Interferon Alfa Following Surgery in Treating Patients With Stage III Melanoma

NCT00006249 | Unknown Phase 3

• 1 other identifier: EORTC-18991
• Study Type: interventional
• Target: 1,258
• Locations: 17 countries
• Sites: 103

Brief Summary

RATIONALE: Interferon alfa may interfere with the growth of the cancer cells. It is not yet known if this treatment is more effective than observation following surgery for stage III melanoma. PURPOSE: Randomized phase III trial to determine the effectiveness of interferon alfa in treating patients who have undergone surgery for stage III melanoma.

Conditions

Melanoma (Skin)

Keywords

stage III melanoma

Outcome Measures

Primary Outcomes (1)

• distant-metastasis free-survival (DMFS)

  distant-metastasis free-survival (DMFS) after randomization

  from randomization

Secondary Outcomes (2)

• survival

  from randomization till death

• toxicity

  from randomization

Other Outcomes (1)

• quality of life

  from randomization

Study Arms (2)

observation

NO INTERVENTION

5 years observation + 5 years follow up

pegylated interferon alfa

EXPERIMENTAL

5 years pegylated interferon alfa + 5 years follow up

Biological: pegylated interferon alfa; Procedure: adjuvant therapy

Interventions

pegylated interferon alfa BIOLOGICAL

pegylated interferon alfa

adjuvant therapy PROCEDURE

pegylated interferon alfa

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed previously resected stage III primary cutaneous melanoma or unknown primary with regional lymph node involvement * N1 disease * Microscopic, nonpalpable nodal involvement * Primary melanoma of any stage with clinically inapparent N1 regional lymph node metastases (T1-4, N1, M0) detected by elective lymph node dissection or sentinel node biopsy * N2 disease * Palpable nodal involvement with synchronous primary melanoma or apparent nodal disease after prior excision (any pT, N2, M0) * Regional lymph node recurrence at any interval after surgery for primary melanoma of any depth (T1-4, rN2, M0) * Complete resection of primary melanoma with adequate surgical margins * Full lymphadenectomy must be performed within 70 days of study * No mucous membrane melanoma or ocular melanoma * No evidence of distant or nonregional lymph node metastases or in transit metastases (even if previously resected) * No incompletely resected disease due to gross extracapsular extension PATIENT CHARACTERISTICS: Age: * 18 to 70 Performance status: * ECOG 0-1 Life expectancy: * Not specified Hematopoietic: * WBC at least 3,000/mm\^3 * Platelet count greater than 100,000/mm\^3 * Hemoglobin at least 9 g/dL Hepatic: * SGOT and SGPT less than 2 times upper limit of normal * No active hepatitis Renal: * Creatinine less than 2.0 mg/dL Cardiovascular: * No severe cardiovascular disease including the following: * Arrhythmias requiring chronic treatment * Congestive heart failure (New York Heart Association class III or IV) * Symptomatic ischemic heart disease Other: * No other prior malignancy within the past 5 years except surgically cured nonmelanomatous skin cancer or carcinoma in situ of the cervix * No thyroid dysfunction unresponsive to therapy * No uncontrolled diabetes mellitus * No active autoimmune disease * No active and/or uncontrolled infection * No history of neuropsychiatric disorder requiring hospitalization * No known active alcohol or drug abuse * HIV negative * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * No prior interferon alfa * No prior immunotherapy for melanoma * No other concurrent immunologic or biologic therapy * No concurrent colony stimulating factors including epoetin alfa and filgrastim (G-CSF) Chemotherapy: * No prior chemotherapy for melanoma * No concurrent chemotherapy Endocrine therapy: * No prior hormonal therapy for melanoma * No concurrent hormonal therapy * No concurrent chronic systemic corticosteroid therapy Radiotherapy: * No prior radiotherapy for melanoma * No concurrent radiotherapy Surgery: * See Disease Characteristics * Recovered from any prior recent surgery Other: * At least 30 days since other prior experimental therapy * No other concurrent investigational drugs

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 (104)

Peter MacCallum Cancer Institute

East Melbourne, Victoria, 8006, Australia

Location

Austin and Repatriation Medical Centre

Heidelberg West, Victoria, 3081, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Sir Charles Gairdner Hospital, Perth

Perth, Western Australia, 6009, Australia

Location

David Maddison Clincial Sciences

Newcastle, NSW 2300, Australia

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Hopital Universitaire Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, B-2650, Belgium

Location

Clinique Notre Dame de Grace

Gosselies, 6041, Belgium

Location

U.Z. Gasthuisberg

Leuven, B-3000, Belgium

Location

National Centre of Oncology

Sofia, 1756, Bulgaria

Location

University Hospital Sestre Milosrdnice

Zagreb, 10000, Croatia

Location

Charles University Hospital

Prague (Praha), 128 08, Czechia

Location

North-Estonian Regional Hospital Cancer Centre

Tallinn, 11619, Estonia

Location

Centre Hospitalier Universitare d'Amens

Amiens, 80054, France

Location

CHR de Besancon - Hopital Saint-Jacques

Besançon, 25030, France

Location

Hopital Saint Andre

Bordeaux, 33075, France

Location

CHU Ambroise Pare

Boulogne-Billancourt, F-92104, France

Location

CHR de Grenoble - La Tronche

Grenoble, 38043, France

Location

Centre Hospitalier Regional et Universitaire de Lille

Lille, 59037, France

Location

Centre Hospital Regional Universitaire de Limoges

Limoges, 87042, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Hopital St. Eloi

