Enzalutamide + External Beam Rt For Prostate

- The participant will be given a study drug-dosing diary for each of 6 treatment cycles.
Each treatment cycle lasts 28 days (4 weeks), during which time the participant will be
taking the study drug enzalutamide by mouth (4 pills daily). The diary will also include
special instructions for taking the enzalutamide.

- The participant will also be undergoing external beam radiation therapy during the
study, for a duration of 8 ½-10 weeks. Treatment will be administered on an outpatient
basis. This part of the study is considered standard of care.

- The participant will be required to have fiducial markers placed within the prostate as
part of this study. These are very small gold markers that are placed in the prostate.
This procedure is similar to the biopsy that the participant had to diagnose their
cancer. This procedure is routinely performed to permit imaging and position corrections
to improve the precision of the external beam (radiation) delivery (Image Guided
Radiation Therapy). The placement of the three gold markers is performed by an
Urologist. The fiducials are placed under ultrasound guidance. This is also considered
standard of care and is not experimental.

- Planned Follow-up: Participants will be followed on study at a 3 month follow-up after
treatment (cessation of enzalutamide). Additional follow-up to assess the status of the
participant's cancer will be conducted at the discretion of the treating physicians as
part of the participant's routine medical care.

Inclusion Criteria:

- Study population: Participants must have histologically confirmed malignancy and are
candidates for external beam radiation therapy. Patients eligible for this study must
have intermediate risk disease defined as PSA values between 10-20 ng/ml and/or T2b-c
and/or Gleason grade 7. If all three are present, less than 50% of the core biopsies
can be positive.

- Patients previously diagnosed with low risk (Gleason score < 6, clinical stage < T2a,
and PSA< 10) prostate cancer undergoing active surveillance who are re-biopsied and
found to have intermediate risk disease according to the protocol criteria are
eligible for enrollment within 180 days of the repeat biopsy procedure.

- Age 18 years or more.

- Life expectancy of greater than 1 year.

- ECOG performance status ≤ 2 (see Appendix D).

- Participants must have normal organ and marrow function as defined below:

- Leukocytes ≥3,000/mcL

- Platelets ≥80,000/mcL

- Total bilirubin < 2X institutional upper limit

- AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal

- Creatinine < 2x institutional limits .

- The effects of enzalutamide on the developing human fetus are unknown. For this reason
and because enzalutamide may be teratogenic, men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation.

Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

- Patients must NOT meet any of the following exclusion criteria

- Received an investigational agent within 4 weeks prior to enrollment

- Stage T4 prostate cancer by clinical examination or radiologic evaluation.

- Hypogonadism or severe androgen deficiency as defined by screening serum testosterone
less than 50 ng/dL below the normal range for the institution.

- Prior androgen deprivation, chemotherapy, surgery, or radiation for prostate cancer.

- Receiving concurrent androgens, anti-androgens, estrogens, or progestational agents,
or received any of these agents within the 6 months prior to enrollment or having
taken finasteride or dutasteride within 30 days of registration.

- History of another active malignancy within the previous 5 years other than curatively
treated nonmelanomatous skin cancer and superficial bladder cancer. Participants
treated for malignancy with no relapse within two years are eligible to participate in
the study.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection.

- Severe concurrent disease, infection, or co-morbidity that, in the judgment of the
Investigator, would make the patient inappropriate for enrollment.

- Unwilling to use contraceptives while on study if relevant to patient.

- History of seizure or any condition or concurrent medication that may predispose to
seizure.

- History of loss of consciousness or transient ischemic attack within 12 months prior
to enrollment.

- Clinically significant cardiovascular disease, including:

- Myocardial infarction within 3 months of enrollment;

- Uncontrolled angina within 3 months of enrollment;

- Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or
history of congestive heart failure NYHA class 3 or 4 in the past, unless a
screening echocardiogram or multi-gated acquisition scan performed within 3
months results in a left ventricular ejection fraction ≥ 45%;

- History of clinically significant ventricular arrhythmias (e.g., ventricular
tachycardia, ventricular fibrillation, torsades de pointes);

- History of Mobitz II second degree or third degree heart block without a
permanent pacemaker in place;

- Hypotension as indicated by systolic blood pressure < 86 mmHg on 2 consecutive
measurements at the Screening visit;

- Bradycardia as indicated by a heart rate < 50 beats per minute at the Screening
visit;

- Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or
diastolic blood pressure > 105 mmHg on 2 consecutive measurements at the
screening visit;

- EKG demonstrating equal to or greater than grade III toxicity according the NCI
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

- History of gastrointestinal disorders (medical disorders or extensive surgery)
that may interfere with the absorption of oral study drug(s) within 3 months of
enrollment.

- Major surgery within 4 weeks of registration.

- Previous use, or participation in a clinical trial, of an investigational agent
that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683,
TAK-448) or targets the androgen receptor (e.g., enzalutamide, BMS 641988);
ketoconazole.

- Any condition or reason that, in the opinion of the Investigator, interferes with
the ability of the patient to participate in the trial, places the patient at
undue risk, or complicates the interpretation of safety data.

- Need for any of the medications on the list of drugs to be used with caution or
to be avoided (see APPENDIX F).

- Use of herbal or alternative remedies that may affect hormonal status such as
Prostasol or PC-SPES.