Enzalutamide and Niraparib in the Treatment of Metastatic Castrate-Resistant Prostate Cancer (CRPC)

Inclusion Criteria:

* Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
* Age ≥ 18 years at the time of consent.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 14 days prior to registration.
* Men who are not surgically sterile (vasectomy) must agree to use an acceptable method of contraception. Male subjects with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms from the first dose of study drug through at least 120 days after the last dose of study drug. Total abstinence for the same study period is an acceptable alternative.
* Documented histologically or cytologically confirmed adenocarcinoma of the prostate.
* Ongoing androgen deprivation therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or bilateral orchiectomy. Subjects who have not undergone orchiectomy must plan to continue GnRH analogue therapy for the duration of the trial.
* All subjects on oral anti-androgen therapy must have been off therapy for at least 4 weeks prior to registration (6 weeks for bicalutamide) to exclude an anti-androgen withdrawal response. Patients who received secondary anti-androgen therapy and did not exhibit a \>50% PSA decline, or subjects with any rise in PSA, objective or symptomatic progression following anti-androgen withdrawal will not be required to meet this withdrawal requirement.
* Documented metastatic disease with prostate-specific antigen (PSA) progression, radiographic progression, or both, despite receiving luteinizing hormone releasing hormone (LHRH) analogue therapy or orchiectomy with a serum testosterone level of 50 ng/dL or less.

  * PSA progression is defined as three successive rising PSA values with an interval of at least one week between determinations.
  * Radiographic progression is defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria or at least two new lesions on bone scan.
* At screening the serum testosterone must be 50 ng/dL or less and the PSA must be greater or equal to 2 ng/mL.
* Estimated life expectancy \> 6 months
* Prior treatment of CRPC, including docetaxel, cabazitaxel, sipuleucel-T, or Radium-223 is allowed.
* Prior therapy with abiraterone allowed for a maximum of 9 subjects.
* Prior chemotherapy must be completed at least 28 days prior to registration and the participant subject must have recovered from the acute toxic effects.

Exclusion Criteria:

* Prior enzalutamide or other next-generation androgen receptor- (AR) targeting therapy.
* Prior PARP-inhibitor therapy.
* History of or active central nervous system (CNS) metastases. Subjects with neurological symptoms must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis.
* Radioisotope or external beam radiation exposure in the last 4 weeks. Exposure to strontium, regardless of when exposure occurred.
* Prior radiation to 25% or more of the bone marrow.
* Treatment with any investigational agent within 28 days prior to registration.
* Known significant immunodeficiency as determined by the site investigator.
* Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, or other cancer for which the subject has been disease-free or stable for at least one year.
* Prolonged QTc over 470 ms.
* History of seizure.
* Clinically significant active infections on systemic therapy as judged by the site investigator.