Montpellier, 34295, France

Location

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, 34298, 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 Haut Leveque

Pessac, 33604, France

Location

Centre Hospitalier Universitaire

Reims, 51092, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Centre Rene Huguenin

Saint-Cloud, 92211, 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

Centre Hospitalier Universitaire Bretonneau de Tours

Tours, 37044, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy

Villejuif, F-94805, France

Location

Robert Roessle Klinik

Berlin, D-13122, Germany

Location

Saint Josef Hospital

Bochum, D-44791, Germany

Location

Stadt. Kliniken

Dortmund, 44123, Germany

Location

Universitaet Erlangen

Erlangen, D-91054, Germany

Location

Georg August Universitaet

Göttingen, D-37075, Germany

Location

Haematologisch-Onkologische Praxis Altona

Hamburg, D-22765, Germany

Location

Universitaets-Hautklinik Heidelberg

Heidelberg, D-69115, Germany

Location

Universitaet Leipzig - Chirurgische Klinik und Poliklinik I

Leipzig, D-04103, Germany

Location

Otto - Von - Guericke - Universitaet Magdeburg

Magdeburg, D-39120, Germany

Location

Klinikum der Stadt Mannheim

Mannheim, D-68135, Germany

Location

Universitaet Wuerzburg/Hautkrankheiten

Würzburg, D-97080, Germany

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Wolfson Medical Center

Holon, 58100, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Centro di Riferimento Oncologico - Aviano

Aviano, 33081, Italy

Location

Ospendale S.M. Annunziata-A.S.DI Firenze

Florence, I-50011, Italy

Location

Istituto Nazionale per la Ricerca sul Cancro

Genoa (Genova), 16132, Italy

Location

European Institute of Oncology - Chemo Prevention

Milan, 20141, Italy

Location

Istituto Nazionale per lo Studio e la Cura dei Tumori

Milano (Milan), 20133, Italy

Location

Istituto Nazionale per lo Studio e la Cura dei Tumori

Naples, 80131, Italy

Location

Istituto Regina Elena

Rome, 00161, Italy

Location

Universita Degli Studi di Torino

Torino, 10126, Italy

Location

Vrije Universiteit Medisch Centrum

Amsterdam, 1007 MB, Netherlands

Location

Leiden University Medical Center

Leiden, 2300 CA, Netherlands

Location

University Medical Center Nijmegen

Nijmegen, NL-6500 HB, Netherlands

Location

Erasmus University Medical Center

Rotterdam, 3075 EA, Netherlands

Location

Academisch Ziekenhuis Utrecht

Utrecht, 3584 CX, Netherlands

Location

Great Poland Cancer Center

Poznan, 61 866, Poland

Location

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, 02-781, Poland

Location

Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa

Lisbon, 1099-023 Codex, Portugal

Location

Instituto Portugues de Oncologia Centro do Porto, SA

Porto, 4200, Portugal

Location

Institute of Oncology, Ljubljana

Ljubljana, Sl-1000, Slovenia

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Clinico Universitario

Zaragoza, 50009, Spain

Location

Kantonspital Aarau

Aarau, 5001, Switzerland

Location

Inselspital, Bern

Bern, CH-3010, Switzerland

Location

Ratisches Kantons und Regionalspital

Chur, CH-7000, Switzerland

Location

UniversitaetsSpital

Zurich, CH-8091, Switzerland

Location

Vakif Gureba Training Hospital

Istanbul, 34296, Turkey (Türkiye)

Location

Ege University Medical School

Izmir, 35220, Turkey (Türkiye)

Location

Bristol Haematology and Oncology Centre

Bristol, England, BS2 8ED, United Kingdom

Location

Addenbrooke's NHS Trust

Cambridge, England, CB2 2QQ, United Kingdom

Location

Cheltenham General Hospital

Cheltenham, England, GL53 7AN, United Kingdom

Location

Royal Devon and Exeter Hospital

Exeter, England, EX2 5DW, United Kingdom

Location

Royal Surrey County Hospital

Guildford, England, GU2 5XX, United Kingdom

Location

Princess Royal Hospital

Hull, England, HU8 9HE, United Kingdom

Location

St. James's Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Leicester Royal Infirmary

