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.

Condition	Treatment or Intervention	Phase
stage III melanoma	Drug: pegylated interferon alfa  Procedure: biological response modifier therapy  Procedure: cytokine therapy  Procedure: interferon therapy	Phase III

Further Study Details: 

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.

Ages Eligible for Study:  18 Years   -   70 Years,  Genders Eligible for Study:  Both

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

Australia
      David Maddison Clincial Sciences, Newcastle,  NSW 2300,  Australia
Australia, Victoria
      Austin and Repatriation Medical Centre, Heidelberg West,  Victoria,  3081,  Australia
      Peter MacCallum Cancer Institute, East Melbourne,  Victoria,  8006,  Australia
Australia, Western Australia
      Royal Perth Hospital, Perth,  Western Australia,  6000,  Australia
      Sir Charles Gairdner Hospital, Perth, Perth,  Western Australia,  6009,  Australia
Belgium
      Clinique Notre Dame de Grace, Gosselies,  6041,  Belgium
      Cliniques Universitaires Saint-Luc, Brussels,  1200,  Belgium
      Hopital Universitaire Erasme, Brussels,  1070,  Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
Bulgaria
      National Centre of Oncology, Sofia,  1756,  Bulgaria
Croatia
      University Hospital Sestre Milosrdnice, Zagreb,  10000,  Croatia
Czech Republic
      Charles University Hospital, Prague (Praha),  128 08,  Czech Republic
Estonia
      North-Estonian Regional Hospital Cancer Centre, Tallinn,  11619,  Estonia
France
      Centre Alexis Vautrin, Vandoeuvre-les-Nancy,  54511,  France
      Centre Eugene Marquis, Rennes,  35042,  France
      Centre Hospital Regional Universitaire de Limoges, Limoges,  87042,  France
      Centre Hospitalier Regional et Universitaire de Lille, Lille,  59037,  France
      Centre Hospitalier Regional et Universitaire de Saint-Etienne, Saint-Priest-en-Jarez,  42277,  France
      Centre Hospitalier Regional Metz Thionville, Thionville,  57126,  France
      Centre Hospitalier Universitaire Bretonneau de Tours, Tours,  37044,  France
      Centre Hospitalier Universitaire, Reims,  51092,  France
      Centre Hospitalier Universitare d'Amens, Amiens,  80054,  France
      Centre Leon Berard, Lyon,  69373,  France
      Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle, Montpellier,  34298,  France
      Centre Rene Huguenin, Saint Cloud,  92211,  France
      CHR de Besancon - Hopital Saint-Jacques, Besancon,  25030,  France
      CHR de Grenoble - La Tronche, Grenoble,  38043,  France
      CHU Ambroise Pare, Boulogne-Billancourt,  F-92104,  France
      Hopital Bichat - Claude Bernard, Paris,  75018,  France
      Hopital Haut Leveque, Pessac,  33604,  France
      Hopital L'Archet - 2, Nice,  F-06202,  France
      Hopital Saint Andre, Bordeaux,  33075,  France
      Hopital Saint-Louis, Paris,  75475,  France
      Hopital St. Eloi, Montpellier,  34295,  France
      Hopitaux Universitaire de Strasbourg, Strasbourg,  67091,  France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
Germany
      Georg August Universitaet, Goettingen,  D-37075,  Germany
      Haematologisch-Onkologische Praxis Altona, Hamburg,  D-22765,  Germany
      Klinikum der Stadt Mannheim, Mannheim,  D-68135,  Germany
      Otto - Von - Guericke - Universitaet Magdeburg, Magdeburg,  D-39120,  Germany
      Robert Roessle Klinik, Berlin,  D-13122,  Germany
      Saint Josef Hospital, Bochum 1,  D-44791,  Germany
      Stadt. Kliniken, Dortmund,  44123,  Germany
      Universitaet Erlangen, Erlangen,  D-91054,  Germany
      Universitaet Leipzig - Chirurgische Klinik und Poliklinik I, Leipzig,  D-04103,  Germany
      Universitaet Wuerzburg/Hautkrankheiten, Wuerzburg,  D-97080,  Germany
      Universitaets-Hautklinik Heidelberg, Heidelberg,  D-69115,  Germany
Israel
      Rambam Medical Center, Haifa,  31096,  Israel
      Tel-Aviv Sourasky Medical Center, Tel Aviv,  64239,  Israel
      Wolfson Medical Center, Holon,  58100,  Israel
Italy
      Centro di Riferimento Oncologico - Aviano, Aviano,  33081,  Italy
      European Institute of Oncology - Chemo Prevention, Milano,  20141,  Italy
      Istituto Nazionale per la Ricerca sul Cancro, Genoa (Genova),  16132,  Italy
