Histologically confirmed diagnosis of adenocarcinoma of the prostate within 180 days prior to registration at high risk for recurrence as determined by one of the following combinations:

Gleason Score (GS) = 9, PSA = 150 ng/mL, any T stage

GS = 8, PSA \< 20 ng/mL, T stage = T2

GS = 8, PSA = 20-150 ng/mL, any T stage

GS = 7, PSA = 20-150 ng/mL, any T stage

History/physical examination within 60 days prior to registration.

Clinically negative lymph nodes as established by imaging \[abdominal and/or pelvic computerized tomography (CT) or abdominal and/or pelvic magnetic resonance imaging (MRI)\], nodal sampling, or dissection within 90 days prior to registration.

Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are \< 2.0 cm.

No distant metastases (M0) on bone scan within 90 days prior to registration (18F-Na bone scan is an acceptable substitute).

Equivocal bone scan findings are allowed if plain films are negative for metastasis.

Baseline serum prostate-specific antigen (PSA) value performed with an FDA-approved assay (e.g., Abbott, Hybritech), obtained prior to any luteinizing hormone-releasing hormone (LHRH) or anti-androgen therapy, within 180 days of randomization.

Androgen deprivation therapy (ADT), such as LHRH agonists (e.g., goserelin, leuprolide), anti-androgens (e.g., flutamide, bicalutamide), estrogens (e.g., DES), or surgical castration (orchiectomy), may have been started prior to registration, provided that registration is within 50 days of beginning ADT. Please note: If the patient has started ADT he will not be eligible to participate in the quality of life component of this study.

Prior testosterone administration is allowed if last administered at least 90 days prior to registration.

Zubrod Performance Status 0-1 within 21 days prior to registration

Age = 18

Complete blood count (CBC)/differential obtained within 14 days prior to registration on study, with adequate bone marrow function defined as follows:

Absolute neutrophil count (ANC) = 1,800 cells/mm3

Platelets = 100,000 cells/mm3

Hemoglobin = 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb = 8.0 g/dl is acceptable.)

Serum creatinine \< 2.0 mg/dl and creatinine clearance (can be calculated) \> 40 mL/minute within 21 days prior to registration

Bilirubin \< 1.5x upper limit of normal (ULN) and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 2.5x ULN within 21 days prior to registration

Serum testosterone within 21 days prior to registration

Chemistry (including sodium, potassium, chloride, bicarbonate (carbon dioxide), blood urea nitrogen (BUN), glucose, calcium, magnesium and phosphorous) and liver panels (including albumin and alkaline phosphatase) obtained within 21 days prior to registration

Fasting glucose, fasting insulin, lipid panel \[cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL)\], and Hemoglobin A1C within 21 days prior to registration

Screening calculated ejection fraction of = to institutional lower limit of normal by multiple gated acquisition (MUGA) scan or by echocardiogram (ECHO).

Baseline electrocardiogram (ECG) within 180 days prior to registration

Patients, even if surgically sterilized (ie, status post vasectomy), who:

Agree to practice effective barrier contraception during the entire study treatment period and for 4 months (120 days) after the last dose of study drug, or

Agree to completely abstain from intercourse.

Patient must be able to provide study-specific informed consent prior to study entry.

1. PSA \> 150

2. Definite evidence of metastatic disease.

3. Pathologically positive lymph nodes or nodes \> 2.0 cm on imaging.

4. Prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy for any reason.

5. Prior invasive malignancy (except non-melanoma skin cancer) unless disease-free or not requiring systemic therapy for a minimum of 3 years.

6. Prior systemic chemotherapy for prostate cancer (Note that prior chemotherapy for a different cancer is allowed).

7. Prior radiotherapy, including brachytherapy, to the region of the prostate that would result in overlap of radiation therapy fields.

Any patient undergoing brachytherapy must have transrectal ultrasound confirmation of prostate volume \<60 cc, American Urological Association (AUA) score =15 within 60 days of registration, and no history of prior transurethral resection of the prostate (TURP); prior TURP is permitted for patients who receive external beam radiation therapy \[EBRT\] only).

8. Previous hormonal therapy for \> 50 days.

9. Known hypersensitivity to TAK-700 or related compounds

10. A history of adrenal insufficiency

11. History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade \> 2 \[NCI CTCAE, version 4.02\] (U.S. Department of Health and Human Services, National Institutes of Health National Cancer Institute, 2009), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (e.g., pericardial effusion restrictive cardiomyopathy) within 6 months prior to registration. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.

12. New York Heart Association Class III or IV heart failure.

13. ECG abnormalities of:

1. Q-wave infarction, unless identified 6 or more months prior to screening

2. QTc interval \> 460 msec

14. Patients who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

15. Prior allergic reaction to the drugs involved in this protocol.

16. Study entry PSA obtained during the following time frames:

1. 10-day period following prostate biopsy;

2. following initiation of hormonal therapy.

17. Cushing's syndrome

18. Severe chronic renal disease (serum creatinine \> 2.0 mg/dl and confirmed by creatinine clearance \< 40 mL/minute)

19. Chronic liver disease (bilirubin \> 1.5x ULN, ALT or AST \> 2.5x ULN)

20. Chronic treatment with glucocorticoids within one year

21. Uncontrolled hypertension despite appropriate medical therapy within 21 days prior to registration (blood pressure of greater than 150 mm Hg systolic and 90 mm Hg diastolic at 2 separate measurements no more than 60 minutes apart during Screening visit)

22. Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel.

23. Major surgery within 14 days prior to registration

24. Serious infection within 14 days prior to registration

25. Uncontrolled nausea, vomiting, or diarrhea \[Common Terminology Criteria for Adverse Events (CTCAE) grade = 3\] despite appropriate medical therapy at the time of registration

26. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-700, including difficulty swallowing tablets

• adenocarcinoma of the prostate

• Androgen Antagonists

• Antineoplastic Agents

• Antineoplastic Agents, Hormonal

• Bicalutamide

• Buserelin

• Contraceptive Agents

• Contraceptive Agents, Female

• Deslorelin

• Enzyme Inhibitors

• Fertility Agents

• Fertility Agents, Female

• Flutamide

• Genital Diseases, Male

• Genital Neoplasms, Male

• Goserelin

• Hormone Antagonists

• Hormones, Hormone Substitutes, and Hormone Antagonists

• Leuprolide

• Luteolytic Agents

• Molecular Mechanisms of Pharmacological Action

• Neoplasms

• Neoplasms by Site

• Pharmacologic Actions

• Physiological Effects of Drugs

• Prostatic Diseases

• Prostatic Neoplasms

• Reproductive Control Agents

• RTOG 1115

• stage I prostate cancer

• stage IIA prostate cancer

• stage IIB prostate cancer

• stage III prostate cancer

• stage IV prostate cancer

• Therapeutic Uses

• Triptorelin

• Urogenital Neoplasms

• Oncology (Adult)

• National Cancer Institute (NCI)

• NRG Oncology

• Radiation Therapy Oncology Group