RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. It is not yet known whether vaccine therapy is more effective than observation alone for melanoma.

PURPOSE: This randomized phase III trial is studying vaccine therapy to see how well it works compared to observation alone in treating patients with primary stage II melanoma.

Condition	Treatment or Intervention	Phase
stage II melanoma	Drug: GM2-KLH vaccine  Drug: QS21  Procedure: adjuvant therapy  Procedure: biological response modifier therapy  Procedure: non-specific immune-modulator therapy  Procedure: non-tumor cell derivative vaccine  Procedure: vaccine therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the effect of immunization with GM2-KLH and QS21 to observation on the disease-free survival of patients with primary cutaneous stage II melanoma after adequate surgery.
• Determine overall survival and toxicity in the two treatment arms.

OUTLINE: This is a randomized, open-label, parallel, multicenter study. Patients are stratified according to participating center, tumor thickness (greater than 1.5 to 3.0 mm vs greater than 3.0 to 4.0 mm vs greater than 4.0 mm), gender, ulceration (yes vs no), and presence of additional staging procedures of regional lymph nodes (yes vs no). Patients are randomized to one of two arms.

• Arm I: Patients are vaccinated with GM2-KLH and QS21 subcutaneously on day 1 of weeks 1-4, 12, 24, 36, 48, 60, 72, 84, 96, 120, and 144 for a total of 14 vaccinations.
• Arm II: Patients undergo observation. Patients are followed every 6 months for 7 years.

PROJECTED ACCRUAL: A total of 1300 patients (650 per arm) will be accrued for this study within 36 months.

Ages Eligible for Study:  18 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary stage II melanoma greater than 1.5 mm without evidence of lymph node metastases
• T3 or T4, N0, M0
• Must originate in the skin
• Wide excision with a minimum of 1-2 cm margin surrounding primary lesion or biopsy scar
• No more than 56 days since definitive surgical treatment (wide excision)
• No more than 12 weeks since primary surgery
• No clinical, radiological, or pathological evidence of incompletely resected disease, lymph node metastases, in-transit metastasis, or any distant metastatic disease

PATIENT CHARACTERISTICS: Age:

• 18 to 80

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.8 g/dL

Hepatic:

• SGOT/SGPT no greater than 2 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2 times ULN
• LDH no greater than 2 times ULN
• Bilirubin no greater than 2 times ULN
• Hepatitis B and C negative

Renal:

• Creatinine normal

Other:

• Not pregnant or nursing
• Negative pregnancy test
• No prior or other concurrent cancer except carcinoma in situ of the cervix or basal or squamous cell skin cancer
• No autoimmune disorders
• No conditions requiring systemic treatment with immunosuppressive drugs including treatment with systemic corticosteroids
• No history of CNS demyelinating or inflammatory disease
• No hereditary or acquired peripheral neuropathy
• No other significant medical or surgical condition or psychiatric disorders requiring medication that would preclude study
• No history of severe allergic reaction to shellfish
• HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior immunotherapy
• No other concurrent biologic therapy

Chemotherapy:

• No prior systemic chemotherapy
• No concurrent cytotoxic chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except replacement therapy
• No concurrent corticosteroids
• No concurrent chronic systemic steroids

Radiotherapy:

• No prior adjuvant radiotherapy
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No prior preoperative infusion or perfusion therapy
• No concurrent immunosuppressive medications
• No other concurrent anticancer therapy

