Combination Chemotherapy, Interferon Alfa, and Interleukin-2 in Treating Patients With Metastatic Melanoma

NCT ID: NCT00002669

Last Updated: 2012-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1995-06-30

Brief Summary

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.

Detailed Description

OBJECTIVES:

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

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.

Conditions

Melanoma (Skin)

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

aldesleukin

Intervention Type: BIOLOGICAL

recombinant interferon alfa

Intervention Type: BIOLOGICAL

cisplatin

Intervention Type: DRUG

dacarbazine

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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)

PATIENT CHARACTERISTICS:

Age:

• 18 to 70

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Greater than 3 months

Hematopoietic:

• WBC at least 2,500/mm^3
• Platelet count at least 100,000/mm^3

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ulrich Keilholz, MD

Role: STUDY_CHAIR

Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

Locations

Landeskrankenanstalten - Salzburg

Salzburg, , Austria

Hopital Universitaire Erasme

Brussels, , Belgium

Institut Jules Bordet

Brussels (Bruxelles), , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

U.Z. Gasthuisberg

Leuven, , Belgium

CHR de Besancon - Hopital Saint-Jacques

Besançon, , France

Centre Leon Berard

Lyon, , France

CHU Pitie-Salpetriere

Paris, , France

Universitaetsklinikum Charite

Berlin, , Germany

Universitaetsklinikum Benjamin Franklin

Berlin, , Germany

Robert Roessle Klinik

Berlin, , Germany

Haematologisch-Onkologische Praxis Altona

Hamburg, , Germany

Johannes Gutenberg University

Mainz, , Germany

III Medizinische Klinik Mannheim

Mannheim, , Germany

Istituto Europeo Di Oncologia

Milan, , Italy

University Medical Center Nijmegen

Nijmegen, , Netherlands

Rotterdam Cancer Institute

Rotterdam, , Netherlands

Instituto Portugues de Oncologia do Porto

Porto, , Portugal

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Universitaetsspital

Zurich, , Switzerland

St. James's Hospital

Leeds, England, United Kingdom

Royal Marsden NHS Trust

London, England, United Kingdom

Southend NHS Trust Hospital

Westcliff-on-Sea, England, United Kingdom

Royal Bournemouth Hospital

Bournemouth, , United Kingdom

Countries

Austria; Belgium; France; Germany; Italy; Netherlands; Portugal; Switzerland; United Kingdom

References

Agarwala SS, Keilholz U, Gilles E, Bedikian AY, Wu J, Kay R, Stein CA, Itri LM, Suciu S, Eggermont AM. LDH correlation with survival in advanced melanoma from two large, randomised trials (Oblimersen GM301 and EORTC 18951). Eur J Cancer. 2009 Jul;45(10):1807-14. doi: 10.1016/j.ejca.2009.04.016. Epub 2009 May 4.

Reference Type: BACKGROUND

PMID: 19419855 (View on PubMed)

Keilholz U, Suciu S, Bedikian AY, et al.: LDH is a prognostic factor in stage IV melanoma patients (pts) but is a predictive factor only for bcl2 antisense treatment efficacy: re-analysis of GM301 and EORTC18951 randomized trials. [Abstract] J Clin Oncol 25 (Suppl 18): A-8552, 485s, 2007.

Reference Type: BACKGROUND

Keilholz U, Eggermont AM. The role of interleukin-2 in the management of stage IV melanoma: the EORTC melanoma cooperative group program. Cancer J Sci Am. 2000 Feb;6 Suppl 1:S99-103.

Reference Type: BACKGROUND

PMID: 10685668 (View on PubMed)

Schmidt H, Suciu S, Punt CJ, Gore M, Kruit W, Patel P, Lienard D, von der Maase H, Eggermont AM, Keilholz U; American Joint Committee on Cancer Stage IV Melanoma; EORTC 18951. Pretreatment levels of peripheral neutrophils and leukocytes as independent predictors of overall survival in patients with American Joint Committee on Cancer Stage IV Melanoma: results of the EORTC 18951 Biochemotherapy Trial. J Clin Oncol. 2007 Apr 20;25(12):1562-9. doi: 10.1200/JCO.2006.09.0274.

Reference Type: RESULT

PMID: 17443000 (View on PubMed)

Punt CJ, Suciu S, Gore MA, Koller J, Kruit WH, Thomas J, Patel P, Lienard D, Eggermont AM, Keilholz U. Chemoimmunotherapy with dacarbazine, cisplatin, interferon-alpha2b and interleukin-2 versus two cycles of dacarbazine followed by chemoimmunotherapy in patients with metastatic melanoma: a randomised phase II study of the European Organization for Research and Treatment of Cancer Melanoma Group. Eur J Cancer. 2006 Nov;42(17):2991-5. doi: 10.1016/j.ejca.2006.08.012. Epub 2006 Oct 4.

Reference Type: RESULT

PMID: 17023156 (View on PubMed)

Keilholz U, Punt CJ, Gore M, Kruit W, Patel P, Lienard D, Thomas J, Proebstle TM, Schmittel A, Schadendorf D, Velu T, Negrier S, Kleeberg U, Lehman F, Suciu S, Eggermont AM. Dacarbazine, cisplatin, and interferon-alfa-2b with or without interleukin-2 in metastatic melanoma: a randomized phase III trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group. J Clin Oncol. 2005 Sep 20;23(27):6747-55. doi: 10.1200/JCO.2005.03.202.

Reference Type: RESULT

PMID: 16170182 (View on PubMed)

Keilholz U, Punt CJ, Gore M, et al.: Dacarbazine, cisplatin and interferon alpha with or without interleukin-2 in advanced melanoma: interim analysis of EORTC trial 18951. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A2043, 530a, 1999.

Reference Type: RESULT

Other Identifiers

EORTC-18951

Identifier Type: -

Identifier Source: secondary_id

EORTC-18951

Identifier Type: -

Identifier Source: org_study_id