High-Dose or Low-Dose Interferon Alfa Compared With No Further Therapy Following Surgery in Treating Patients With Stage III Melanoma

NCT ID: NCT00002763

Last Updated: 2011-11-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

1000 participants

Study Classification

INTERVENTIONAL

Study Start Date

1996-04-30

Brief Summary

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RATIONALE: Interferon alfa may interfere with the growth of cancer cells. It is not known whether giving high-dose or low-dose interferon alfa is more effective than no further therapy in treating patients with stage III melanoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of high- or low-dose interferon alfa with that of no further therapy following surgery in treating patients who have stage III melanoma.

Detailed Description

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OBJECTIVES: I. Evaluate the time to distant metastasis, death due to melanoma, and overall survival in patients with high-risk stage III melanoma treated with 10 MU of interferon alfa (IFN-A) for 4 weeks followed by 1 year of IFN-A at 10 MU three times per week vs. 2 years of IFN-A at 5 MU three times per week vs. observation alone. II. Assess the toxicity associated with IFN-A. III. Compare the quality of life, costs, and compliance associated with each treatment regimen.

OUTLINE: Randomized study. Following definitive surgical resection, patients are randomly assigned in a 2:2:1 ratio to Arms A, B, and C, respectively. Arm A: Biological Response Modifier Therapy. Interferon alfa-2b (Schering), IFN-A, NSC-377523. Higher dose. Arm B: Biological Response Modifier Therapy. IFN-A. Lower dose. Arm C: Control. Observation.

PROJECTED ACCRUAL: A total of 1,000 patients will be entered over approximately 4 years in this multicenter study.

Conditions

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Melanoma (Skin)

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

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recombinant interferon alfa

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS: Cutaneous melanoma in one of the following categories: T4, N0, M0 Deep primary tumor with Breslow depth greater than 4.0 cm Tx, N1, M0 Primary tumor with regional lymph node metastases found at lymphadenectomy but clinically undetectable Tx, N2, M0 Clinically apparent regional lymph node metastases (synchronous or metachronous) confirmed by lymphadenectomy Definitive surgical resection and lymphadenectomy with pathologically confirmed adequate surgical margins required Minimum 2 cm margin for primary lesions with Breslow depth greater than 2 mm Distal interphalangeal amputation required for subungual melanomas No primary melanoma originating apart from the skin No multiple in transit metastases in an extremity No lymph node involvement outside the operative area resected by radical neck, axillary lymph node, or ilioinguinal dissection

PATIENT CHARACTERISTICS: Age: 16 to 75 Performance status: ECOG 0 or 1 Hematopoietic: WBC at least 4,000 Platelets at least 125,000 Hemoglobin at least 9.8 g/dL (6.1 mmol/L) Hepatic: Bilirubin no greater than 2 times normal AST no greater than 2 times normal Renal: Creatinine no greater than 1.6 mg/dL (140 micromoles/L) Cardiovascular: No ventricular or supraventricular arrhythmia requiring treatment No congestive heart failure (NYHA class 3/4 status) Other: No uncontrolled infection No requirement for ongoing steroids, NSAIDs, or other immunomodulators No organic brain syndrome or significant impairment of basal cognitive function No psychiatric disorder that would preclude study participation or would be exacerbated by study therapy (e.g., depression) No second malignancy except: In situ cervical cancer Nonmelanomatous skin cancer No pregnant or nursing women

PRIOR CONCURRENT THERAPY: No prior treatment on this protocol for patients with recurrent melanoma at regional lymph nodes No preoperative infusion or perfusion therapy Biologic therapy: No prior adjuvant immunotherapy Chemotherapy: No prior adjuvant systemic chemotherapy No prior anthracyclines Endocrine therapy: Not specified Radiotherapy: No prior adjuvant radiotherapy Surgery: See Disease Characteristics
Minimum Eligible Age

16 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role lead

Principal Investigators

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Alexander M. M. Eggermont, MD, PhD

Role: STUDY_CHAIR

Daniel Den Hoed Cancer Center at Erasmus Medical Center

Locations

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Krankenhaus der Elisabethinen

Linz, , Austria

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Landeskrankenanstalten - Salzburg

Salzburg, , Austria

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Hopital Universitaire Erasme

Brussels, , Belgium

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Institut Jules Bordet

Brussels (Bruxelles), , Belgium

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Cliniques Universitaires Saint-Luc

Brussels (Bruxelles), , Belgium

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Centre Hospitalier Notre Dame - Reine Fabiola

Charleroi, , Belgium

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Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

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Universitair Ziekenhuis Gent

Ghent (Gent), , Belgium

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U.Z. Gasthuisberg

Leuven, , Belgium

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Alexander's University Hospital

Sofia, , Bulgaria

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National Centre of Oncology

Sofia, , Bulgaria

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University Hospital Sestre Milosrdnice

