DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the prostate (minimum of 6 biopsies
required) meeting 1 of the following criteria:
- Clinical stage T1c or T2 with high-grade disease (Gleason score 8-10) on initial
biopsy and PSA > 10 ng/mL
- Clinical stage T2b-T2c with Gleason grade >= 7
- No metastatic disease
- No histological variants (other than adenocarcinoma) in the primary tumor
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2 (Karnofsky 60-100%)
- Leukocytes >= 3,000/mm^3
- ANC >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Total bilirubin normal
- AST and/or ALT <= 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance >= 50 mL/min
- PT, PTT, and fibrinogen normal and no history of substantial non-iatrogenic bleeding
diathesis
- Must be a candidate for radical prostatectomy
- No major co-morbidity as determined by the treating physician
- Fertile patients must use 2 methods of effective contraception during and for >= 12
months after completion of study therapy
- Able to swallow capsules
- No co-existing medical diseases including, but not limited to, any of the following:
- Unstable angina
- Cardiac arrhythmia
- Myocardial infarction within the past 6 months
- Ongoing maintenance therapy for life-threatening ventricular arrhythmia
- Symptomatic congestive heart failure
- Uncontrolled hypertension
- Ongoing or active infection
- Psychiatric illness and/or social situations that would limit compliance with
study requirements
- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to Hedgehog antagonist GDC-0449 or luteinizing hormone-releasing
hormone analogues
- No malabsorption syndrome or other condition that would interfere with intestinal
absorption
- No clinically important (in the opinion of the treating physician) history of liver
disease, including viral or other hepatitis or cirrhosis
- No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia defined as
< the lower limit of normal for the institution, despite adequate electrolyte
supplementation
- Prior malignancy allowed provided < 30% chance of relapse within the next 5 years in
the opinion of the treating physician
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since prior antiandrogen treatment
- No prior chemotherapy or radiotherapy for prostate cancer
- No prior Hedgehog antagonist GDC-0449
- No prior or concurrent androgen ablation of > 4 weeks duration
- No prior systemic treatment for cancer within the past 6 months
- No other concurrent investigational agents
- No concurrent medications with narrow therapeutic indices that are metabolized by
cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)
- No concurrent antiretroviral therapy for HIV-positive patients
- No concurrent therapy with the following drugs:
- 5?-reductase inhibitors (e.g., finasteride, dutasteride)
- Megestrol acetate
- Cyproterone acetate
- Androgen-receptor partial agonists
- Ketoconazole
- Chemotherapy (e.g., docetaxel, mitoxantrone, vinorelbine)
- Immunotherapy (e.g., cancer vaccine, GM-CSF)
- Estrogens (e.g., diethylstilbestrol)
