Interferon Alfa Following Surgery in Treating Patients With Stage III Melanoma

NCT ID: NCT00006249

Last Updated: 2015-02-10

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

1258 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-06-30

Brief Summary

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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.

Detailed Description

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OBJECTIVES:

* Compare the effect of adjuvant therapy with pegylated interferon alfa vs observation, in terms of distant metastases-free survival, in patients with previously resected stage III melanoma.
* Compare the overall survival in these patients after treatment with pegylated interferon alfa vs observation.
* Determine the toxicity of pegylated interferon alfa in these patients.
* Determine the compliance of these patients treated with pegylated interferon alfa.
* Compare the quality of life in these patients after treatment with pegylated interferon alfa vs observation.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to type of nodal involvement (N1 vs N2), number of positive nodes (1 vs 2-4 vs 5 or more vs not assessed), Breslow primary (T1-2 vs T3 vs T4 vs unknown), ulceration of primary tumor (absent vs present vs unknown), sex, and center. Patients are randomized to one of two treatment arms.

* Arm I: Patients receive pegylated interferon alfa subcutaneously weekly for 5 years.
* Arm II: Patients undergo observation only. Treatment continues in the absence of distant metastases or unacceptable toxicity.

Quality of life is assessed at baseline, and then at months 3, 12, 24, 36, 48, and 60.

Patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 1,200 patients (600 per treatment arm) will be accrued for this study within 1.5-2 years.

Conditions

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Melanoma (Skin)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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observation

5 years observation + 5 years follow up

Group Type NO_INTERVENTION

No interventions assigned to this group

pegylated interferon alfa

5 years pegylated interferon alfa + 5 years follow up

Group Type EXPERIMENTAL

pegylated interferon alfa

Intervention Type BIOLOGICAL

adjuvant therapy

Intervention Type PROCEDURE

Interventions

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pegylated interferon alfa

Intervention Type BIOLOGICAL

adjuvant therapy

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 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

Responsible Party

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Responsibility Role SPONSOR

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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Peter MacCallum Cancer Institute

East Melbourne, Victoria, Australia

Site Status

Austin and Repatriation Medical Centre

Heidelberg West, Victoria, Australia

Site Status

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

Sir Charles Gairdner Hospital, Perth

Perth, Western Australia, Australia

Site Status

David Maddison Clincial Sciences

Newcastle, , Australia

Site Status

Institut Jules Bordet

Brussels, , Belgium

Site Status

Hopital Universitaire Erasme

Brussels, , Belgium

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Site Status

Clinique Notre Dame de Grace

Gosselies, , Belgium

Site Status

U.Z. Gasthuisberg

Leuven, , Belgium

Site Status

National Centre of Oncology

Sofia, , Bulgaria

Site Status

University Hospital Sestre Milosrdnice

Zagreb, , Croatia

Site Status

Charles University Hospital

Prague (Praha), , Czechia

Site Status

North-Estonian Regional Hospital Cancer Centre

Tallinn, , Estonia

Site Status

Centre Hospitalier Universitare d'Amens

Amiens, , France

Site Status

CHR de Besancon - Hopital Saint-Jacques

Besançon, , France

Site Status

Hopital Saint Andre

Bordeaux, , France

Site Status

CHU Ambroise Pare

Boulogne-Billancourt, , France

Site Status

CHR de Grenoble - La Tronche

Grenoble, , France

Site Status

Centre Hospitalier Regional et Universitaire de Lille

Lille, , France

Site Status

Centre Hospital Regional Universitaire de Limoges

Limoges, , France

Site Status

Centre Leon Berard

Lyon, , France

Site Status

Hopital St. Eloi

Montpellier, , France

Site Status

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

Montpellier, , France

Site Status

Hopital L'Archet - 2

Nice, , France

Site Status

Hopital Bichat - Claude Bernard

Paris, , France

Site Status

Hopital Saint-Louis

Paris, , France

Site Status

Hopital Haut Leveque

Pessac, , France

Site Status

Centre Hospitalier Universitaire

Reims, , France

Site Status

Centre Eugene Marquis

Rennes, , France

Site Status

Centre Rene Huguenin

Saint-Cloud, , France

Site Status

Centre Hospitalier Regional et Universitaire de Saint-Etienne

Saint-Priest-en-Jarez, , France

Site Status

Hopitaux Universitaire de Strasbourg

Strasbourg, , France

Site Status

Centre Hospitalier Regional Metz Thionville

Thionville, , France

Site Status

Centre Hospitalier Universitaire Bretonneau de Tours

Tours, , France

Site Status

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Robert Roessle Klinik

Berlin, , Germany

Site Status

Saint Josef Hospital

Bochum, , Germany

Site Status

Stadt. Kliniken

Dortmund, , Germany

Site Status

Universitaet Erlangen

Erlangen, , Germany

Site Status

Georg August Universitaet

Göttingen, , Germany

Site Status

Haematologisch-Onkologische Praxis Altona

Hamburg, , Germany

Site Status

Universitaets-Hautklinik Heidelberg

Heidelberg, , Germany

Site Status

Universitaet Leipzig - Chirurgische Klinik und Poliklinik I

Leipzig, , Germany

Site Status

Otto - Von - Guericke - Universitaet Magdeburg

Magdeburg, , Germany

Site Status

Klinikum der Stadt Mannheim

Mannheim, , Germany

Site Status

Universitaet Wuerzburg/Hautkrankheiten

Würzburg, , Germany

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

Wolfson Medical Center

Holon, , Israel

Site Status

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Centro di Riferimento Oncologico - Aviano

