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

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

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Melanoma; Stage IV Melanoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Biological: recombinant interleukin-12; Biological: recombinant interferon alfa

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60606
      • Cancer and Leukemia Group B

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Arm I; 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.

Other: laboratory biomarker analysis; Correlative studies; Biological: recombinant interleukin-12; Given IV; Other Names: cytotoxic lymphocyte maturation factor; IL-12; interleukin-12; natural killer cell stimulatory factor; Ro 24-7472; Biological: recombinant interferon alfa; Given SC; Other Names: Roferon-A; Intron A; alpha interferon; IFN-A; Alferon N

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: William Carson, Cancer and Leukemia Group B

Study record dates

Study Major Dates

• Study Start: October 1, 2001
• Primary Completion (Actual): July 1, 2004

Study Registration Dates

• First Submitted: November 9, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 5, 2013
• Last Update Submitted That Met QC Criteria: June 4, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Adjuvants, Immunologic; Interferons; Interferon-alpha; Interferon alpha-2; Interleukin-12
• Other Study ID Numbers: NCI-2012-02816; U10CA031946 (U.S. NIH Grant/Contract); CALGB-500001; CDR0000068990