OBJECTIVES:

• Determine the maximum tolerated dose of low-dose interleukin-2 administered with interleukin-12 in patients with advanced solid malignancies.
• Determine the toxicity of this regimen in these patients.
• Determine the anti-tumor effects of this regimen in these patients.
• Determine the impact of interleukin-2 on the magnitude and duration of in vivo immune activation induced by interleukin-12 in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive interleukin-12 (IL-12) IV on days 1 and 4 for 6 weeks. Beginning on day 4 of the third week, patients receive interleukin-2 (IL-2) subcutaneously 1 hour before and 20 hours after each dose of IL-12. On subsequent courses, IL-2 and IL-12 are administered on days 1 and 4 of each week. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients with disease response may continue treatment until complete response or disease progression.

Cohorts of 3-6 patients receive escalating doses of IL-12 and IL-2 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 3 weeks.

PROJECTED ACCRUAL: A total of 20-25 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic or unresectable solid tumor that is unlikely to respond to existing therapy or for which no curative therapy exists
• Measurable or evaluable disease which is clearly progressive
• No hematologic malignancies
• No brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1
• Karnofsky 80-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• WBC greater than 4,000/mm3
• Absolute neutrophil count greater than 1,500/mm3
• Platelet count greater than 100,000/mm3

Hepatic:

• Bilirubin less than 1.5 mg/dL
• SGOT and SGPT less than 2 times normal
• No active (clinical or subclinical) hepatitis B or C infection

Renal:

• Creatinine less than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No congestive heart failure
• No symptoms of coronary artery disease
• No serious cardiac arrhythmias
• No evidence of prior myocardial infarction

Other:

• No active infection requiring antibiotic therapy
• No medical condition requiring the use of corticosteroids during study
• No autoimmune or rheumatologic disease
• No seizure disorders
• No significant medical disease that would preclude study
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy and recovered
• At least 6 months since prior interleukin-2
• At least 12 months since prior interleukin-12
• No more than 2 prior biological response modifier treatment regimens

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for prior nitrosoureas or mitomycin) and recovered
• No more than 2 prior chemotherapy regimens
• No concurrent chemotherapy

Endocrine therapy:

• At least 4 weeks since prior hormonal therapy and recovered
• No concurrent hormonal therapy (including steroids and hormone replacement therapy)

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• No prior organ allografts

Other:

• At least 2 weeks since prior IV antibiotics
• No other concurrent investigational agents