Genistein and Interleukin-2 in Treating Patients With Metastatic Melanoma or Kidney Cancer

OBJECTIVES:

Primary

• Measure the differences in peak and duration of the expansion of circulating CD4-positive, CD8-positive, and CD4-, CD25-, and CD56-positive cells (dim and bright) at different time points during therapy with interleukin-2 (IL-2) alone and plus genistein in patients with metastatic malignant melanoma or renal clear cell carcinoma.

Secondary

• Evaluate the differences in peripheral blood mononuclear cell gene expression following high-dose IL-2 with and without genistein and compare to baseline.
• Determine the overall response rate (partial and complete) in patients treated with these regimens.
• Determine the safety and toxic effects of these regimens in these patients.
• Determine the time to progression in patients treated with these regimens.

OUTLINE: This is a pilot study.

Patients receive high-dose interleukin-2 IV over 15 minutes twice daily on days 1 and 15 and 3 times daily on days 2-5 and 16-19. Patients also receive oral genistein twice daily on days 10-19.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Documented histologically confirmed malignant melanoma or renal clear cell carcinoma

• Metastatic disease
• At least 1 measurable lesion that can be accurately measured in at least one dimension with longest diameter > 20 mm using conventional techniques OR > 10 mm with spiral CT scan

• If the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology
• Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules or palpable lymph nodes)
• The following are considered non-measurable lesions:

• Bone lesions
• Leptomeningeal disease
• Ascites
• Pleural/pericardial effusion
• Inflammatory breast disease
• Lymphangitis cutis/pulmonis
• Cystic lesions
• Abdominal masses that are not confirmed and followed by imaging techniques
• No CNS metastases by CT scan or MRI

PATIENT CHARACTERISTICS:

• ECOG performance status < 2
• Life expectancy ≥ 4 months
• Serum creatinine < 2.0 mg/dL OR creatinine clearance > 50 mL/min
• Bilirubin normal
• Platelets > 100,000/mm³
• WBC > 3,500/mm³
• No evidence of congestive heart failure
• No symptom of coronary artery disease
• No serious cardiac arrhythmias
• A pretreatment cardiac stress test must be performed within 42 days of IL-2 treatment if any cardiac symptoms present (patients with documented ischemia on the pretreatment cardiac stress test will be excluded from the study)
• Adequate pulmonary reserve

• FEV_1 > 75% of predicted
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Negative pregnancy test
• No known HIV-positive patients
• No evidence of active infection requiring antibiotic therapy
• No contraindication to treatment with pressor agents
• No significant medical disease which, in the opinion of the investigator, may interfere with completion of the study
• No history of another malignancy other than basal cell skin cancer within 5 years

PRIOR CONCURRENT THERAPY:

• Recovered from all toxic effects of prior therapy
• No radiotherapy, chemotherapy, or immunotherapy in the 4 weeks prior to the first dose of the study treatment
• No systemic corticosteroids in the 4 weeks prior to treatment
• No previous investigational agent within 4 weeks prior to the start of the study
• No prior interleukin-2 therapy
• No organ allografts allowed
• No concurrent radiotherapy, chemotherapy, or immunotherapy
• No concurrent corticosteroids
• No concurrent chronic medication for asthma