Aviano, , Italy

Site Status

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

Florence, , Italy

Site Status

Istituto Nazionale per la Ricerca sul Cancro

Genoa (Genova), , Italy

Site Status

European Institute of Oncology - Chemo Prevention

Milan, , Italy

Site Status

Istituto Nazionale per lo Studio e la Cura dei Tumori

Milano (Milan), , Italy

Site Status

Istituto Nazionale per lo Studio e la Cura dei Tumori

Naples, , Italy

Site Status

Istituto Regina Elena

Rome, , Italy

Site Status

Universita Degli Studi di Torino

Torino, , Italy

Site Status

Vrije Universiteit Medisch Centrum

Amsterdam, , Netherlands

Site Status

Leiden University Medical Center

Leiden, , Netherlands

Site Status

University Medical Center Nijmegen

Nijmegen, , Netherlands

Site Status

Erasmus University Medical Center

Rotterdam, , Netherlands

Site Status

Academisch Ziekenhuis Utrecht

Utrecht, , Netherlands

Site Status

Great Poland Cancer Center

Poznan, , Poland

Site Status

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, , Poland

Site Status

Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa

Lisbon, , Portugal

Site Status

Instituto Portugues de Oncologia Centro do Porto, SA

Porto, , Portugal

Site Status

Institute of Oncology, Ljubljana

Ljubljana, , Slovenia

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Clinico Universitario

Zaragoza, , Spain

Site Status

Kantonspital Aarau

Aarau, , Switzerland

Site Status

Inselspital, Bern

Bern, , Switzerland

Site Status

Ratisches Kantons und Regionalspital

Chur, , Switzerland

Site Status

UniversitaetsSpital

Zurich, , Switzerland

Site Status

Vakif Gureba Training Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Ege University Medical School

Izmir, , Turkey (Türkiye)

Site Status

Bristol Haematology and Oncology Centre

Bristol, England, United Kingdom

Site Status

Addenbrooke's NHS Trust

Cambridge, England, United Kingdom

Site Status

Cheltenham General Hospital

Cheltenham, England, United Kingdom

Site Status

Royal Devon and Exeter Hospital

Exeter, England, United Kingdom

Site Status

Royal Surrey County Hospital

Guildford, England, United Kingdom

Site Status

Princess Royal Hospital

Hull, England, United Kingdom

Site Status

St. James's Hospital

Leeds, England, United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, England, United Kingdom

Site Status

Saint Bartholomew's Hospital

London, England, United Kingdom

Site Status

Royal Free Hospital

London, England, United Kingdom

Site Status

Guy's and St. Thomas' Hospitals NHS Trust

London, England, United Kingdom

Site Status

St. George's Hospital

London, England, United Kingdom

Site Status

Royal Marsden NHS Trust

London, England, United Kingdom

Site Status

Clatterbridge Centre for Oncology NHS Trust

Merseyside, England, United Kingdom

Site Status

Newcastle General Hospital

Newcastle upon Tyne, England, United Kingdom

Site Status

Salisbury District Hospital

Salisbury, England, United Kingdom

Site Status

Weston Park Hospital

Sheffield, England, United Kingdom

Site Status

Southampton General Hospital

Southampton, England, United Kingdom

Site Status

Royal Marsden Hospital

Sutton, England, United Kingdom

Site Status

Southend NHS Trust Hospital

Westcliff-on-Sea, England, United Kingdom

Site Status

Belfast City Hospital Trust

Belfast, Northern Ireland, United Kingdom

Site Status

Ninewells Hospital and Medical School

Dundee, Scotland, United Kingdom

Site Status

Western Infirmary

Glasgow, Scotland, United Kingdom

Site Status

Velindre Cancer Center at Velinde Hospital

Cardiff, Wales, United Kingdom

Site Status

Selly Oak Hospital at University Hospital NHS Trust

Birmingham, , United Kingdom

Site Status

Churchill Hospital

Oxford, , United Kingdom

Site Status

Countries

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Australia Belgium Bulgaria Croatia Czechia Estonia France Germany Israel Italy Netherlands Poland Portugal Slovenia Spain 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)

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.

Reference Type 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.

Reference Type RESULT
PMID: 20385998 (View on PubMed)

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.

Reference Type RESULT
PMID: 19621225 (View on PubMed)

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.

Reference Type RESULT
PMID: 19433686 (View on PubMed)

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.

Reference Type RESULT
PMID: 19793643 (View on PubMed)

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.

Reference Type RESULT
PMID: 18620949 (View on PubMed)

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.

Reference Type RESULT

Other Identifiers

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EORTC-18991

Identifier Type: -

Identifier Source: secondary_id

EORTC-18991

Identifier Type: -

Identifier Source: org_study_id

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