RATIONALE: Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of interleukin-12 and trastuzumab in treating patients who have cancer that has high levels of HER2/neu and has not responded to previous therapy.

OBJECTIVES: I. Determine the maximum tolerated dose of interleukin-12 (IL-12) when combined with trastuzumab in patients with HER2-Neu overexpressing malignancies. II. Determine the safety of this regimen in these patients. III. Analyze any expression of interferon-inducible genes in tumor tissues of these patients after receiving this regimen. IV. Characterize natural killer cytokine production in patients treated with this regimen. V. Determine serum interferon gamma levels in patients treated with this regimen.

OUTLINE: This is a dose escalation study of interleukin-12 (IL-12). Patients receive an initial loading dose of trastuzumab IV over 90 minutes on day 1 of the first week and a maintenance dose of trastuzumab IV over 30-90 minutes on day 1 of each subsequent week. Patients receive IL-12 IV on days 2 and 5 beginning on week 3. Treatment with maintenance trastuzumab and IL-12 repeats weekly for 14 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease continue treatment for up to 38 additional weeks. Cohorts of 3-6 patients receive escalating doses of IL-12 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 every 3 months for 1 year and then every 6 months thereafter for survival.

PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study within 6 months.

• Biological: recombinant interleukin-12
• Biological: trastuzumab

DISEASE CHARACTERISTICS: Histologically proven malignancy with overexpression of HER2-Neu (1-3+) Must have failed standard curative and/or palliative therapies Measurable or evaluable disease No concurrent brain or CNS metastases No significant prior CNS disease

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Life expectancy: At least 6 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Hemoglobin at least 9 g/dL (epoetin alfa or prior transfusion allowed) Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT and SGPT no greater than 3 times ULN Hepatitis B surface antigen negative Renal: Creatinine no greater than 1.5 times ULN Creatinine clearance at least 60 mL/min Calcium no greater than 11 mg/dL (calcium lowering agents allowed) Cardiovascular: Cardiac ejection fraction normal by echocardiogram or MUGA No active or unstable cardiovascular disease or cardiac disease requiring drug or device intervention No prior coronary artery disease No prior congestive heart failure Gastrointestinal: No clinically significant gastrointestinal bleeding No uncontrolled peptic ulcer disease No prior inflammatory bowel disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception before and during study HIV negative No other concurrent malignancy except nonmelanomatous skin cancer No significant prior peripheral neuropathy No serious concurrent infection requiring IV antibiotic therapy No clinically significant autoimmune disease (e.g., rheumatoid arthritis) No other major illness that would increase risk

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior trastuzumab Chemotherapy: At least 3 weeks since prior chemotherapy Endocrine therapy: At least 3 weeks since prior hormonal therapy No concurrent systemic corticosteroids Radiotherapy: At least 3 weeks since prior radiotherapy Surgery: At least 3 weeks since prior surgery Other: At least 3 weeks since prior investigational agents