Hormone Therapy, Radiation Therapy, and Steroid 17alpha-monooxygenase TAK-700 in Treating Patients With High-Risk Prostate Cancer

Inclusion Criteria:

1. Histologically confirmed diagnosis of adenocarcinoma of the prostate within 180 daysprior to registration at high risk for recurrence as determined by one of thefollowing 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

2. History/physical examination within 60 days prior to registration.

3. Clinically negative lymph nodes as established by imaging [abdominal and/or pelviccomputerized 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 thenodes are < 2.0 cm.

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

•Equivocal bone scan findings are allowed if plain films are negative formetastasis.

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

6. 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 thepatient has started ADT he will not be eligible to participate in the quality oflife component of this study.

7. Prior testosterone administration is allowed if last administered at least 90 daysprior to registration.

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

9. Age ≥ 18

10. Complete blood count (CBC)/differential obtained within 14 days prior toregistration 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 toachieve Hgb ≥ 8.0 g/dl is acceptable.)

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

12. Bilirubin < 1.5x upper limit of normal (ULN) and alanine aminotransferase (ALT) oraspartate aminotransferase (AST) < 2.5x ULN within 21 days prior to registration

13. Serum testosterone within 21 days prior to registration

14. Chemistry (including sodium, potassium, chloride, bicarbonate (carbon dioxide),blood urea nitrogen (BUN), glucose, calcium, magnesium and phosphorous) and liverpanels (including albumin and alkaline phosphatase) obtained within 21 days prior toregistration

15. Fasting glucose, fasting insulin, lipid panel [cholesterol, triglyceride,high-density lipoprotein (HDL), low-density lipoprotein (LDL)], and Hemoglobin A1Cwithin 21 days prior to registration

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

17. Baseline electrocardiogram (ECG) within 180 days prior to registration

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

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

20. Agree to completely abstain from intercourse.

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

Exclusion Criteria:

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 bilateralorchiectomy for any reason.

5. Prior invasive malignancy (except non-melanoma skin cancer) unless disease-free ornot requiring systemic therapy for a minimum of 3 years.

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

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

•Any patient undergoing brachytherapy must have transrectal ultrasound confirmationof prostate volume <60 cc, American Urological Association (AUA) score ≤15 within 60days of registration, and no history of prior transurethral resection of theprostate (TURP); prior TURP is permitted for patients who receive external beamradiation 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 ofHealth and Human Services, National Institutes of Health National Cancer Institute, 2009), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, orsymptomatic cerebrovascular events), or any other cardiac condition (e.g.,pericardial effusion restrictive cardiomyopathy) within 6 months prior toregistration. Chronic stable atrial fibrillation on stable anticoagulant therapy isallowed.

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

13. ECG abnormalities of:

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

15. QTc interval > 460 msec

16. Patients who are sexually active and not willing/able to use medically acceptableforms of contraception; this exclusion is necessary because the treatment involvedin this study may be significantly teratogenic.

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

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

19. 10-day period following prostate biopsy;

20. following initiation of hormonal therapy.

21. Cushing's syndrome

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

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

24. Chronic treatment with glucocorticoids within one year

25. Uncontrolled hypertension despite appropriate medical therapy within 21 days priorto registration (blood pressure of greater than 150 mm Hg systolic and 90 mm Hgdiastolic at 2 separate measurements no more than 60 minutes apart during Screeningvisit)

26. Unwilling or unable to comply with the protocol or cooperate fully with theinvestigator and site personnel.

27. Major surgery within 14 days prior to registration

28. Serious infection within 14 days prior to registration

29. Uncontrolled nausea, vomiting, or diarrhea [Common Terminology Criteria for AdverseEvents (CTCAE) grade ≥ 3] despite appropriate medical therapy at the time ofregistration

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