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

Phase 2
Completed
Conditions
Recurrent Melanoma
Stage IV Melanoma
Interventions
Biological: recombinant interleukin-12
Biological: recombinant interferon alfa
Other: laboratory biomarker analysis
Registration Number
NCT00026143
Lead Sponsor
National Cancer Institute (NCI)
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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)

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Arm Irecombinant interleukin-12Patients 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.
Arm Irecombinant interferon alfaPatients 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.
Arm Ilaboratory biomarker analysisPatients 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.
Primary Outcome Measures
NameTimeMethod
Response rateUp to 2 years
PFSFrom registration until time of documented progression of disease or death from any cause, assessed up to 2 years
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Cancer and Leukemia Group B

🇺🇸

Chicago, Illinois, United States

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