RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving imatinib mesylate after surgery may kill any remaining tumor cells. It is not yet known whether imatinib mesylate is more effective than observation only in treating gastrointestinal stromal tumor.

PURPOSE: This randomized phase III trial is studying imatinib mesylate to see how well it works compared to observation only in treating patients who have undergone surgery for localized gastrointestinal stromal tumor.

Condition	Treatment or Intervention	Phase
gastrointestinal stromal tumor	Drug: imatinib mesylate  Procedure: adjuvant therapy  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase III

Further Study Details: 

OBJECTIVES: Primary

• Compare the effect of adjuvant imatinib mesylate vs observation only on the prognosis of patients with completely resected localized gastrointestinal stromal tumors at intermediate- or high-risk of relapse.
• Compare overall survival of patients treated with these regimens.

Secondary

• Compare relapse-free survival and relapse-free interval in patients treated with these regimens.
• Determine the safety of this drug in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, risk category (high vs intermediate), tumor site (gastric vs other), and resection level (R0 vs R1). Patients are randomized to 1 of 2 arms.

• Arm I: Patients receive adjuvant oral imatinib mesylate once daily for 2 years in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients are observed (without receiving further antitumoral therapy) every 3 months for 2 years. After completion of study treatment, patients in arm I are followed every 3 months for 2 years. All patients are then followed every 4 months for 3 years and at least annually thereafter.

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study within 5 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed gastrointestinal stromal tumor
• Localized disease
• Meets 1 of the following criteria:
• At high-risk of relapse, defined by 1 of the following criteria:
• Tumor size > 10 cm
• Mitotic rate > 10/50 high-power field (HPF)
• Tumor size > 5 cm AND mitotic rate > 5/50 HPF
• At intermediate-risk of relapse, defined by 1 of the following criteria:
• Tumor size < 5 cm AND mitotic rate 6-10/50 HPF
• Tumor size 5-10 cm AND mitotic rate < 5/50 HPF
• Tumor must stain positive for Kit (CD117) by polyclonal DAKO antibody staining
• Must have undergone complete resection of the primary tumor at least 2 weeks, but no more than 3 months, before study entry
• Meets criteria for 1 of the following resection levels:
• R0 (clear margins)
• R1, defined by 1 of the following criteria:
• Margins of resection are contaminated by tumor, but no macroscopic tumor is left behind
• Intraoperative tumor rupture
• Shelling-out procedure
• Endoscopic maneuver
• No residual macroscopic disease after surgery
• Regional positive lymph nodes allowed provided they have been macroscopically excised
• No distant metastases*, including any of the following:
• Peritoneal lesion not contiguous to the primary tumor
• Liver metastases
• Hemoperitoneal metastases NOTE: *Even if a complete resection (R0) was performed

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL (transfusions allowed)

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT ≤ 2.5 times ULN
• No uncontrolled liver disease
• No chronic viral hepatitis at risk of reactivation

Renal

• Creatinine < 1.5 times ULN
• No uncontrolled chronic renal disease

Cardiovascular

• No New York Heart Association class III-IV cardiac disease
• No congestive heart failure
• No myocardial infarction within the past 2 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for up to 3 months after study participation
• No uncontrolled diabetes
• No uncontrolled active infection
• No HIV infection
• No psychological, familial, sociological, or geographical condition that would preclude study compliance or participation
• No other severe and/or uncontrolled medical disease
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• No other prior molecular targeted or biologic therapy
• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) to support blood counts
• No concurrent anticancer biologic agents

Chemotherapy

• No prior chemotherapy
• No concurrent anticancer chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy
• No concurrent anticancer radiotherapy

Surgery

• See Disease Characteristics
• Prior non-curative surgery allowed (e.g., surgery with main diagnostic intent or emergency surgery with symptomatic intent)

Other

• No prior imatinib mesylate
• No prior randomization to this study
• No concurrent therapeutic anticoagulation with coumarin derivatives
• Concurrent therapeutic low-molecular weight heparin or mini-dose coumarin derivatives (equivalent to oral warfarin 1 mg/day) allowed for prophylaxis of central venous catheter thrombosis
• No other concurrent antitumoral therapy
• No other concurrent anticancer agents
• No other concurrent investigational drugs

Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium; Recruiting
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium; Recruiting
France
      Centre Eugene Marquis, Rennes,  35042,  France; Recruiting
      Centre Henri Becquerel, Rouen,  76038,  France; Recruiting
      Centre Hospitalier - Abbeville, Abbeville,  80101,  France; Recruiting
      Centre Hospitalier General, Pau,  64000,  France; Recruiting
      Centre Hospitalier Universitaire Bretonneau de Tours, Clermont-Ferrand,  63011,  France; Recruiting
      Centre Hospitalier Universitaire, Reims,  51092,  France; Recruiting
      Centre Jean Perrin, Clermont-Ferrand,  63011,  France; Recruiting
      Centre Paul Papin, Angers,  49036,  France; Recruiting
      Centre Paul Strauss, Strasbourg,  67065,  France; Recruiting
      Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle, Montpellier,  34298,  France; Recruiting
      Centre Regional Rene Gauducheau, Nantes-Saint Herblain,  44805,  France; Recruiting
      CHR de Besancon - Hopital Jean Minjoz, Besancon,  25030,  France; Recruiting
      CHR D'Orleans - Hopital de la Source, Orleans,  45067,  France; Recruiting
      CHR Hotel Dieu, Nantes,  44093,  France; Recruiting
      CHU Ambroise Pare, Boulogne-Billancourt,  F-92104,  France; Recruiting
      CHU de la Timone, Marseille,  13385,  France; Recruiting
      Hopital Andre Mignot, Le Chesnay,  78157,  France; Recruiting
      Hopital Charles Nicolle, Rouen,  76031,  France; Recruiting
      Hopital Edouard Herriot, Lyon,  69437,  France; Recruiting
      Hopital Europeen Georges Pompidou, Paris,  75015,  France; Recruiting
      Hopital Universitaire Hautepierre, Strasbourg,  67098,  France; Recruiting
      Institut Bergonie, Bordeaux,  33076,  France; Recruiting
Italy
      Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan,  20133,  Italy; Recruiting
Netherlands
      Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam,  1066 CX,  Netherlands; Recruiting

Study chairs or principal investigators

Paolo G. Casali, MD,  Istituto Nazionale per lo Studio e la Cura dei Tumori   
Paolo G. Casali, MD,  Istituto Nazionale per lo Studio e la Cura dei Tumori   
Axel Le Cesne, MD,  Institut Gustave Roussy   
Andres Poveda, MD,  Instituto Valenciano De Oncologia   

Study ID Numbers:  CDR0000410825; EORTC-62024; ISG-62024; FRE-FNCLCC-EORTC-62024; GEIS-EORTC-62024; EUDRACT-2004-001810-16; NCT00103168
Record last reviewed:  March 2005
Last Updated:  March 21, 2005
Record first received:  February 7, 2005
ClinicalTrials.gov Identifier:  NCT00103168
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08