      Istituto Nazionale per lo Studio e la Cura dei Tumori, Naples,  80131,  Italy
      Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano (Milan),  20133,  Italy
      Istituto Regina Elena, Rome,  00161,  Italy
      Ospendale S.M. Annunziata-A.S.DI Firenze, Firenze,  I-50011,  Italy
      Universita Degli Studi di Torino, Torino,  10126,  Italy
Netherlands
      Academisch Ziekenhuis Utrecht, Utrecht,  3584 CX,  Netherlands
      Erasmus University Medical Center, Rotterdam,  3075 EA,  Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands
      Vrije Universiteit Medisch Centrum, Amsterdam,  1007 MB,  Netherlands
Poland
      Great Poland Cancer Center, Poznan,  61 866,  Poland
      Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw,  02-781,  Poland
Portugal
      Instituto Portugues de Oncologia Centro do Porto, SA, Porto,  4200,  Portugal
      Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa, Lisbon,  1099-023 Codex,  Portugal
Slovenia
      Institute of Oncology, Ljubljana, LJUBLJANA,  Sl-1000,  Slovenia
Spain
      Hospital Clinico Universitario, Zaragoza,  50009,  Spain
      Hospital Universitario 12 de Octubre, Madrid,  28041,  Spain
Switzerland
      Inselspital, Bern, Bern,  CH-3010,  Switzerland
      Kantonspital Aarau, AARAU,  5001,  Switzerland
      Ratisches Kantons und Regionalspital, Chur,  CH-7000,  Switzerland
      UniversitaetsSpital, Zurich,  CH-8091,  Switzerland
Turkey
      Ege University Medical School, Izmir,  35220,  Turkey
      Vakif Gureba Training Hospital, Istanbul,  34296,  Turkey
United Kingdom
      Churchill Hospital, Oxford,  OX3 7LJ,  United Kingdom
      Selly Oak Hospital at University Hospital NHS Trust, Birmingham,  B29 6JD,  United Kingdom
United Kingdom, England
      Addenbrooke's NHS Trust, Cambridge,  England,  CB2 2QQ,  United Kingdom
      Bristol Haematology and Oncology Centre, Bristol,  England,  BS2 8ED,  United Kingdom
      Cheltenham General Hospital, Cheltenham,  England,  GL53 7AN,  United Kingdom
      Clatterbridge Centre for Oncology NHS Trust, MERSEYSIDE,  England,  CH63 4JY,  United Kingdom
      Guy's and St. Thomas' Hospitals NHS Trust, London,  England,  SE1 9RT,  United Kingdom
      Leicester Royal Infirmary, Leicester,  England,  LE1 5WW,  United Kingdom
      Newcastle General Hospital, Newcastle upon Tyne,  England,  NE4 6BE,  United Kingdom
      Princess Royal Hospital, Hull,  England,  HU8 9HE,  United Kingdom
      Royal Devon and Exeter Hospital, Exeter,  England,  EX2 5DW,  United Kingdom
      Royal Free Hospital, London,  England,  NW3 2QG,  United Kingdom
      Royal Marsden Hospital, Sutton,  England,  SM2 5PT,  United Kingdom
      Royal Marsden NHS Trust, London,  England,  SW3 6JJ,  United Kingdom
      Royal Surrey County Hospital, Guildford,  England,  GU2 5XX,  United Kingdom
      Saint Bartholomew's Hospital, London,  England,  EC1A 7BE,  United Kingdom
      Salisbury District Hospital, Salisbury,  England,  SP2 8BJ,  United Kingdom
      Southampton General Hospital, Southampton,  England,  SO16 6YD,  United Kingdom
      Southend NHS Trust Hospital, Westcliff-On-Sea,  England,  SS0 0RY,  United Kingdom
      St. George's Hospital, London,  England,  SW17 0QT,  United Kingdom
      St. James's Hospital, Leeds,  England,  LS9 7TF,  United Kingdom
      Weston Park Hospital, Sheffield,  England,  S1O 2SJ,  United Kingdom
United Kingdom, Northern Ireland
      Belfast City Hospital Trust, Belfast,  Northern Ireland,  BT9 7AB,  United Kingdom
United Kingdom, Scotland
      Ninewells Hospital and Medical School, Dundee,  Scotland,  DD1 9SY,  United Kingdom
      Western Infirmary, Glasgow,  Scotland,  G11 6NT,  United Kingdom
United Kingdom, Wales
      Velindre Cancer Center at Velinde Hospital, Cardiff,  Wales,  CF4 7XL,  United Kingdom

Study chairs or principal investigators

Alexander M.M. Eggermont, MD,  Erasmus University Medical Center   

Study ID Numbers:  CDR0000068181; EORTC-18991
Record last reviewed:  October 2003
Last Updated:  October 13, 2004
Record first received:  September 11, 2000
ClinicalTrials.gov Identifier:  NCT00006249
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08