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

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase

Completed

Phase 3

Conditions

Gastrointestinal Stromal Tumor

Treatments

Drug: imatinib mesylate

Study type

Interventional

Funder types

Other

NETWORK

Identifiers

NCT00103168

GEIS-EORTC-62024

EORTC-62024

FRE-FNCLCC-EORTC-62024

ISG-62024

2004-001810-16 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

908 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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 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