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

Melanoma (Skin) Clinical Trial

Official title:

TREATMENT OF METASTATIC MELANOMA WITH DTIC, CDDP AND IFN ALPHA WITH OR WITHOUT IL-2: A RANDOMIZED PHASE III TRIAL

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002669
• Other study ID #: EORTC-18951
• Secondary ID: EORTC-18951
• Status: Completed
• Phase: Phase 2
• First received: June 2, 2000
• Last updated: June 29, 2012
• Start date: June 1995

Study information

• Verified date: June 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. primary completion date: August 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• aldesleukin

• recombinant interferon alfa

Drug:
• cisplatin

• dacarbazine

Locations

Country	Name	City	State
Austria	Landeskrankenanstalten - Salzburg	Salzburg
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Institut Jules Bordet	Brussels (Bruxelles)
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	U.Z. Gasthuisberg	Leuven
France	CHR de Besancon - Hopital Saint-Jacques	Besancon
France	Centre Leon Berard	Lyon
France	CHU Pitie-Salpetriere	Paris
Germany	Robert Roessle Klinik	Berlin
Germany	Universitaetsklinikum Benjamin Franklin	Berlin
Germany	Universitaetsklinikum Charite	Berlin
Germany	Haematologisch-Onkologische Praxis Altona	Hamburg
Germany	Johannes Gutenberg University	Mainz
Germany	III Medizinische Klinik Mannheim	Mannheim
Italy	Istituto Europeo Di Oncologia	Milano
Netherlands	University Medical Center Nijmegen	Nijmegen
Netherlands	Rotterdam Cancer Institute	Rotterdam
Portugal	Instituto Portugues de Oncologia do Porto	Porto
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Universitaetsspital	Zurich
United Kingdom	Royal Bournemouth Hospital	Bournemouth
United Kingdom	St. James's Hospital	Leeds	England
United Kingdom	Royal Marsden NHS Trust	London	England
United Kingdom	Southend NHS Trust Hospital	Westcliff-On-Sea	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

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

References & Publications (7)

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. — View Citation

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. — View Citation

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

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 m — View Citation

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.

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 — View Citation

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 pre — View Citation