RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of the cancer cells. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. It is not yet known which treatment regimen is more effective in treating melanoma. PURPOSE: Randomized phase II trial to compare the effectiveness of two regimens of combination chemotherapy plus interferon alfa and interleukin-2 in treating patients who have metastatic melanoma.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma Recurrent Melanoma	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: interferon therapy  Procedure: cytokine therapy  Procedure: interleukin therapy  Drug: cisplatin  Drug: dacarbazine  Drug: interferon alfa  Drug: interleukin-2	Phase II

Further Study Details: 

OBJECTIVES: I. Assess the rate of disease stabilization in patients with metastatic melanoma when treated with interferon alfa, dacarbazine, cisplatin, and interleukin-2. II. Assess toxicity, overall response rate, and response duration in these patients when treated with this regimen.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center. Patients are randomized to one of two treatment arms. Arm I: Patients receive dacarbazine IV over 1 hour and cisplatin IV over 3 hours on days 1-3. Patients also receive interferon alfa subcutaneously (SQ) on days 1-5 and interleukin-2 by continuous IV infusion on days 4-9. Treatment continues every 28 days for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive dacarbazine IV on day 1 and 22 every 28 days for 2 courses. Patients then receive treatment as in arm I for a maximum of 4 courses. Patients are followed every 2 months for 6 months, then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 42-90 patients will be accrued for this study.

Ages Eligible for Study:  18 Years   -   70 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed melanoma that is metastatic and unresectable
• Measurable, progressive disease (by physical exam and/or noninvasive imaging). No prior irradiation of indicator lesions.
• No CNS metastases (confirmed by CT or MRI)

--Prior/Concurrent Therapy--

Biologic therapy:

• No prior immunotherapy with interleukin-2
• No prior interferon alfa in combination with cisplatin or dacarbazine

Chemotherapy:

• No prior chemotherapy with cisplatin in combination with dacarbazine
• More than 3 months since prior chemotherapy

Endocrine therapy: Not specified

Radiotherapy: Prior radiotherapy allowed

Surgery: Not specified

--Patient Characteristics--

Age: 18 to 70

Performance status: Karnofsky 60-100%

Life expectancy: Greater than 3 months

Hematopoietic:

• WBC at least 2,500/mm3
• Platelet count at least 100,000/mm3

Hepatic: No serious hepatic disease

Renal:

• Creatinine no greater than 1.65 mg/dL
• No serious renal disease

Cardiovascular: No serious cardiac disease

Pulmonary: No serious pulmonary disease

Other:

• No organ allograft
• No autoimmune disease
• No uncontrolled infection
• No active peptic ulcer
• No hyper or hypothyroidism
• No requirement for corticosteroids
• No second malignancy except basal cell skin carcinoma or carcinoma in situ of the cervix
• Not pregnant or nursing

Austria
      Landeskrankenanstalten - Salzburg, Salzburg,  A-5020,  Austria
Belgium
      Hopital Universitaire Erasme, Brussels,  1070,  Belgium
      Institut Jules Bordet, Brussels (Bruxelles),  1000,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
France
      Centre Leon Berard, Lyon,  69373,  France
      CHR de Besancon - Hopital Saint-Jacques, Besancon,  25030,  France
      CHU Pitie-Salpetriere, Paris,  75651,  France
Germany
      Haematologisch-Onkologische Praxis Altona, Hamburg,  D-22765,  Germany
      III Medizinische Klinik Mannheim, Mannheim,  D-68135,  Germany
      Johannes Gutenberg University, Mainz,  D-55101,  Germany
      Robert Roessle Klinik, Berlin,  D-13122,  Germany
      Universitaetsklinikum Benjamin Franklin, Berlin,  D-12200,  Germany
      Universitaetsklinikum Charite, Berlin,  D-10117,  Germany
Italy
      Istituto Europeo Di Oncologia, Milano,  20141,  Italy
Netherlands
      Rotterdam Cancer Institute, Rotterdam,  3075 EA,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands
Portugal
      Instituto Portugues de Oncologia do Porto, Porto,  4200,  Portugal
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland
      Universitaetsspital, Zurich,  CH-8091,  Switzerland
United Kingdom
      Royal Bournemouth Hospital, Bournemouth,  BH7 7DW,  United Kingdom
United Kingdom, England
      Royal Marsden NHS Trust, London,  England,  SW3 6JJ,  United Kingdom
      Southend NHS Trust Hospital, Westcliff-On-Sea,  England,  United Kingdom
      St. James's Hospital, Leeds,  England,  LS9 7TF,  United Kingdom

Study chairs or principal investigators

Ulrich Keilholz,  Study Chair,  EORTC Melanoma Cooperative Group   

Study ID Numbers:  CDR0000064258; EORTC-18951
Record last reviewed:  April 2003
Last Updated:  October 13, 2004
Record first received:  June 2, 2000
ClinicalTrials.gov Identifier:  NCT00002669
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08