Presurgical Phase II Study of Talazoparib in Combination With Enzalutamide in Prostate Cancer

Exclusion Criteria

• •1. Patients with biopsy-proven small cell or sarcomatoid histology.
• •2. Patients with clinical or radiological evidence of bone or other extranodal metastasis.
• •3. Patients who have had prior chemotherapy, experimental agents for prostate cancer, or patients receiving \>4 weeks of prior ADT will be excluded.
• •4. Treatment with estrogens, cyproterone acetate or glucocorticoids (at a dose \>10 mg/day of prednisone equivalent) in the 4 weeks prior to scheduled Day 1 of treatment.
• •5. Gastrointestinal abnormalities such as inability to take oral medication; requirement for intravenous alimentation; prior surgical procedures affecting absorption including total gastric resection; active gastrointestinal bleeding as evidenced by hematemesis, hematochezia, or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy; malabsorption syndromes.
• •6. History or current diagnosis of MDS/AML, and/or history of any malignancy \[other than the one treated in this study\] which has a ≥ 30% probability of recurrence within 24 months (except for adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix or Ta urothelial carcinoma).
• •7. Known hypersensitivity to recombinant proteins, or any excipient contained in the drug formulation for talazoparib and/or enzalutamide.
• •8. Congenital long QT syndrome or Electrocardiogram (ECG) at screening with QT interval corrected using Fridericia's formula (QTcF) \> 500 milliseconds.
• •9. Patients with any infectious process that, in the opinion of the investigator, could worsen or its outcome be affected as a result of the investigational therapy.
• •10. Patients with active or symptomatic viral hepatitis or chronic liver disease.
• •11. Patients with active pneumonitis or extensive bilateral lung disease of non-malignant etiology.
• •12. Patients with seizures or known condition that may pre-dispose to seizures (e.g., prior stroke or transient ischemic attack within 1 year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy).
• •13. Patients with symptomatic congestive heart failure, unstable angina or myocardial infarction, coronary/peripheral artery bypass graft or repair, clinically significant ventricular arrhythmias, deep vein thrombosis or pulmonary embolism in the 6 months prior to randomization.
• •14. Persistently uncontrolled diabetes mellitus or HIV infection.
• •15. Inadequately controlled hypertension (defined as systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>95 mmHg) despite antihypertensive medication, or prior history of hypertensive encephalopathy.
• •16. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
• •17. Anticipation of need for major surgical procedure during the course of the study other than as outlined by the protocol.
• •18. History of abdominal fistula or gastrointestinal perforation within 6 months prior to randomization.
• •19. Overt psychosis, mental disability, otherwise incompetent to give informed consent, or history of non-compliance.
• •20. Planned participation in any other experimental drug study.