Gleevec Administered Preoperatively to Reduce Gastrointestinal Stromal Tumor (GIST)

A Phase II Study on Preoperative Administration of Gleevec in Patients With Initially Non-Resectable Gastrointestinal Stromal Tumor

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.

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.