Randomized Salvage Radiation Therapy Plus Enzalutamide Post Prostatectomy

Inclusion Criteria:

* Willing and able to provide written informed consent and Health Insurance Portability and Accountability Act (HIPPA) authorization for the release of personal health information.
* Males aged 18 years of age and above
* Patients must have adenocarcinoma of the prostate gland
* Patients must have received primary treatment with radical prostatectomy.
* Patients must have evidence of biochemical (PSA) relapse after prostatectomy
* Patients must have PSA within study range
* Patients must have non-metastatic (M0) disease, as defined by a lack of metastases seen on CT scan of the chest/abdomen/pelvis and whole-body radionuclide 99Technetium (Tc) bone scan, (or sodium fluoride PET scan) taken within 3 months of study entry.
* Patients must have had node negative (pN0) disease found at the time of surgery.
* Patients must have non-castrate levels of serum testosterone levels within study range.
* Patients must not have previously received hormonal therapy (LHRH agonist, antiandrogen, or both), with the exception of neoadjuvant or adjuvant hormones given in conjunction with prostatectomy.
* Patients must have Eastern Cooperative Oncology Group (ECOG)performance status of 0-1, and life expectancy greater 3 years.
* Patients must have laboratory test results within the certain ranges
* Patients must be disease-free from prior malignancies for greater than 3 years, with the exception of non-melanoma skin cancers and superficial urothelial cancers.
* Patients must have the ability to swallow the study drug whole as a tablet or capsule.
* Throughout study, male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration or per local guidelines where these require additional description of contraceptive methods.
* Throughout the study, patients must use a condom if having sex with a pregnant woman.

Exclusion Criteria:

* Currently active second malignancy
* Primary treatment with radiation therapy.
* Radiographic or clinical evidence of local-regional tumor recurrence,
* Concurrent use of other antiandrogens, estrogen-like agents, or 5a-reductase inhibitors.
* Use of systemic corticosteroids equivalent to prednisone (inhaled corticosteroids are permitted).
* Concurrent use of other anti-cancer agents or treatments.
* Serious concurrent medical illnesses (including uncontrolled major cardiac, pulmonary, Child-Pugh C liver or psychiatric diseases) or active major infections (including HIV, Hepatitis A-C).
* Clinically significant cardiovascular disease including:

  * Myocardial infarction within 6 months of Screening visit.
  * Uncontrolled angina within 3 months of Screening visit.
  * Congestive heart failure (within certain ranges)
  * History of clinically significant ventricular arrhythmias
  * Prolonged corrected QT interval
  * History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
  * Hypotension within certain ranges
  * Uncontrolled hypertension within certain ranges
* Medications which lowers seizure threshold.
* History of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism. Also, history of loss of consciousness or transient ischemic attack within 12months of enrollment (Day 1 visit).
* Patients taking medications that may have adverse interactions with enzalutamide