Zagreb, , Croatia

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Estonian Cancer Center

Tallinn, , Estonia

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Tampere University Hospital

Tampere, , Finland

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Turku University Central Hospital

Turku, , Finland

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CHU de Bordeaux - Hopital Pellegrin

Bordeaux, , France

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Institut Bergonie

Bordeaux, , France

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CHU Ambroise Pare

Boulogne-Billancourt, , France

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CHRU de Caen

Caen, , France

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Centre Leon Berard

Lyon, , France

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Centre Antoine Lacassagne

Nice, , France

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Hopital L'Archet - 2

Nice, , France

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Hopital Bichat-Claude Bernard

Paris, , France

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Hopital Saint-Louis

Paris, , France

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Hopital Cochin

Paris, , France

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Hopital Haut Leveque

Pessac, , France

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Centre Eugene Marquis

Rennes, , France

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Centre Rene Huguenin

Saint-Cloud, , France

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Centre Hospitalier Regional et Universitaire de Saint-Etienne

Saint-Priest-en-Jarez, , France

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Hopitaux Universitaire de Strasbourg

Strasbourg, , France

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Centre Hospitalier Regional Metz Thionville

Thionville, , France

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Institut Claudius Regaud

Toulouse, , France

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Centre Hospitalier Universitaire Bretonneau de Tours

Tours, , France

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Institut Gustave Roussy

Villejuif, , France

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Universitaetsklinikum Benjamin Franklin

Berlin, , Germany

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Robert Roessle Klinik

Berlin, , Germany

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Universitaets-Augenklinik - Erlangen

Erlangen, , Germany

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Georg August Universitaet

Göttingen, , Germany

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Universitats-Krankenhaus Eppendorf

Hamburg, , Germany

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Haematologisch-Onkologische Praxis Altona

Hamburg, , Germany

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Department of Dematology, Hannover Medical School

Hanover, , Germany

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Universitaets-Hautklinik Heidelberg

Heidelberg, , Germany

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Universitatsklinik, Saarland

Homburg/Saar, , Germany

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III Medizinische Klinik Mannheim

Mannheim, , Germany

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Klinikum der Universitat Regensburg

Regensburg, , Germany

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Universitatshautklinik Eberhard - Karlsuniversitat Tubingen

Tübingen, , Germany

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Department of Dermatology

Ulm, , Germany

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Universitaet Wuerzburg/Hautkrankheiten

Würzburg, , Germany

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Wolfson Medical Center

Holon, , Israel

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Tel-Aviv Medical Center-Ichilov Hospital

Tel Aviv, , Israel

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Istituto Europeo Di Oncologia

Milan, , Italy

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Academisch Ziekenhuis der Vrije Universiteit

Amsterdam, , Netherlands

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Antoni van Leeuwenhoekhuis

Amsterdam, , Netherlands

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Academisch Ziekenhuis Groningen

Groningen, , Netherlands

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Leiden University Medical Center

Leiden, , Netherlands

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University Medical Center Nijmegen

Nijmegen, , Netherlands

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Rotterdam Cancer Institute

Rotterdam, , Netherlands

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Academisch Ziekenhuis Utrecht

Utrecht, , Netherlands

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Medical University of Gdansk

Gdansk, , Poland

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Maria Sklodowska-Curie M.C.C.I.O. Krakow

Krakow (Cracow), , Poland

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Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, , Poland

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Instituto Portugues de Oncologia de Francisco Gentil

Lisbon, , Portugal

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Instituto Portugues de Oncologia do Porto

Porto, , Portugal

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Russian Academy of Medical Sciences Cancer Research Center

Moscow, , Russia

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Institute of Oncology and Radiology of Serbia

Belgrade, , Serbia

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National Cancer Institute - Bratislava

Bratislava, , Slovakia

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Hospital Clinic y Provincial de Barcelona

Barcelona, , Spain

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Hospital Clinico Universitario

Zaragoza, , Spain

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Huddinge Hospital

Huddinge, , Sweden

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Ospedale San Giovanni

Bellinzona, , Switzerland

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Inselspital, Bern

Bern, , Switzerland

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Ratisches Kantons und Regionalspital

Chur, , Switzerland

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Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

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Kantonsspital - Saint Gallen

Sankt Gallen, , Switzerland

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Universitaetsspital

Zurich, , Switzerland

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Cukurova University School of Medicine

Adana, , Turkey (Türkiye)

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Vakif Gureba Training Hospital

Istanbul, , Turkey (Türkiye)

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Istanbul University-Institute of Oncology

Istanbul, , Turkey (Türkiye)

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Cerrahpasa Medical School

Istanbul, , Turkey (Türkiye)

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Ege University Medical School

Izmir, , Turkey (Türkiye)

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Bristol Oncology Centre

Bristol, England, United Kingdom

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Addenbrooke's NHS Trust

Cambridge, England, United Kingdom

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St. James's Hospital

Leeds, England, United Kingdom

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Royal Marsden NHS Trust

London, England, United Kingdom

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Derriford Hospital

Plymouth, England, United Kingdom

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Beatson Oncology Centre

Glasgow, Scotland, United Kingdom

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Countries

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Austria Belgium Bulgaria Croatia Estonia Finland France Germany Israel Italy Netherlands Poland Portugal Russia Serbia Slovakia Spain Sweden Switzerland Turkey (Türkiye) United Kingdom

References

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Eggermont AM, Suciu S, Testori A, Kruit WH, Marsden J, Punt CJ, Santinami M, Sales F, Schadendorf D, Patel P, Dummer R, Robert C, Keilholz U, Yver A, Spatz A. Ulceration and stage are predictive of interferon efficacy in melanoma: results of the phase III adjuvant trials EORTC 18952 and EORTC 18991. Eur J Cancer. 2012 Jan;48(2):218-25. doi: 10.1016/j.ejca.2011.09.028. Epub 2011 Nov 5.

Reference Type BACKGROUND
PMID: 22056637 (View on PubMed)

Bouwhuis MG, Suciu S, Collette S, Aamdal S, Kruit WH, Bastholt L, Stierner U, Sales F, Patel P, Punt CJ, Hernberg M, Spatz A, ten Hagen TL, Hansson J, Eggermont AM; EORTC Melanoma Group and the Nordic Melanoma Group. Autoimmune antibodies and recurrence-free interval in melanoma patients treated with adjuvant interferon. J Natl Cancer Inst. 2009 Jun 16;101(12):869-77. doi: 10.1093/jnci/djp132. Epub 2009 Jun 9.

Reference Type BACKGROUND
PMID: 19509353 (View on PubMed)

Eggermont AM, Punt CJ. Does adjuvant systemic therapy with interferon-alpha for stage II-III melanoma prolong survival? Am J Clin Dermatol. 2003;4(8):531-6. doi: 10.2165/00128071-200304080-00002.

Reference Type BACKGROUND
PMID: 12862495 (View on PubMed)

Bouwhuis MG, Collette S, Suciu S, de Groot ER, Kruit WH, Ten Hagen TL, Aarden LA, Eggermont AM, Swaak AJ; EORTC Melanoma Group. Changes of ferritin and CRP levels in melanoma patients treated with adjuvant interferon-alpha (EORTC 18952) and prognostic value on treatment outcome. Melanoma Res. 2011 Aug;21(4):344-51. doi: 10.1097/CMR.0b013e328346c17f.

Reference Type RESULT
PMID: 21546857 (View on PubMed)

Bouwhuis MG, Suciu S, Kruit W, Sales F, Stoitchkov K, Patel P, Cocquyt V, Thomas J, Lienard D, Eggermont AM, Ghanem G; European Organisation for Research and Treatment of Cancer Melanoma Group. Prognostic value of serial blood S100B determinations in stage IIB-III melanoma patients: a corollary study to EORTC trial 18952. Eur J Cancer. 2011 Feb;47(3):361-8. doi: 10.1016/j.ejca.2010.10.005. Epub 2010 Nov 17.

Reference Type RESULT
PMID: 21087856 (View on PubMed)

Bouwhuis M, Suciu S, Kruit W, et al.: Prognostic value of autoantibodies (auto-AB) in melanoma patients (pts) in the EORTC 18952 trial of adjuvant interferon (IFN) compared to observation (obs). [Abstract] J Clin Oncol 25 (Suppl 18): A-8507, 473s, 2007.

Reference Type RESULT

Suciu S, Ghanem G, Kruit W, et al.: Serum S-100B protein is a strong independent prognostic marker for distant-metastasis free survival (DMFS) in stage III melanoma patients: an evaluation of the EORTC randomized trial 18952 comparing IFNα versus observation. [Abstract] J Clin Oncol 25 (Suppl 18): A-8518, 476s, 2007.

Reference Type RESULT

Eggermont AM, Suciu S, MacKie R, Ruka W, Testori A, Kruit W, Punt CJ, Delauney M, Sales F, Groenewegen G, Ruiter DJ, Jagiello I, Stoitchkov K, Keilholz U, Lienard D; EORTC Melanoma Group. Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952): randomised controlled trial. Lancet. 2005 Oct 1;366(9492):1189-96. doi: 10.1016/S0140-6736(05)67482-X.

Reference Type RESULT
PMID: 16198768 (View on PubMed)

Other Identifiers

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EORTC-18952

Identifier Type: -

Identifier Source: secondary_id

CDR0000064718

Identifier Type: -

Identifier Source: org_study_id