RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. Interferon alfa may interfere with the growth of tumor cells. It is not yet known whether combination chemotherapy plus interleukin-2 and interferon alfa is more effective than combination chemotherapy alone for metastatic melanoma.

PURPOSE: Randomized phase III trial to compare combination chemotherapy with or without interleukin-2 and interferon alfa in treating patients who have metastatic melanoma that cannot be treated by surgery.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma	Drug: cisplatin  Drug: dacarbazine  Drug: filgrastim  Drug: interferon alfa  Drug: interleukin-2  Drug: vinblastine  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: interferon therapy  Procedure: interleukin therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare response rate, duration of response, and survival rate in patients with metastatic malignant melanoma treated with cisplatin, vinblastine, and dacarbazine with or without interleukin-2 and interferon alfa-2b.
• Determine the toxic effects of these regimens in this patient population.

OUTLINE: This is a randomized study. Patients are stratified according to performance status (0 vs 1), prior interferon (yes vs no), and number of involved sites. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive cisplatin IV over 30 minutes daily immediately followed by vinblastine IV on days 1-4. Patients also receive dacarbazine IV over 60 minutes on day 1 following vinblastine.
• Arm II: Patients receive treatment as in arm I. Patients also receive interleukin 2 (IL-2) IV continuously on days 1-4 and interferon alfa-2b subcutaneously (SC) daily before IL-2 on days 1-4 and after IL-2 on day 5, followed by filgrastim (G-CSF) (SC) daily on days 7-16. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 6 weeks, every 3 months for 18 months, every 6 months for 18 months, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 482 patients will be accrued for this study within 3.5 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed surgically incurable metastatic malignant melanoma
• Measurable disease
• No active brain metastases or edema
• No leptomeningeal disease
• No ocular melanoma

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT less than 3 times the upper limit of normal unless due to liver metastases

Renal:

• Creatinine less than 1.5 mg/dL OR
• Creatinine clearance at least 75 mL/min

Cardiovascular:

• No congestive heart failure
• No symptoms of coronary artery disease
• No serious cardiac arrhythmias
• No prior myocardial infarction on EKG
• Normal cardiac stress test required for the following:
• Over 50 years of age
• Abnormal EKG
• Prior history of cardiac disease

Pulmonary:

• No symptomatic pulmonary disease
• FEV1 greater than 2.0 L OR at least 75% predicted if over 50 years of age or with history of pulmonary symptoms

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No significant infection
• HIV negative
• No other prior malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No organ allografts
• No significant disease other than malignancy
• No seizure disorder

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior interleukin-2 therapy for metastatic disease
• At least 4 weeks since prior vaccine therapy
• At least 4 weeks since prior adjuvant immunotherapy

Chemotherapy:

• No prior chemotherapy for disease

Endocrine therapy:

• No concurrent corticosteroids

Radiotherapy:

• No prior radiation therapy to measurable disease site unless disease is clearly progressive
• At least 4 weeks since prior radiation therapy for local control or palliation and recovered

Surgery:

• Recovered from prior surgery

Other:

• No prior systemic therapy for metastatic disease
• At least 3 months since definitive therapy for brain metastases

