Clinical trial NCT00002669: Combination Chemotherapy, Interferon Alfa, and Interleukin-2 in Treating Patients With Metastatic Melanoma
Official title: TREATMENT OF METASTATIC MELANOMA WITH DTIC, CDDP AND IFN ALPHA WITH OR WITHOUT IL-2: A RANDOMIZED PHASE III TRIAL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma (Skin)
Keywords: stage IV melanoma
recurrent melanoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-04-11
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Salzburg
country: Austria
facility: Landeskrankenanstalten - Salzburg
city: Brussels (Bruxelles)
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Besancon
country: France
facility: CHR de Besancon - Hopital Saint-Jacques
city: Lyon
country: France
facility: Centre Leon Berard
city: Paris
country: France
facility: CHU Pitie-Salpetriere
city: Berlin
country: Germany
facility: Universitaetsklinikum Charite
city: Berlin
country: Germany
facility: Universitaetsklinikum Benjamin Franklin
city: Berlin
country: Germany
facility: Robert Roessle Klinik
city: Hamburg
country: Germany
facility: Haematologisch-Onkologische Praxis Altona
city: Mainz
country: Germany
facility: Johannes Gutenberg University
city: Mannheim
country: Germany
facility: III Medizinische Klinik Mannheim
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen
city: Rotterdam
country: Netherlands
facility: Rotterdam Cancer Institute
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Zurich
country: Switzerland
facility: Universitaetsspital
city: Leeds
country: United Kingdom
facility: St. James's Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden NHS Trust
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend NHS Trust Hospital
state: England
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
Study officials:
affiliation: Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
name: Ulrich Keilholz, MD
role: STUDY_CHAIR
References:
citation: 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.
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.
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.
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 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.
citation: 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.
citation: 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.
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, 1999.