Interleukin-12 and Interferon Alfa in Treating Patients With Metastatic Malignant Melanoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Trial of Interleukin-12 (NSC #672423, IND #6798) Followed by Interferon Alfa-2B in Patients With Metastatic Malignant Melanoma

Conditions
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Recurrent Melanoma, Stage IV Melanoma

Intervention / Treatment
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* Biological: recombinant interleukin-12
* Biological: recombinant interferon alfa
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Biological: recombinant interleukin-12<br>* Given IV<br>* Other names: Ro 24-7472;Biological: recombinant interferon alfa<br>* Given SC<br>* Other names: Roferon-A;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | Up to 2 years | 
| PFS |  | From registration until time of documented progression of disease or death from any cause, assessed up to 2 years |