Gleevec Administered Preoperatively to Reduce Gastrointestinal Stromal Tumor (GIST)

• Clinical response to treatment
• Radiological response to treatment
• Pathological response to treatment
• Compare clinical with pathological response
• Evaluate the impact of Gleevec on surgical morbidity
• Evaluate disease-free survival
• Evaluate overall survival
• Evaluate whether the response rate can predict survival

The aim of this study is to demonstrate that the use of Gleevec in initially non-resectable gastrointestinal stromal tumors can lead to allow complete resection in 20% of cases.

Gastrointestinal stromal tumor (GIST) is a specific, immunohistochemically KIT+ mesenchymal neoplasm of the gastrointestinal tract. The identification of KIT+ tumor has become more important after introduction of target treatment with KIT tyrosine kinase inhibitor Imatinib mesylate (Gleevec). Despite this progress, GIST patients presenting a tumor larger than 5 cm have a 10 year survival between 10% and 30%. Indeed, the risk of microscopic spreading of the tumor during surgery is very high since intra-abdominal organs are in close relation to each others. To improve survival, it seemed logical to use preoperative Gleevec to reduce tumor size and improve efficacy of the surgical procedure.

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Inclusion Criteria:

• GIST patient considered initially non-resectable as defined by one of the following:

  1. when the surgical team considers that the risk of incomplete resection (R1 or R2) of a GIST is higher than 20%
  2. when the resection of a GIST necessitates a highly morbid procedure
  3. when a GIST is attached to 3 or more major intra-abdominal structures or to a major intra-abdominal blood vessel
  4. when GIST is considered at very high risk of recurrence. This is the case when it is a recurrence or when the tumor is in very close contact with a structure that cannot be resected by surgery or when the patient has metastasis.
• Outpatient is 18 years old or more
• ECOG performance status 0, 1 or 2
• Immunohistochemical confirmation of KIT overexpression must exist at the study entry
• Measurable disease on CT-Scan or MRI (ultrasound and/or operative finding are not acceptable) and response to RECIST criteria
• Have a life expectancy of at least 6 months
• Be willing and able to comply with the protocol (and surgery if required) for the duration of the study
• Give written informed consent prior to study-specific screening procedure, with the understanding that the patient has the right to withdraw from the study at any time without prejudice

Exclusion Criteria:

• received Imatinib in the past
• received a full course of radiotherapy within 3 months of inclusion in the study. A short course of radiotherapy to control bleeding is allowed.
• received systemic chemotherapy within 4 weeks of inclusion in the study
• received steroids for less than 4 weeks of inclusion in the study
• pregnant or lactating women
• women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
• sexually active males or females (of childbearing potential) unwilling to practice contraception during the study
• history of other malignancy within the past 5 years, except cured basal cell carcinoma of skin and cured carcinoma in-situ of uterine cervix
• clinical or other evidence of CNS metastases
• myocardial infarction within the last 3 months
• any medical condition that contraindicates potential surgery
• lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome or inability to take oral medication
• any serious uncontrolled concomitant disease

• any of the following laboratory values:

  1. absolute neutrophil count < 1.5 E+09/L
  2. platelet count < 80000 E+09/L
  3. AST or ALT higher than 2 X normal
• major surgery within 4 weeks prior to start of study treatment, or lack of complete recovery from effects of major surgery
• patients with known or suspected hypersensitivity to one of the Gleevec components.