Talazoparib With Androgen Deprivation Therapy and Abiraterone for the Treatment of Castration Sensitive Prostate Cancer

Inclusion Criteria:

• All patients must have a histologically or cytologically proven diagnosis ofadenocarcinoma of the prostate. (Note: Gleason score not required if biopsy ofmetastasis was used to make the histologic diagnosis)

• All patients must have metastatic disease: either soft tissue and/or bony metastasesprior to initiation of androgen. Measurable disease is not required

• Baseline imaging must have been performed within 42 days before or 14 days afterinitiating luteinizing hormone releasing hormones (LHRH) therapy. All disease mustbe assessed and documented on the Baseline Tumor Assessment Form

• Patients may have started on LHRH therapy for metastatic prostate cancer providedthis was initiated no longer than 60 days prior to registration

• Patients may have received neoadjuvant and/or adjuvant LHRH therapy duringdefinitive treatment or salvage radiation; if so at least 12 months must haveelapsed from the last LHRH injection and baseline testosterone must be > 150ng/dL

• No restriction on bicalutamide used for flare prevention or combined therapyhowever bicalutamide must be stopped at registration

• Patients must have a Karnofsky performance status of 60 - 100

• Men of reproductive potential and those who are surgically sterilized (i.e.,vasectomy) must agree to practice effective barrier contraception or agree toabstain from intercourse while receiving treatment on this study and for at least 4months after protocol treatment ends

• Bilirubin =< 2 x institutional upper limit of normal (ULN) (obtained within 28 daysprior to registration)

• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x institutional ULN, or =< 5 x institutional ULN if liver metastases are present (obtained within 28 days prior to registration)

• Calculated creatinine clearance >= 30 mL/min using a serum creatinine obtainedwithin 28 days prior to registration

• Leukocytes >= 3,000/mcL (obtained within 28 days prior to registration)

• Absolute neutrophil count (ANC) >= 1,500/mcL (obtained within 28 days prior toregistration)

• Hemoglobin >= 9 g/dL (obtained within 28 days prior to registration)

• Platelets >= 100,000/mcL (obtained within 28 days prior to registration)

• All subjects must have the ability to understand and the willingness to sign awritten informed consent

• Patients may have received prior androgen deprivation therapy (ADT) -neoadjuvantand/or adjuvant, or in conjunction with salvage radiation - but it must not havelasted for more than 36 months. Single or combination therapy allowed. At least 6months must have elapsed since completion of androgen deprivation therapy in theneoadjuvant and/or adjuvant setting, and serum testosterone must be > 150 ng/mLwithin 28 days prior to registration. Note: Serum testosterone assessment isrequired for eligibility for only those with prior treatment with ADT

• Patients who have already started on LHRH therapy are eligible, provided nomore than 60 days have elapsed from LHRH injection (or surgical castration) formetastatic prostate cancer prior to registration. The start date of medicalcastration is considered the day the patient first received an injection of aLHRH agonist/antagonist (or orchiectomy), not an oral antiandrogen. Subjectsmay not already be taking abiraterone, enzalutamide, apalutamide or otherintensification agent during this time - bicalutamide is permitted

• Patients may have received palliative radiotherapy for symptomatic bone or visceralmetastasis, provided they have recovered from all side effects at the time ofregistration

• Patients may have received prior surgery. For all major surgeries, at least 14daysmust have elapsed since completion and patient must have recovered from all majorside effects of surgery per investigator's assessment

• Patients may have received or plan to receive concurrent bone targeting agents thatdo not have an effect on prostate specific antigen (PSA) (e.g. denosumab orbisphosphonate)

Exclusion Criteria:

• Patients must not have received prior and/or must not have any plans for receivingconcomitant therapy with ketoconazole, aminoglutethimide, or enzalutamide (MDV3100).Concurrent megestrol for hot flashes is allowed

• Patients must not have received any prior cytotoxic chemotherapy for metastaticprostate cancer

• Prior cytotoxic chemotherapy with curative intent in the neoadjuvant oradjuvant setting may be allowed at the discretion of the principalinvestigator. At least 2 years must have elapsed since completion of cytotoxicchemotherapy in the neoadjuvant and/or adjuvant setting

• Patients with known brain metastases are not eligible. Brain imaging studies are notrequired for eligibility if the patient has no neurologic signs or symptomssuggestive of brain metastasis. But, if brain imaging studies are performed, theymust be negative for disease

• Patients must not have New York Heart Association class III or IV heart failure atthe time of screening. Patients must not have any thromboembolic event, unstableangina pectoris, myocardial infarction, or serious uncontrolled cardiac arrhythmiawithin 6 months prior to registration

• Patients must not have uncontrolled hypertension (defined as blood pressure > 160mmHg systolic and > 90 mmHg diastolic at 2 separate measurements no more than 60minutes apart) despite appropriate medical therapy. Note: Patients may be rescreenedafter adjustments of antihypertensive medications

• Patients must not be known to have human immunodeficiency virus (HIV) infection,active chronic hepatitis B or C, life-threatening illness unrelated to cancer, orany serious medical or psychiatric illness that could, in the investigator'sopinion, potentially interfere with participation in this study

• Patients with a known history of primary and secondary adrenal insufficiency are noteligible

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to any of the study drugs

• Patients may not be receiving any other investigational agents, or concurrentbiological, chemotherapy, or radiation therapy. Previous experimental therapy musthave been completed at least 28 days prior to registration

• Patients must not have known gastrointestinal (GI) disease or GI procedure thatcould interfere with the GI absorption or tolerance of any of the study drugs,including difficulty swallowing oral medications

• No other prior malignancy is allowed except for the following: adequately treatedbasal cell or squamous cell skin cancer, adequately treated stage I or II cancerfrom which the patient is currently in complete remission, or any other cancer fromwhich the patient has been disease-free for 5 years