Patient case: 49-year-old male with melanoma; genetic feature: extensive tumor infiltrating lymphocytes

Clinical trial: Interleukin-12 and Interferon Alfa in Treating Patients With Metastatic Malignant 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.

Detailed description: 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: 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)

Relevance to patient case: not relevant