Imatinib Mesylate or Observation Only in Treating Patients Who Have Undergone Surgery for Localized Gastrointestinal Stromal Tumor

OBJECTIVES:

Primary

• Assess whether there is a difference in overall survival between intermediate and high-risk localized GIST patients undergoing complete surgery alone and those undergoing complete surgery plus adjuvant imatinib mesylate 400 mg daily for two years Secondary
• Assess whether there is a difference in relapse-free survival and relapse-free interval between GIST undergoing complete surgery alone and those undergoing surgery + adjuvant Imatinib mesylate 400 mg daily for two years.
• 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).

• 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 900 patients will be accrued for this study within 3.5 years.

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 for gastrointestinal stromal tumors
• 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