Calcitriol, Ketoconazole, and Dexamethasone in Treating Patients With Metastatic or Unresectable Solid Tumors

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor

  • Metastatic or unresectable disease
• Standard curative or reliable palliative therapy is no longer effective OR does not exist
• Brain metastases allowed provided they have been treated with surgery or radiotherapy AND are stable

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Hemoglobin ≥ 8 g/dL
• Platelet count ≥ 75,000/mm^3

Hepatic

• AST/ALT ≤ 2.5 times upper limit of normal
• Bilirubin normal
• No unstable or uncompensated hepatic disease

Renal

• Creatinine ≤ 2 mg/dL
• No unstable or uncompensated renal disease
• No history of kidney, urethral, or bladder stones within the past 5 years

Cardiovascular

• Ejection fraction ≥ 30%
• No symptomatic congestive heart failure
• No significant arrhythmias
• No myocardial infarction within the past 3 months
• No unstable angina pectoris
• No unstable or uncompensated cardiac disease
• No other significant heart disease

Pulmonary

• No unstable or uncompensated respiratory disease

Immunologic

• No known severe hypersensitivity to ketoconazole or calcitriol or any of the excipients of these products
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to the study drugs
• No ongoing or active infection

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception prior to, during, and for 3 months after completion of study treatment
• Able to receive oral medication
• No sperm donation during and for ≥ 3 months after completion of study treatment
• No evidence of significant clinical disorder or laboratory finding that would preclude study participation
• No other severe or uncontrolled systemic disease
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent prophylactic growth factors, including filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

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

  • Any number of prior chemotherapy regimens allowed

Endocrine therapy

• No concurrent systemic glucocorticoid therapy > physiologic replacement doses

Radiotherapy

• See Disease Characteristics
• Any number of prior radiotherapy regimens allowed

Surgery

• See Disease Characteristics
• Recovered from prior major surgery
• Concurrent surgery allowed provided ≥ 7 days has passed since the last dose of ketoconazole (ketoconazole may be restarted after adequate wound healing)

Other

• Recovered from prior anticancer therapy

  • Alopecia allowed
• More than 30 days since prior nonapproved or investigational agents
• More than 7 days since prior and no concurrent thiazides
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent digoxin or calcium supplementation
• No concurrent proton pump inhibitor or H2 blockers

• No concurrent medications that would alter the levels of ketoconazole and/or calcitriol, including the following:

  • Phenytoin
  • Carbamazepine
  • Barbiturates (e.g., phenobarbital)
  • Rifampin
  • Hypericum perforatum (St. John's wort)
• No concurrent drugs that would be significantly impaired in a clinically important way by ketoconazole
• No other concurrent investigational or commercial agents or therapies for this malignancy