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36688,  United States
Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States
      CCOP - Greater Phoenix, Phoenix,  Arizona,  85006-2726,  United States
      Veterans Affairs Medical Center - Phoenix (Carl T. Hayden), Phoenix,  Arizona,  85012,  United States
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
      Veterans Affairs Medical Center - Little Rock (McClellan), Little Rock,  Arkansas,  72205,  United States
California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States
      University of California Davis Medical Center, Sacramento,  California,  95817,  United States
      Cancer Center and Beckman Research Institute, City of Hope, Duarte,  California,  91010-3000,  United States
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States
      Chao Family Comprehensive Cancer Center, Orange,  California,  92868,  United States
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States
      David Grant Medical Center, Travis Air Force Base,  California,  94535,  United States
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States
      Veterans Affairs Medical Center - West Los Angeles, Los Angeles,  California,  90073,  United States
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94143-0128,  United States
Colorado
      University of Colorado Cancer Center, Denver,  Colorado,  80010,  United States
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States
      Dwight David Eisenhower Army Medical Center, Fort Gordon,  Georgia,  30905-5650,  United States
Hawaii
      Cancer Research Center of Hawaii, Honolulu,  Hawaii,  96813-2424,  United States
Illinois
      Loyola University Medical Center, Maywood,  Illinois,  60153,  United States
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States
      Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital), Hines,  Illinois,  60141,  United States
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612-7323,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7353,  United States
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States
Kentucky
      Albert B. Chandler Medical Center, University of Kentucky, Lexington,  Kentucky,  40536-0084,  United States
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40502-2236,  United States
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71130,  United States
Massachusetts
      Boston Medical Center, Boston,  Massachusetts,  02118,  United States
      Veterans Affairs Medical Center - Boston (Jamaica Plain), Jamaica Plain,  Massachusetts,  02130,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
      Providence Hospital - Southfield, Southfield,  Michigan,  48075-9975,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0912,  United States
      Veterans Affairs Medical Center - Ann Arbor, Ann Arbor,  Michigan,  48105,  United States
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States
      CCOP - Ann Arbor Regional, Ann Arbor,  Michigan,  48106,  United States
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
      Keesler Medical Center - Keesler AFB, Keesler AFB,  Mississippi,  39534-2576,  United States
      Veterans Affairs Medical Center - Biloxi, Biloxi,  Mississippi,  39531-2410,  United States
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States
      St. Louis University Health Sciences Center, Saint Louis,  Missouri,  63110,  United States
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States
      Veterans Affairs Medical Center - Kansas City, Kansas City,  Missouri,  64128,  United States
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States
New York
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States
      Veterans Affairs Medical Center - Albany, Albany,  New York,  12208,  United States
      University of Rochester Medical Center, Rochester,  New York,  14642,  United States
North Carolina
      CCOP - Southeast Cancer Control Consortium, Winston Salem,  North Carolina,  27104-4241,  United States
Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States
      CCOP - Dayton, Kettering,  Ohio,  45429,  United States
      Barrett Cancer Center, The University Hospital, Cincinnati,  Ohio,  45267-0501,  United States
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428,  United States
      CCOP - Toledo Community Hospital Oncology Program, Toledo,  Ohio,  43623-3456,  United States
Oklahoma
      Oklahoma Medical Research Foundation, Oklahoma City,  Oklahoma,  73104,  United States
      Veterans Affairs Medical Center - Oklahoma City, Oklahoma City,  Oklahoma,  73104,  United States
Oregon
      OHSU Cancer Institute, Portland,  Oregon,  97239,  United States
      CCOP - Columbia River Program, Portland,  Oregon,  97225,  United States
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States
South Carolina
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States
      Veterans Affairs Medical Center - Charleston, Charleston,  South Carolina,  29401-5799,  United States
Texas
      University of Texas Medical Branch, Galveston,  Texas,  77555-0565,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78284-7845,  United States
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234-6200,  United States
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78284,  United States
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States
      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-8852,  United States
      Veterans Affairs Medical Center - Houston, Houston,  Texas,  77030,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112-5550,  United States
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States
Washington
      Swedish Cancer Institute, Seattle,  Washington,  98104,  United States
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States
      Madigan Army Medical Center, Tacoma,  Washington,  98431-5048,  United States

Study chairs or principal investigators

Michael Benjamin Atkins, MD,  Study Chair,  New England Medical Center   
Lawrence E. Flaherty, MD,  Study Chair,  Barbara Ann Karmanos Cancer Institute   
David M. Gustin, MD,  Study Chair,  Lutheran General Hospital   

Study ID Numbers:  CDR0000065617; E-E3695; CLB-509802; SWOG-E3695
Record last reviewed:  February 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003027
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08