interleukin-12 and interferon alfa in treating patients with metastatic malignant melanoma

Conditions: Recurrent Melanoma; Stage IV Melanoma

Summary: phase ii trial to study the effectiveness of combining interleukin-12 and interferon alfa in treating patients who have metastatic malignant melanoma. 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. interferon alfa may interfere with the growth of the cancer cells. combining interleukin-12 and interferon alfa may kill more tumor cells.

primary objectives: i. to estimate the clinical response rates in patients with metastatic malignant melanoma treated with rhil-12 and interferon alfa-2b. ii. to estimate the progression-free survival in patients with metastatic malignant melanoma treated with rhil-12 and interferon alfa-2b. secondary objectives: i. to measure serum levels of interferon-gamma. ii. to measure levels of jak-stat signaling intermediates in patient pbmcs and tumor samples. iii. to analyze interferon-alpha-induced stat signaling in patient pbmcs. iv. to determine the expression of ifn-regulated genes in patient pbmcs and tumor tissues. v. to determine the pattern of gene expression induced by treatment with il-12 and interferon-alpha using dna microarray techniques in patient pbmcs. outline: this is a multicenter study. patients receive interleukin-12 iv over 5-15 seconds on day 1 and interferon alfa subcutaneously on days 2-6. treatment repeats every 2 weeks in the absence of unacceptable toxicity. patients are reassessed after 6 courses. patients with a complete response receive 2 additional courses. patients with a partial response or stable disease continue treatment in the absence of disease progression. patients are followed every 3 months for 1 year and then every 6 months for 1 year.

Eligibility criteria:
inclusion criteria: * histological or cytological diagnosis of cutaneous melanoma and clinical evidence of distant, metastatic, non-resectable regional lymphatic, or extensive in transit recurrent disease * patients must have measurable disease; measurable disease is defined as the presence of at least one measurable lesion; if the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology; measurable lesions are defined as lesions that can be accurately measured in at least one dimension with the longest diameter \>= 20 mm using conventional techniques or \>= 10 mm with spiral ct scan * lesions that are considered intrinsically non-measurable include the following: * bone lesions; * leptomeningeal disease; * ascites; * pleural/pericardial effusion; * inflammatory breast disease; * lymphangitis cutis/pulmonis; * abdominal masses that are not confirmed and followed by imaging techniques; * lytic lesions; * lesions that are situated in a previously irradiated area * no history of peripheral neuropathy, brain metastases or other central nervous system disease * no history of/active autoimmune disease, hemolytic anemia or concurrent requirement for corticosteroids, including topical or inhaled * no hepatitis bsag, known hiv disease or other major active illness; patients with risk factors for hiv should be tested; patients with these illnesses are more likely to experience significant side effects from the study treatment * no history of severe peptic ulcer disease or gastrointestinal bleeding unless there is objective evidence that the condition is inactive or resolved * no uncontrolled or severe cardiovascular disease, diabetes, pulmonary disease, or infection * no chemotherapy, radiotherapy, or anti-hormonal therapy within three weeks prior to the initiation of therapy on this study * no prior therapy with il-12 * no prior therapy with ifn-alpha for metastatic disease (e.g., biochemotherapy); prior adjuvant therapy with ifn-a is acceptable as long as the patient remained disease-free for 12 months or longer following the last ifn-a treatment * no prior cytokine therapy for metastatic disease (e.g., high-dose il-2) * no more than one prior chemotherapy regimen * ctc (ecog) performance status 0-1 * non-pregnant, non-nursing; treatment under this protocol would expose an unborn child to significant risks; women and men of reproductive potential should agree to use an effective means of birth control; women of child-bearing age will undergo pregnancy testing * anc \>= 1500/μl * platelets \>= 100,000/μl * hemoglobin \> 9 g/dl (may be post transfusion or may receive epo) * u-hcg or serum hcg negative (if patient of child-bearing potential)