A Study of the Drugs Talazoparib and Temozolomide in Prostate Cancer

Inclusion Criteria

• •Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information or have their legally authorized representative provide written informed consent. A signed informed consent must be obtained prior to performing screening procedures.
• •NOTE: HIPAA authorization may be either included in the informed consent or obtained separately
• •Males 18 years of age or above
• •Histologically or cytologically confirmed adenocarcinoma of the prostate
• •Bilateral orchiectomy or ongoing androgen deprivation therapy with a GnRH agonist/antagonist (surgical or medical castration)
• •Progression of mCRPC on treatment with at least 1 second generation hormonal agent (e.g., enzalutamide and/or abirateroneacetate/prednisone)
• •Documented progressive mCRPC based on at least one of the following criteria:
• •* PSA progression defined as at least 2 rises in PSA with a minimum of a 1-week interval
• •* 1.0 ng/mL is the minimal starting value if confirmed rise is only indication of progression
• •* Soft-tissue progression per RECISTv1.1
• •* Progression of bone disease (evaluable disease) or tow or more new bone lesions by bone scan
• •Metastatic disease documented by bone lesions on whole-body radionuclide bone scan or soft tissue disease by computed tomography/magnetic-resonance imaging (CT/MRI).
• •Consent to a fresh tumor biopsy during screening or have sufficient archival tumor tissue available for molecular profile and biomarker analyses
• •ECOG status of 0 or 1 (Appendix A: Performance Status Criteria)
• •Serum testosterone \</= 50mg/dL at screening
• •Adequate organ function with acceptable initial laboratory values within 14 days of treatment start:
• •Absolute neutrophil count (ANC): \>/= 1,500/ul Hemoglobin: \>/= 9g/dL Platelet count: \>/= 100,00/ul Creatinine: \>/= 60 mL/min estimated using the Cockcroft-Gault equation Potassium: \>/= 3.5 mmol/L (within institutional normal range) Bilirubin: \</= 1.5 ULN (unless documented Gilbert's disease) SGOT(AST): \</= 2.5 x ULN SGPT (ALT): \</= 2.5 x ULN
• •Patients must agree to use a highly effective method of contraception (e.g., spermicide in conjunction with a barrier such as a condom) or sexual abstinence during treatment, and for at least 7 months after completing therapy. Furthermore, male patients with female partners of reproductive potential and pregnant partners must use a condom (even after vasectomy), during treatment and for at least 4 months after the final dose. Sperm donation is prohibited during the study and for 30 days after the last dose of study drug. Female partners must use hormonal or barrio contraception unless postmenopausal or abstinent.