laboratory tests and other study procedures.

        Exclusion Criteria:

          1. 1. Use of systemic chemotherapeutic (including but not limited to taxanes), hormonal,
             biologic, or radionuclide therapy for treatment of metastatic prostate cancer (other
             than approved bone targeting agents and GnRH agonist/antagonist) or any other
             investigational agent within 4 weeks before day 1.

          2. Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone chemotherapy.
             Patients who discontinued prior platinum based chemotherapy <=6 months prior to
             screening or whose disease previously progressed on platinum based therapy at any time
             in the past are also excluded.

          3. Treatment with any concurrent cytotoxic chemotherapy or investigational drug(s) within
             4 weeks or 5 half lives of the drug (whichever is longer) before Day 1 and/or during
             study participation

          4. Radiation therapy within 3 weeks (within 2 weeks, if single fraction of radiotherapy)
             before day 1.

          5. Major surgery within 2 weeks before day 1.

          6. Clinically significant cardiovascular disease.

          7. Significant renal, hepatic, or bone marrow organ dysfunction.

          8. Known or suspected brain metastasis or active leptomeningeal disease.

          9. Symptomatic or impending spinal cord compression or cauda equina syndrome.

         10. Prior diagnosis of myelodysplastic syndrome or acute myeloid leukemia

         11. History of another cancer within 3 years before enrollment with the exception of
             nonmelanoma skin cancers, or American Joint Committee on Cancer stage 0 or stage 1
             cancer that has a remote probability of recurrence in the opinion of the investigator
             and the sponsor.

         12. Gastrointestinal disorder affecting absorption.

         13. Current or anticipated use within 7 days prior to first dose of study drug or
             anticipated use during the study of the following P gp inhibitors (amiodarone,
             carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin,
             indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine,
             ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, verapamil, and valspodar).

         14. Any other acute or chronic medical or psychiatric condition (concurrent disease,
             infection, or comorbidity) that interferes with ability to participate in the study,
             causes undue risk, or complicates the interpretation of data, in the opinion of the
             investigator or sponsor, including recent (within the past year) or active suicidal
             ideation or behavior or laboratory abnormality that may increase the risk associated
             with study participation or investigational product administration or may interfere
             with the interpretation of study results and, in the judgment of the investigator,
             would make the patient inappropriate for entry into this study.

         15. Investigator site staff members directly involved in the conduct of the study and
             their family members, site staff members otherwise supervised by the investigator, or
             patients who are Pfizer employees, including their family members, directly involved
             in the conduct of the study.

         16. Fertile male subjects who are unwilling or unable to use a highly effective method of
             contraception as outlined in this protocol for the duration of the study and for at
             least 4 months after the last dose of investigational product.