OBJECTIVES:

• Determine the maximum tolerated dose of CCI-779 in combination with interferon alfa in patients with locally advanced or metastatic renal cell cancer.
• Determine the safety and tolerability of this regimen in these patients.
• Determine, preliminarily, any antitumor activity of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive interferon alfa (IFN-A) subcutaneously 3 times a week. Beginning on week 2, patients also receive CCI-779 IV over 30 minutes once weekly. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of at least 6 patients receive escalating doses of CCI-779 and then IFN-A until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 20 additional patients are treated at that dose level.

Patients are followed at 30 days.

PROJECTED ACCRUAL: Approximately 50 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed locally advanced or metastatic renal cell cancer

  • Progressive disease after treatment with 0-2 courses of immunotherapy, chemotherapy, or other systemic therapy for advanced disease
• Measurable or evaluable disease

• No concurrent CNS metastases

  • Prior CNS metastases allowed if no residual disease by MRI

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST and ALT no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases present)

Renal

• Creatinine less than 2 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No unstable angina
• No myocardial infarction within the past 6 months

Other

• Cholesterol no greater than 350 mg/dL
• Triglycerides no greater than 400 mg/dL
• HIV negative
• Not immunocompromised
• No active autoimmune disorder
• No active infection requiring antibiotic therapy
• No other serious concurrent illness
• No known hypersensitivity to components of CCI-779, interferon alfa, diphenhydramine hydrochloride, or both acetaminophen and nonsteroidal anti- inflammatory drugs
• No other major illness that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• At least 3 weeks since prior immunotherapy
• No prior interferon alfa
• No other concurrent immunotherapy
• No prophylactic growth factors
• Concurrent epoetin alfa allowed

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy
• No prior CCI-779
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy for malignancy (megestrol for appetite loss allowed)
• Concurrent inhaled or replacement steroids allowed

Radiotherapy

• At least 3 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• At least 3 weeks since prior surgery

Other

• See Disease Characteristics
• At least 3 weeks since prior immunosuppressive agents
• At least 4 weeks since prior investigational agents
• No other concurrent investigational agents
• No concurrent immunosuppressive therapy
• No concurrent anticonvulsants known to be cytochrome P450 inducers, ketoconazole, diltiazem, rifampin, terfenadine, cisapride, astemizole, or pimozide
• No concurrent maintenance therapy for life-threatening ventricular arrhythmia