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Combination Chemotherapy With or Without Interleukin-2 and Interferon Alfa in Treating Patients With Metastatic Melanoma
This study has been completed.
First Received: November 1, 1999   Last Updated: May 29, 2009   History of Changes
Sponsor: Eastern Cooperative Oncology Group
Collaborators: National Cancer Institute (NCI)
Southwest Oncology Group
Cancer and Leukemia Group B
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003027
  Purpose

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 Intervention Phase
Melanoma (Skin)
Biological: aldesleukin
Biological: filgrastim
Biological: recombinant interferon alfa
Drug: cisplatin
Drug: dacarbazine
Drug: vinblastine
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: A Randomized Phase III Trial of Concurrent Biochemotherapy With Cisplatin, Vinblastine, Dacarbazine, IL-2 and Interferon A-2B Versus Cisplatin, Vinblastine, Dacarbazine Alone in Patients With Metastatic Malignant Melanoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate (complete and partial response) [ Designated as safety issue: No ]
  • Durable complete response rate [ Designated as safety issue: No ]
  • Response duration [ Designated as safety issue: No ]

Estimated Enrollment: 482
Study Start Date: October 1997
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003027

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

Additional Information:
Publications:
Atkins MB, Hsu J, Lee S, Cohen GI, Flaherty LE, Sosman JA, Sondak VK, Kirkwood JM. Phase III Trial Comparing Concurrent Biochemotherapy With Cisplatin, Vinblastine, Dacarbazine, Interleukin-2, and Interferon Alfa-2b With Cisplatin, Vinblastine, and Dacarbazine Alone in Patients With Metastatic Malignant Melanoma (E3695): A Trial Coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2008 Nov 10; [Epub ahead of print]
Atkins MB, Lee S, Flaherty LE: A prospective randomized phase III trial of concurrent biochemotherapy (BCT) with cisplatin, vinblastine, dacarbazine (CVD), IL-2 and interferon alpha-2b (IFN) versus CVD alone in patients with metastatic melanoma (E3695): an ECOG-coordinated intergroup trial. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2847, 2003.

Study ID Numbers: CDR0000065617, E-E3695, CLB-509802, SWOG-E3695
Study First Received: November 1, 1999
Last Updated: May 29, 2009
ClinicalTrials.gov Identifier: NCT00003027     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage IV melanoma

Additional relevant MeSH terms:
Anti-Infective Agents
Interferon Type I, Recombinant
Dacarbazine
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Vinblastine
Melanoma
Anti-Retroviral Agents
Cisplatin
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Nevi and Melanomas
Growth Inhibitors
Angiogenesis Modulating Agents
Alkylating Agents
Interferon-alpha
Anti-HIV Agents
Neoplasms by Histologic Type
Growth Substances
Mitosis Modulators
Interferons
Antimitotic Agents
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Neuroendocrine Tumors
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on November 27, 2009