Australia, Western Australia
      Royal Perth Hospital, Perth,  Western Australia,  6000,  Australia; Recruiting
Belgium
      Cliniques Universitaires Saint-Luc, Brussels,  1200,  Belgium; Recruiting
      Hopital de Jolimont, Haine-Saint-Paul,  7100,  Belgium; Recruiting
      Hopital Universitaire Erasme, Brussels,  1070,  Belgium; Recruiting
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium; Recruiting
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium; Recruiting
      Universitair Ziekenhuis Gent, Ghent,  B-9000,  Belgium; Recruiting
Denmark
      Aarhus University Hospital - Aarhus Sygehus - Norrebrogade, Aarhus,  DK-8000,  Denmark; Recruiting
      Herlev Hospital - University Hospital of Copenhagen, Copenhagen,  DK-2730,  Denmark; Recruiting
      Odense University Hospital, Odense,  DK-5000,  Denmark; Recruiting
      Rigshospitalet, Copenhagen,  2100,  Denmark; Recruiting
Estonia
      North-Estonian Regional Hospital Surgical Oncology Centre, Tallinn,  11619,  Estonia; Recruiting
Finland
      Tampere University Hospital, Tampere,  33521,  Finland; Recruiting
France
      Centre Alexis Vautrin, Vandoeuvre-les-Nancy,  54511,  France; Recruiting
      Centre Eugene Marquis, Rennes,  35042,  France; Recruiting
      Centre Hospitalier Regional et Universitaire de Lille, Lille,  59037,  France; Recruiting
      Centre Hospitalier Regional Metz Thionville, Thionville,  57126,  France; Recruiting
      Centre Jean Perrin, Clermont-Ferrand,  63011,  France; Recruiting
      Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle, Montpellier,  34298,  France; Recruiting
      CHR de Besancon - Hopital Saint-Jacques, Besancon,  25030,  France; Recruiting
      CHU Ambroise Pare, Boulogne-Billancourt,  F-92104,  France; Recruiting
      CHU de Caen, Caen,  14033,  France; Recruiting
      Hopital Bichat - Claude Bernard, Paris,  75018,  France; Recruiting
      Hopital L'Archet - 2, Nice,  F-06202,  France; Recruiting
      Hopital Saint-Louis, Paris,  75475,  France; Recruiting
      Hopital St. Eloi, Montpellier,  34295,  France; Recruiting
      Institut Gustave Roussy, Villejuif,  F-94805,  France; Recruiting
Germany
      Haematologisch-Onkologische Praxis Altona, Hamburg,  D-22765,  Germany; Recruiting
      Universitaets-Hautklinik Wuerzburg, Wuerzburg,  D-97080,  Germany; Recruiting
Israel
      Rambam Medical Center, Haifa,  31096,  Israel; Recruiting
      Wolfson Medical Center, Holon,  58100,  Israel; Recruiting
Italy
      Centro di Riferimento Oncologico - Aviano, Aviano,  33081,  Italy; Recruiting
      European Institute of Oncology, Milano,  20141,  Italy; Recruiting
      Istituto Nazionale per la Ricerca sul Cancro, Genoa (Genova),  16132,  Italy; Recruiting
      Istituto Nazionale per lo Studio e la Cura dei Tumori, Naples,  80131,  Italy; Recruiting
      Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano (Milan),  20133,  Italy; Recruiting
      Istituto Regina Elena, Rome,  00161,  Italy; Recruiting
      Ospedale S. Camillo-Forlanini, Rome,  00152,  Italy; Recruiting
      Ospendale S.M. Annunziata-A.S.DI Florence, Firenze,  I-50011,  Italy; Recruiting
      Universita Degli Studi di Turin, Torino,  10126,  Italy; Recruiting
      Universita di Padova, Padova,  35128,  Italy; Recruiting
Netherlands
      Daniel Den Hoed Cancer Center at Erasmus Medical Center, Rotterdam,  3008 AE,  Netherlands; Recruiting
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands; Recruiting
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands; Recruiting
Norway
      Norwegian Radium Hospital, Oslo,  N-0310,  Norway; Recruiting
Poland
      Great Poland Cancer Center, Poznan,  61 866,  Poland; Recruiting
      Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw,  02-781,  Poland; Recruiting
Portugal
      Hospital Distrital De Santarem, Santarem,  2000,  Portugal; Recruiting
      Instituto Portugues de Oncologia Centro do Porto, SA, Porto,  4200,  Portugal; Recruiting
Russian Federation
      Russian Academy of Medical Sciences Cancer Research Center, Moscow,  115478,  Russian Federation; Recruiting
Spain
      Hospital Clinico Universitario Lozano Blesa, Zaragoza,  50009,  Spain; Recruiting
      Hospital Universitario 12 de Octubre, Madrid,  28041,  Spain; Recruiting
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland; Recruiting
United Kingdom
      Selly Oak Hospital at University Hospital NHS Trust, Birmingham,  B29 6JD,  United Kingdom; Recruiting
United Kingdom, England
      Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust, Cambridge,  England,  CB2 2QQ,  United Kingdom; Recruiting
      Bristol Haematology and Oncology Centre, Bristol,  England,  BS2 8ED,  United Kingdom; Recruiting
      Broomfield Hospital, Chelmsford, Essex,  England,  CM1 5ET,  United Kingdom; Recruiting
      Cancer Research Centre at Weston Park Hospital, Sheffield,  England,  S1O 2SJ,  United Kingdom; Recruiting
      Cheltenham General Hospital, Cheltenham,  England,  GL53 7AN,  United Kingdom; Recruiting
      Clatterbridge Centre for Oncology NHS Trust, MERSEYSIDE,  England,  CH63 4JY,  United Kingdom; Recruiting
      James Cook University Hospital, Middlesbrough,  England,  TS4 3BW,  United Kingdom; Recruiting
      Mount Vernon Hospital, Northwood,  England,  HA6 2RN,  United Kingdom; Recruiting
      Northern Centre for Cancer Treatment at Newcastle General Hospital, Newcastle upon Tyne,  England,  NE4 6BE,  United Kingdom; Recruiting
      Nottingham City Hospital NHS Trust, Nottingham,  England,  NG5 1PB,  United Kingdom; Recruiting
      Poole Hospital NHS Trust, Poole Dorset,  England,  BH15 2JB,  United Kingdom; Recruiting
      Royal Free and University College Medical School, London,  England,  NW3 2QG,  United Kingdom; Recruiting
      Royal Marsden NHS FoundationTrust - London, London,  England,  SW3 6JJ,  United Kingdom; Recruiting
      Saint Bartholomew's Hospital, London,  England,  EC1A 7BE,  United Kingdom; Recruiting
      Salisbury District Hospital, Salisbury,  England,  SP2 8BJ,  United Kingdom; Recruiting
      Southampton General Hospital, Southampton,  England,  SO16 6YD,  United Kingdom; Recruiting
      Southend NHS Trust Hospital, Westcliff-On-Sea,  England,  SS0 0RY,  United Kingdom; Recruiting
      St. George's Hospital, London,  England,  SW17 0QT,  United Kingdom; Recruiting
      St. James's University Hospital at Leeds Teaching Hospital NHS Trust, Leeds,  England,  LS9 7TF,  United Kingdom; Recruiting
      St. Luke's Cancer Centre at Royal Surrey County Hospital, Guildford,  England,  GU2 5XX,  United Kingdom; Recruiting
United Kingdom, Scotland
      Ninewells Hospital and Medical School, Dundee,  Scotland,  DD1 9SY,  United Kingdom; Recruiting
      Western General Hospital, Edinburgh,  Scotland,  EH4 2XU,  United Kingdom; Recruiting
United Kingdom, Wales
      Velindre Cancer Center at Velinde Hospital, Cardiff,  Wales,  CF4 7XL,  United Kingdom; Recruiting
Yugoslavia
      Institute of Oncology and Radiology of Serbia, BELGRADE,  11000,  Yugoslavia; Recruiting

Study chairs or principal investigators

Alexander M.M. Eggermont, MD, PhD,  Daniel Den Hoed Cancer Center at Erasmus Medical Center   

Study ID Numbers:  CDR0000067645; EORTC-18961; BMS-CA152-003; NCT00005052
Record last reviewed:  March 2005
Last Updated:  March 21, 2005
Record first received:  April 6, 2000
ClinicalTrials.gov Identifier:  NCT00005052
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08