Phase III Trial of Dose Escalated Radiation Therapy and Standard Androgen Deprivation Therapy (ADT) With a GNRH Agonist vs. Dose Escalated Radiation Therapy and Enhanced ADT With a GNRH Agonist and TAK-700 For Men With High Risk Prostate Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- 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 (risk group):

- 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

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

- Study entry PSA obtained during the following time frames:

- 10-day period following prostate biopsy

- Following initiation of hormonal therapy

- Clinically negative lymph nodes as established by imaging (abdominal and pelvic CT or
abdominal and pelvic 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

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

- No definite evidence of metastatic disease

- 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 radiotherapy
(EBRT) only

PATIENT CHARACTERISTICS:

- Height, weight, Zubrod performance status 0-1

- Absolute neutrophil count (ANC) ≥ 1,800 cells/mm^3

- Platelets ≥ 100,000 cells/mm^3

- Hemoglobin ≥ 8.0 g/dL (The use of transfusion or other intervention to achieve Hgb ≥
8.0 g/dL is acceptable)

- Serum creatinine < 2.0 mg/dL

- Creatinine clearance > 40 mL/minute

- Bilirubin < 1.5 x upper limit of normal (ULN)

- ALT or AST < 2.5 x ULN

- No PSA > 150 ng/mL

- Screening calculated ejection fraction ≥ ULN by multiple-gated acquisition (MUGA)
scan or by echocardiogram

- Patients, even if surgically sterilized (i.e., status post vasectomy), must 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

- No prior invasive malignancy (except non-melanoma skin cancer) unless disease-free or
not requiring systemic therapy for a minimum of 3 years

- No known hypersensitivity to TAK-700 or related compounds

- No history of adrenal insufficiency

- No history of myocardial infarction, unstable symptomatic ischemic heart disease,
ongoing arrhythmias of grade > 2 (NCI CTCAE, version 4.02) thromboembolic events
(e.g., 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

- No New York Heart Association Class III or IV heart failure

- No ECG abnormalities of Q-wave infarction, unless identified 6 or more months prior
to screening, or QTc interval > 460 msec

- No prior allergic reaction to the drugs involved in this protocol

- No Cushing syndrome

- No severe chronic renal disease or chronic liver disease

- No 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)

- No serious infection within 14 days prior to registration

- No uncontrolled nausea, vomiting, or diarrhea (CTCAE grade ≥ 3) despite appropriate
medical therapy at the time of registration

- No known gastrointestinal (GI) disease or GI procedure that could interfere with the
oral absorption or tolerance of TAK-700, including difficulty swallowing tablets

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

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

- No prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral
orchiectomy for any reason

- No prior systemic chemotherapy for prostate cancer

- Prior chemotherapy for a different cancer is allowed

- No prior radiotherapy, including brachytherapy, to the region of the prostate that
would result in overlap of radiation therapy fields

- No previous hormonal therapy, such as LHRH agonists (e.g., goserelin, leuprolide),
anti-androgens (e.g., flutamide, bicalutamide), estrogens (e.g., DES), or surgical
castration (orchiectomy)

- No chronic treatment with glucocorticoids within one year

- No major surgery within 14 days prior to registration

- No other investigational agent

- No other anticancer therapy

- No concurrent hormonal therapies including estrogens or herbal products

- No concurrent ketoconazole or aminoglutethimide

- No chronic use of systemic corticosteroids, such as oral prednisone