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
  • Coumadin
  • 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