Interferon Alfa With or Without Combination Chemotherapy Plus Interleukin-2 in Treating Patients With Melanoma

M.D. Anderson Cancer Center

Status and phase: Completed; Phase 3

Conditions: Melanoma; Skin Cancer

Treatments: Biological: Recombinant Interferon Alfa (IFN-A); Drug: Cisplatin; Drug: Vinblastine; Biological: Aldesleukin (IL-2); Drug: Dacarbazine; Procedure: Adjuvant Therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00002882

P30CA016672 (U.S. NIH Grant/Contract)

CDR0000065188 (Registry Identifier)

MDA-DM-95196 (Other Identifier)

NCI-G96-1089

ID95-196

MDA-ID-95196 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Interferon alfa may interfere with the growth of cancer cells. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. It is not yet known whether interferon alfa plus combination chemotherapy and interleukin-2 is more effective than interferon alfa alone in treating patients with melanoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of interferon alfa with or without combination chemotherapy plus interleukin-2 in treating patients with melanoma.

Full description

OBJECTIVES:

• Compare the efficacy of postoperative adjuvant therapy with interferon alfa-2b (IFN-A) administered subcutaneously with or without IV induction vs concurrent biochemotherapy including cisplatin, vinblastine, DTIC, IFN-A and IL-2 and in melanoma patients with regional lymph node metastases that have been surgically resected.
• Determine the relative toxic effects associated with adjuvant therapy with IFN-A and concurrent biochemotherapy including cisplatin, vinblastine, DTIC, IFN-A, and IL-2 and their effect on the quality of life.
• Determine the prognostic value of detection of melanoma cells in the peripheral blood using RT/PCR for tyrosinase mRNA.

OUTLINE: This is a randomized study. All patients are stratified according to prognostic factors.

Patients are randomly allocated to 1 of 2 treatment options. Treatment 1 uses interferon alfa-2b (IFN-A) therapy, and treatment 2 includes adjuvant biochemotherapy.

Patients who are randomized to IFN-A will be further stratified and randomized to one of two interferon schedules.

• Schedule A: IV IFN-A induction 5 times a week for 4 weeks followed by subcutaneous IFN-A maintenance 3 times a week for 48 weeks.
• Schedule B: Subcutaneous IFN-A 3 times a week for 52 weeks. Adjuvant biochemotherapy begins immediately after registration on the study. Cisplatin is given IV on days 1-4; vinblastine is given IVPB on days 1-4; dacarbazine (DTIC) is given IVPB on day 1; IFN-A is given subcutaneously on days 1-5; IL-2 is given by continuous infusion for a total of 96 hours on days 1-4. Each course of therapy is repeated every 21 days for 4 courses. Patients receiving adjuvant radiotherapy will start adjuvant systemic therapy within 8 weeks from lymphadenectomy and a week after completion of and recovery from radiotherapy.

PROJECTED ACCRUAL: A total of 200 patients (100 patients in each arm) will be entered.

Enrollment: 140 patients

Sex: All

Ages: 10 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically diagnosed malignant melanoma with regional lymph node metastases
• Undergone complete lymph node dissection and free of any residual tumor
• No greater than 90 days from diagnosis of regional lymph nodes metastases
• No distant or resected in-transit metastases

PATIENT CHARACTERISTICS:

Age:

• 10 to 66
• 66 to 70 if in excellent physical condition

Performance status:

• 0-2

Life expectancy:

• At least 12 months

Hematopoietic:

• Hemoglobin greater than 10 g/dL
• WBC greater than 3,000/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.2 mg/dL

Renal:

• Creatinine no greater than 1.5 mg/dL

Other:

• No serious intercurrent illness that would compromise tolerance of therapy and long term survival

• Must be able to participate in follow up for minimum of 5 years

• No second malignancy except:

  • In situ cervical cancer
  • Basal or squamous skin cancer

• Must be able to physically and emotionally tolerate biochemotherapy

• No history of pulmonary or cardiac dysfunction, e.g., cardiac rhythm disturbance, congestive heart failure, coronary bypass, or impaired cardiac ejection fraction

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy with interferon or IL-2
• No concurrent immunomodulators

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• No concurrent steroids

Radiotherapy:

• Prior adjuvant local radiotherapy allowed for head and neck

Surgery:

• No greater than 8 weeks after definitive surgery for lymph node metastases

Other:

• No concurrent nonsteroid anti-inflammatory drugs, or other prostaglandin synthetase inhibitors

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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140 participants in 3 patient groups

IFN-A Therapy Schedule A

Experimental group

Description:

Schedule A: IV Interferon alfa-2b (IFN-A) induction 5 times a week for 4 weeks followed by subcutaneous IFN-A maintenance 3 times a week for 48 weeks.

Treatment:

Biological: Recombinant Interferon Alfa (IFN-A)

IFN-A Therapy Schedule B

Experimental group

Description:

Schedule B: Subcutaneous IFN-A 3 times a week for 52 weeks.

Treatment:

Biological: Recombinant Interferon Alfa (IFN-A)

Adjuvant Biochemotherapy

Experimental group

Description:

Cisplatin IV Days 1-4; Vinblastine IVPB Days 1-4; Dacarbazine (DTIC) IVPB on Day 1; IFN-A is given subcutaneously on days 1-5; IL-2 continuous infusion for 96 hours on Days 1-4. Each course repeated every 21 days for 4 courses.

Treatment:

Drug: Vinblastine

Drug: Dacarbazine

Biological: Aldesleukin (IL-2)

Drug: Cisplatin

Biological: Recombinant Interferon Alfa (IFN-A)

Procedure: Adjuvant Therapy