Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed prostate cancer

- Hormone-sensitive disease, as evidenced by a serum total testosterone level >
150 ng/dL

- No evidence of metastatic disease on physical exam, CT abdomen/pelvis (or MRI),
chest x-ray or CT scan and bone scan within 6 weeks prior to randomization

- Underwent prior definitive surgery or radiotherapy

- Must have evidence of biochemical failure after primary therapy and subsequent
progression as determined by 1 of the following:

- Prostate-specific antigen (PSA) ≥ 0.4 ng/mL (in case of radical prostatectomy)

- PSA rise ≥ 2 ng/mL above the nadir PSA (in case of radiotherapy)

- Baseline PSA must be at least 2 ng/mL and no greater than 50 ng/mL

- PSA doubling time (PSADT) < 12 months

PATIENT CHARACTERISTICS:

- ECOG performance status 0 - 1

- Granulocytes ≥ 1,500/mm^3

- Platelet count ≥ 75,000/mm^3

- Serum creatinine normal or creatinine clearance ≥ 60 mL/min

- Serum total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 2.5 times ULN

- SGOT and SGPT < 2.5 times ULN

- PT/INR normal

- Fertile patients must use effective barrier contraception during and for at least 3
months after completion of study treatment

- No gastrointestinal (GI) tract disease resulting in: inability to take oral
medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical
procedures affecting absorption, or uncontrolled inflammatory GI disease (e.g.,
Crohn's, ulcerative colitis)

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to enzastaurin hydrochloride or bicalutamide

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness/social situations that would limit compliance with study
requirements

- A history of other malignancy is permitted if the patient is predicted to be
disease-free for 2 years

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- More than 4 weeks since prior salvage therapy with intent to cure (i.e., surgery,
radiotherapy, or other local ablative procedures)

- More than 4 weeks since prior prophylactic radiotherapy to prevent gynecomastia

- More than 1 year since prior therapy modulating testosterone levels (such as
luteinizing-hormone releasing-hormone agonists/antagonists and antiandrogens) unless
in the neoadjuvant or adjuvant setting

- No 5 alpha reductase inhibitors, ketoconazole, megestrol acetate, systemic steroids,
or herbal supplements during PSA value collection

- At least 14 days since prior enzyme-inducing anti-epileptic drugs (EIAEDs)

- Patients who must begin EIAED therapy while on study are allowed to remain

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent anticoagulant therapy

- Low dosage acetyl salicylic acid ≤ 325 mg/day allowed

- No other concurrent investigational agents or anticancer therapy (i.e., chemotherapy,
immunotherapy, radiotherapy, surgery for cancer, or experimental medications)

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to enzastaurin or bicalutamide

- Prior neoadjuvant and/or adjuvant therapy ≤ 4 weeks prior to randomization (i.e.,
hormones, chemotherapy, vaccines, or experimental agents) allowed if PSA rise and
PSADT were documented after testosterone level was > 150 ng/dL