Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed androgen-independent adenocarcinoma of the
prostate

- Advanced or recurrent disease for which standard curative or reliable palliative
therapy does not exist or is no longer effective

- Measurable disease with elevated prostate-specific antigen (PSA) or evaluable disease
(PSA elevation will constitute evaluable disease)

- Patients who have received prior antiandrogens or progestational agents as therapy
for prostate cancer must discontinue therapy and demonstrate a rising PSA ≥ 28 days*
after discontinuation NOTE: *At least 42 days for bicalutamide or nilutamide

- Patients undergoing androgen deprivation using luteinizing hormone-releasing hormone
(LHRH) analogues must continue therapy or undergo orchiectomy to maintain castrate
levels of testosterone

- Patients with brain metastases which are stable and have been treated for surgery or
irradiation are eligible

PATIENT CHARACTERISTICS:

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 3 months

- Leukocytes ≥ 3,000/mm^3

- Hemoglobin ≥ 8 g/dL

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 75,000/mm^3

- Total bilirubin normal

- AST/ALT ≤ 2.5 x upper limit of normal

- Creatinine ≤ 2 mg/dL

- Calcium normal

- Must be able to receive oral medications, including oral capsules

- No known severe hypersensitivity to ketoconazole, calcitriol, or any of the
excipients of these products

- No history of allergic reaction attributed to compounds of similar chemical or
biologic composition to calcitriol, ketoconazole, or other agents used in the study

- No evidence of any other significant clinical disorder or laboratory finding that
would make it undesirable for the patient to participate in the trial

- No history of kidney, ureteral, or bladder stones within the past 5 years

- No incomplete healing from prior oncologic treatments or other major surgery

- No unresolved chronic toxicity > grade 2

- No heart failure or significant heart disease, including any of the following:

- Significant arrhythmias

- Myocardial infarction within the past 3 months

- Unstable angina pectoris

- Documented ejection fraction < 30%

- No other severe or uncontrolled systemic disease (e.g., unstable or compensated
respiratory, cardiac, hepatic, or renal disease) or intercurrent illness including,
but not limited to any of the following:

- Ongoing or active infection

- Symptomatic congestive heart failure

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

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from prior anticancer therapy

- At least 7 days since prior thiazide therapy

- At least 30 days since prior treatment with a non-approved or investigational drug or
agent

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)

- At least 4 weeks since prior radiotherapy or cytotoxic therapy

- No more than 2 prior cytotoxic chemotherapy regimens

- Retinoids, vitamin D analogues, PPARγ agonists or antagonists, antiandrogens,
progestational agents, estrogens, PC-SPES, LHRH analogues, vaccines, and
cytokines are not considered cytotoxics

- Prior ketoconazole and glycocorticoids allowed

- Concurrent megestrol acetate for hot flashes at a dose of ≤ 40 mg/day allowed

- No concurrent digoxin therapy

- No concurrent systemic glucocorticoid therapy at greater than physiologic replacement
doses

- No concurrent calcium supplementation

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent proton pump inhibitors or H2 blockers

- No concurrent use of any of the following:

- Phenytoin

- Carbamazepine

- Barbiturates

- Rifampicin

- Phenobarbital

- Hypericum perforatum (St. John wort)

- Alfentanil

- Alfuzosin

- Almotriptan

- Alprazolam

- Amiodarone

- Amitriptyline

- Aprepitant

- Amprenavir

- Aripiprazole

- Bepridil

- Bortezomib

- Bosentan

- Budesonide

- Buprenorphine

- Buspirone

- Cilostazol

- Cisapride

- Cyclosporine

- Delavirdine

- Didanosine

- Digoxin

- Disopyramide dofetilide

- Donepezil

- Eletriptan

- Eplerenone

- Fluticasone

- Fosamprenavir

- Galantamine

- Systemic griseofulvin

- Indinavir

- Levobupivacaine

- Lopinavir

- Midazolam

- Mifepristone

- Modafinil

- Nateglinide

- Nefazodone

- Nelfinavir

- Oxcarbazepine

- Pimozide

- Quetiapine

- Quinidine

- Repaglinide

- Rifabutin

- Rifampin

- Rifapentine

- Ritonavir

- Saquinavir

- Valdecoxib

- Vardenafil

- Ziprasidone

- Statins

- Calcium channel blockers

- Macrolides

- Sildenafil

- Sirolimus

- Tacrolimus

- Tadalafil

- Tolterodine

- Theophyllines

- Triazolam

- Zonisamide

- Other agents that would be significantly perturbed in a clinically important way
by the P450 inhibitory properties of ketoconazole