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Combination Chemotherapy With or Without Interleukin-2 and Interferon Alfa in Treating Patients With Metastatic Melanoma
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: Eastern Cooperative Oncology Group
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)
Drug: aldesleukin
Drug: cisplatin
Drug: dacarbazine
Drug: filgrastim
Drug: recombinant interferon alfa
Drug: vinblastine
Phase III

MedlinePlus related topics: Cancer Melanoma
Drug Information available for: Filgrastim Cisplatin Aldesleukin Dacarbazine Interferon alfa-n1 Interferon alfa-2a Interferons Vinblastine Vinblastine sulfate Interleukin-2
U.S. FDA Resources
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

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
Estimated Primary Completion Date: August 1999 (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

  Show 94 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Southwest Oncology Group
Cancer and Leukemia Group B
Investigators
Study Chair: Michael B. Atkins, MD Tufts-NEMC Cancer Center
Study Chair: Lawrence E. Flaherty, MD Barbara Ann Karmanos Cancer Institute
Study Chair: David M. Gustin, MD University of Illinois
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
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: November 18, 2008
ClinicalTrials.gov Identifier: NCT00003027  
Health Authority: United States: Federal Government

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

Study placed in the following topic categories:
Interferon-alpha
Interferon Type I, Recombinant
Dacarbazine
Interferons
Vinblastine
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Aldesleukin
Cisplatin
Interleukin-2
Neoplasms, Germ Cell and Embryonal
Nevus, Pigmented
Neuroepithelioma
Nevus
Interferon Alfa-2a

Additional relevant MeSH terms:
Anti-Infective Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Anti-Retroviral Agents
Therapeutic Uses
Nevi and Melanomas
Angiogenesis Modulating Agents
Growth Inhibitors
Alkylating Agents
Neoplasms by Histologic Type
Anti-HIV Agents
Growth Substances
Mitosis Modulators
Antimitotic Agents
Angiogenesis Inhibitors
Antiviral Agents
Pharmacologic Actions
Neoplasms
Radiation-Sensitizing Agents
Tubulin Modulators
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 14, 2009