Leicester, England, LE1 5WW, United Kingdom

Location

Saint Bartholomew's Hospital

London, England, EC1A 7BE, United Kingdom

Location

Royal Free Hospital

London, England, NW3 2QG, United Kingdom

Location

Guy's and St. Thomas' Hospitals NHS Trust

London, England, SE1 9RT, United Kingdom

Location

St. George's Hospital

London, England, SW17 0QT, United Kingdom

Location

Royal Marsden NHS Trust

London, England, SW3 6JJ, United Kingdom

Location

Clatterbridge Centre for Oncology NHS Trust

Merseyside, England, CH63 4JY, United Kingdom

Location

Newcastle General Hospital

Newcastle upon Tyne, England, NE4 6BE, United Kingdom

Location

Salisbury District Hospital

Salisbury, England, SP2 8BJ, United Kingdom

Location

Weston Park Hospital

Sheffield, England, S1O 2SJ, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Royal Marsden Hospital

Sutton, England, SM2 5PT, United Kingdom

Location

Southend NHS Trust Hospital

Westcliff-on-Sea, England, SS0 0RY, United Kingdom

Location

Belfast City Hospital Trust

Belfast, Northern Ireland, BT9 7AB, United Kingdom

Location

Ninewells Hospital and Medical School

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Western Infirmary

Glasgow, Scotland, G11 6NT, United Kingdom

Location

Velindre Cancer Center at Velinde Hospital

Cardiff, Wales, CF4 7XL, United Kingdom

Location

Selly Oak Hospital at University Hospital NHS Trust

Birmingham, B29 6JD, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LJ, 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

• Eggermont AM, Suciu S, Santinami M, et al.: EORTC 18991 phase III trial: Long-term adjuvant pegylated interferon-α2b (PEG-IFN) versus observation in resected stage III melanoma: long-term results at 7.6-years follow-up. [Abstract] J Clin Oncol 29 (Suppl 15): A-8506b, 2011.

  RESULT

• Bouwhuis MG, Suciu S, Testori A, Kruit WH, Sales F, Patel P, Punt CJ, Santinami M, Spatz A, Ten Hagen TL, Eggermont AM. Phase III trial comparing adjuvant treatment with pegylated interferon Alfa-2b versus observation: prognostic significance of autoantibodies--EORTC 18991. J Clin Oncol. 2010 May 10;28(14):2460-6. doi: 10.1200/JCO.2009.24.6264. Epub 2010 Apr 12.

  PMID: 20385998 RESULT

• Eggermont AM, Bouwhuis MG, Kruit WH, Testori A, ten Hagen T, Yver A, Xu C. Serum concentrations of pegylated interferon alpha-2b in patients with resected stage III melanoma receiving adjuvant pegylated interferon alpha-2b in a randomized phase III trial (EORTC 18991). Cancer Chemother Pharmacol. 2010 Mar;65(4):671-7. doi: 10.1007/s00280-009-1072-z. Epub 2009 Jul 21.

  PMID: 19621225 RESULT

• Bottomley A, Coens C, Suciu S, Santinami M, Kruit W, Testori A, Marsden J, Punt C, Sales F, Gore M, Mackie R, Kusic Z, Dummer R, Patel P, Schadendorf D, Spatz A, Keilholz U, Eggermont A. Adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma: a phase III randomized controlled trial of health-related quality of life and symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group. J Clin Oncol. 2009 Jun 20;27(18):2916-23. doi: 10.1200/JCO.2008.20.2069. Epub 2009 May 11.

  PMID: 19433686 RESULT

• Fusi A, Collette S, Busse A, Suciu S, Rietz A, Santinami M, Kruit WH, Testori A, Punt CJ, Dalgleish AG, Spatz A, Eggermont AM, Keilholz U. Circulating melanoma cells and distant metastasis-free survival in stage III melanoma patients with or without adjuvant interferon treatment (EORTC 18991 side study). Eur J Cancer. 2009 Dec;45(18):3189-97. doi: 10.1016/j.ejca.2009.09.004. Epub 2009 Sep 28.

  PMID: 19793643 RESULT

• Eggermont AM, Suciu S, Santinami M, Testori A, Kruit WH, Marsden J, Punt CJ, Sales F, Gore M, MacKie R, Kusic Z, Dummer R, Hauschild A, Musat E, Spatz A, Keilholz U; EORTC Melanoma Group. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet. 2008 Jul 12;372(9633):117-126. doi: 10.1016/S0140-6736(08)61033-8.

  PMID: 18620949 RESULT

• Eggermont AM, Suciu S, Santinami M, et al.: EORTC 18991: long-term adjuvant pegylated interferon-alpha2b (PEG-IFN) compared to observation in resected stage III melanoma, final results of a randomized phase III trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-8504, 473s, 2007.

  RESULT

MeSH Terms

Conditions

Melanoma

Interventions

Chemotherapy, Adjuvant

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)

Combined Modality Therapy; Therapeutics; Drug Therapy

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
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2000
• First Posted: January 27, 2003
• Study Start: June 1, 2000
• Primary Completion: August 1, 2003
• Last Updated: February 10, 2015

Record last verified: 2015-02

Locations

ES (2); CZ (1); IL (3); IT (8); TU (2); PT (2); CR (1); CH (4); PL (2); BE (6); GB (26); NL (5); AU (5); FR (23); BU (1); SL (1); DE (11)