Clinical trial NCT00005052: Vaccine Therapy in Treating Patients With Primary Stage II Melanoma
Official title: Adjuvant Ganglioside GM2-KLH/QS-21 Vaccination: Post-Operative Adjuvant Ganglioside GM2-KLH/QS-21 (BMS-248479) Vaccination Treatment After Resection of Primary Cutaneous Melanoma Thicker Than 1.5mm (AJCC/UICC Stage II, T3-T4N0M0), a 2-Arm Multicenter Randomized Phase III Trial vs. Observation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Melanoma (Skin)
Keywords: stage II melanoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: Disease-free survival
Secondary outcomes:
measure: Duration of survival
measure: Toxicity as assessed by CTC v2
Other outcomes:
Locations:
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Haine Saint Paul
country: Belgium
facility: Hopital de Jolimont
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Aarhus
country: Denmark
facility: Aarhus University Hospital - Aarhus Sygehus - Norrebrogade
city: Copenhagen
country: Denmark
facility: Rigshospitalet - Copenhagen University Hospital
city: Copenhagen
country: Denmark
facility: Herlev Hospital - University Hospital of Copenhagen
city: Odense
country: Denmark
facility: Odense University Hospital
city: Tallinn
country: Estonia
facility: North-Estonian Regional Hospital Surgical Oncology Centre
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Besancon
country: France
facility: CHR de Besancon - Hopital Saint-Jacques
city: Boulogne Billancourt
country: France
facility: CHU Ambroise Pare
city: Caen
country: France
facility: CHU de Caen
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Lille
country: France
facility: Centre Hospitalier Regional et Universitaire de Lille
city: Montpellier
country: France
facility: Hopital St. Eloi
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nice
country: France
facility: Hopital L'Archet - 2
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard
city: Paris
country: France
facility: Hopital Saint-Louis
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Thionville
country: France
facility: Centre Hospitalier Regional Metz Thionville
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Hamburg
country: Germany
facility: Haematologisch-Onkologische Praxis Altona
city: Wuerzburg
country: Germany
facility: Universitaets-Hautklinik Wuerzburg
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico - Aviano
city: Firenze
country: Italy
facility: Ospendale S.M. Annunziata-A.S.DI Florence
city: Genoa (Genova)
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
city: Milano (Milan)
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: European Institute of Oncology
city: Naples
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Rome
country: Italy
facility: Ospedale S. Camillo-Forlanini
city: Rome
country: Italy
facility: Istituto Regina Elena
city: Torino
country: Italy
facility: Universita Degli Studi di Turin
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Nijmegen Cancer Center at Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Daniel Den Hoed Cancer Center at Erasmus Medical Center
city: Oslo
country: Norway
facility: Norwegian Radium Hospital
city: Poznan
country: Poland
facility: Great Poland Cancer Center
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia Centro do Porto, S. A.
city: Santarem
country: Portugal
facility: Hospital Distrital De Santarem
city: Moscow
country: Russian Federation
facility: Russian Academy of Medical Sciences Cancer Research Center
city: Belgrade
country: Serbia
facility: Institute of Oncology and Radiology of Serbia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
state: England
city: Chelmsford, Essex
country: United Kingdom
facility: Broomfield Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Royal Free and University College Medical School
state: England
city: London
country: United Kingdom
facility: St. George's Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - London
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Trust
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Poole Dorset
country: United Kingdom
facility: Poole Hospital NHS Trust
state: England
city: Salisbury
country: United Kingdom
facility: Salisbury District Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend NHS Trust Hospital
state: England
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velinde Hospital
state: Wales
city: Birmingham
country: United Kingdom
facility: Selly Oak Hospital at University Hospital NHS Trust
Study officials:
affiliation: Daniel Den Hoed Cancer Center at Erasmus Medical Center
name: Alexander M. M. Eggermont, MD, PhD
References:
citation: Eggermont AM, Suciu S, Ruka W, et al.: EORTC 18961: Post-operative adjuvant ganglioside GM2-KLH21 vaccination treatment vs observation in stage II (T3-T4N0M0) melanoma: 2nd interim analysis led to an early disclosure of the results. [Abstract] J Clin Oncol 26 (Suppl 15): A-9004, 2008.
citation: Patel PM, Suciu S, Mortier L, Kruit WH, Robert C, Schadendorf D, Trefzer U, Punt CJ, Dummer R, Davidson N, Becker J, Conry R, Thompson JA, Hwu WJ, Engelen K, Agarwala SS, Keilholz U, Eggermont AM, Spatz A; EORTC Melanoma Group. Extended schedule, escalated dose temozolomide versus dacarbazine in stage IV melanoma: final results of a randomised phase III study (EORTC 18032). Eur J Cancer. 2011 Jul;47(10):1476-83. doi: 10.1016/j.ejca.2011.04.030. Epub 2011 May 18.