Interleukin-2 and Bryostatin 1 in Treating Patients With Advanced Kidney Cancer

PRIMARY OBJECTIVES:

I. Determine the objective response rate in patients with advanced renal cell carcinoma treated with interleukin-2 (IL-2) and bryostatin 1.

II. Compare the toxicity of 3 different doses of bryostatin 1 given in combination with a fixed dose of IL-2 in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of three dose levels of bryostatin 1.

ARM I: Patients receive interleukin-2 (IL-2) subcutaneously on days 1-4, 8-11, and 15-18. For the second and subsequent courses of IL-2, patients also receive lowest dose bryostatin 1 IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive IL-2 as in arm I and middle dose bryostatin 1 IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive IL-2 as in arm I and highest dose bryostatin 1 IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity.

Patients with stable or responding disease may receive 3 additional courses of therapy. An additional cohort of patients receives treatment as above at a higher dose to evaluate toxicity.

Patients are followed for 1 year.

PROJECTED ACCRUAL: A total of 24-65 patients (8-16 per bryostatin 1 dose level) will be accrued for this study within 14-27 months.

Inclusion criteria

• Histologically or cytologically confirmed renal cell carcinoma

• Recurrent or refractory advanced disease
• Newly diagnosed disease with no appropriate standard therapy available
• Measurable disease
• No active CNS metastases

• Single prior CNS metastasis allowed if all of the following are true:

• Previously resected and irradiated
• No evidence of progressive CNS disease for at least 8 weeks after completion of therapy
• No requirement for steroids or anti-seizure medications
• Performance status - ECOG 0-2
• More than 3 months
• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN
• Creatinine no greater than 2.0 mg/dL
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for at least 2 weeks after study for female patients and for 3 months after study for male patients
• No concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study entry
• No prior interleukin-2
• See Disease Characteristics
• See Disease Characteristics
• Prior radiotherapy to less than 50% of bone marrow allowed
• At least 4 weeks since prior radiotherapy
• See Disease Characteristics
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients