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

NCT00002763 | Unknown Phase 3

• 2 other identifiers: CDR0000064718EORTC-18952
• Study Type: interventional
• Target: 1,000
• Locations: 19 countries
• Sites: 84

Brief Summary

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.

Conditions

Melanoma (Skin)

Keywords

stage III melanoma; recurrent melanoma

Interventions

recombinant interferon alfa BIOLOGICAL

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (86)

Krankenhaus der Elisabethinen

Linz, 4020, Austria

Location

Landeskrankenanstalten - Salzburg

Salzburg, 5020, Austria

Location

Hopital Universitaire Erasme

Brussels, 1070, Belgium

Location

Institut Jules Bordet

Brussels (Bruxelles), 1000, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels (Bruxelles), 1200, Belgium

Location

Centre Hospitalier Notre Dame - Reine Fabiola

Charleroi, 6000, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, B-2650, Belgium

Location

Universitair Ziekenhuis Gent

Ghent (Gent), B-9000, Belgium

Location

U.Z. Gasthuisberg

Leuven, B-3000, Belgium

Location

Alexander's University Hospital

Sofia, 1431, Bulgaria

Location

National Centre of Oncology

Sofia, 1756, Bulgaria

Location

University Hospital Sestre Milosrdnice

Zagreb, 10000, Croatia

Location

Estonian Cancer Center

Tallinn, 11619, Estonia

Location

Tampere University Hospital

Tampere, 33521, Finland

Location

Turku University Central Hospital

Turku, FIN-2-0521, Finland

Location

CHU de Bordeaux - Hopital Pellegrin

Bordeaux, 33076, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

CHU Ambroise Pare

Boulogne-Billancourt, F-92104, France

Location

CHRU de Caen

Caen, 14033, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hopital L'Archet - 2

Nice, F-06202, France

Location

Hopital Bichat-Claude Bernard

Paris, 75018, France

Location

Hopital Saint-Louis

Paris, 75475, France

Location

Hopital Cochin

Paris, 75674, France

Location

Hopital Haut Leveque

Pessac, 33604, France

Location

Centre Eugene Marquis

Rennes, 35062, France

Location

Centre Rene Huguenin

Saint-Cloud, 92210, France

Location

Centre Hospitalier Regional et Universitaire de Saint-Etienne

Saint-Priest-en-Jarez, 42277, France

Location

Hopitaux Universitaire de Strasbourg

Strasbourg, 67091, France

Location

Centre Hospitalier Regional Metz Thionville

Thionville, 57126, France

Location

Institut Claudius Regaud

Toulouse, 31052, France

Location

Centre Hospitalier Universitaire Bretonneau de Tours

Tours, 37044, France

Location

Institut Gustave Roussy

Villejuif, F-94805, France

Location

Universitaetsklinikum Benjamin Franklin

Berlin, D-12200, Germany

Location

Robert Roessle Klinik

Berlin, D-13122, Germany

Location

Universitaets-Augenklinik - Erlangen

Erlangen, D-91054, Germany

Location

Georg August Universitaet

Göttingen, D-37075, Germany

Location

Universitats-Krankenhaus Eppendorf

Hamburg, D-20246, Germany

Location

Haematologisch-Onkologische Praxis Altona

Hamburg, D-22765, Germany

Location

Department of Dematology, Hannover Medical School

Hanover, D-30449, Germany

Location

Universitaets-Hautklinik Heidelberg

Heidelberg, D-69115, Germany

Location

Universitatsklinik, Saarland

Homburg/Saar, D-66421, Germany

Location

III Medizinische Klinik Mannheim

Mannheim, D-68305, Germany

Location

Klinikum der Universitat Regensburg

Regensburg, DOH-9-3053, Germany

Location

Universitatshautklinik Eberhard - Karlsuniversitat Tubingen

Tübingen, DOH-7-2076, Germany

Location

Department of Dermatology

Ulm, DOH-8-9081, Germany

Location

Universitaet Wuerzburg/Hautkrankheiten

Würzburg, D-97080, Germany

Location

Wolfson Medical Center

Holon, 58100, Israel

Location

Tel-Aviv Medical Center-Ichilov Hospital

Tel Aviv, 62995, Israel

Location

Istituto Europeo Di Oncologia

Milan, 20141, Italy

Location

Academisch Ziekenhuis der Vrije Universiteit

Amsterdam, 1007 MB, Netherlands

Location

Antoni van Leeuwenhoekhuis

Amsterdam, 1066 CX, Netherlands

Location

Academisch Ziekenhuis Groningen

Groningen, 9713 EZ, Netherlands

Location

Leiden University Medical Center

Leiden, 2300 ZA, Netherlands

Location

University Medical Center Nijmegen

Nijmegen, NL-6252 HB, Netherlands

Location

Rotterdam Cancer Institute

Rotterdam, 3075 EA, Netherlands

Location

Academisch Ziekenhuis Utrecht

Utrecht, 3508 GA, Netherlands

Location

Medical University of Gdansk

Gdansk, 80-211, Poland

Location

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

Krakow (Cracow), 31-115, Poland

Location

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, 02-781, Poland

Location

Instituto Portugues de Oncologia de Francisco Gentil

Lisbon, 1093, Portugal

Location

Instituto Portugues de Oncologia do Porto

Porto, 4200, Portugal

Location

Russian Academy of Medical Sciences Cancer Research Center

Moscow, 115478, Russia

Location

Institute of Oncology and Radiology of Serbia

Belgrade, 11000, Serbia

Location

National Cancer Institute - Bratislava

Bratislava, 833 10, Slovakia

Location

Hospital Clinic y Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Clinico Universitario

Zaragoza, 50009, Spain

Location

Huddinge Hospital

Huddinge, S-141 86, Sweden

Location

Ospedale San Giovanni

Bellinzona, CH-6500, Switzerland

Location

Inselspital, Bern

Bern, CH-3010, Switzerland

Location

Ratisches Kantons und Regionalspital

Chur, CH-7000, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital - Saint Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Universitaetsspital

Zurich, CH-8091, Switzerland

Location

Cukurova University School of Medicine

Adana, 01330, Turkey (Türkiye)

Location

Vakif Gureba Training Hospital

Istanbul, 34296, Turkey (Türkiye)

Location

Istanbul University-Institute of Oncology

Istanbul, 34390, Turkey (Türkiye)

Location

Cerrahpasa Medical School

Istanbul, Turkey (Türkiye)

Location

Ege University Medical School

Izmir, 35220, Turkey (Türkiye)

Location

Bristol Oncology Centre

Bristol, England, BS2 8ED, United Kingdom

Location

Addenbrooke's NHS Trust

Cambridge, England, CB2 2QQ, United Kingdom

Location

St. James's Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Royal Marsden NHS Trust

London, England, SW3 6JJ, United Kingdom

Location

Derriford Hospital

Plymouth, England, PL6 8DH, United Kingdom

Location

Beatson Oncology Centre

Glasgow, Scotland, G11 6NT, United Kingdom

Location

Related Publications (8)

• 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.

  PMID: 22056637 BACKGROUND

• 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.

  PMID: 19509353 BACKGROUND

• 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.

  PMID: 12862495 BACKGROUND

• 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.

  PMID: 21546857 RESULT

• 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.

  PMID: 21087856 RESULT

• 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.

  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.

  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.

  PMID: 16198768 RESULT

MeSH Terms

Conditions

Melanoma

Interventions

Interferon-alpha

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Alexander M. M. Eggermont, MD, PhD

  Daniel Den Hoed Cancer Center at Erasmus Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: July 19, 2004
• Study Start: April 1, 1996
• Last Updated: November 16, 2011

Record last verified: 2011-11

Locations

FI (2); PL (3); AU (2); BE (7); ES (2); GB (6); SE (1); BU (2); TU (5); IT (1); NL (7); PT (2); FR (19); SL (1); CH (6); CR (1); RU (1); DE (14); IL (2)