Study Comparing 12 Months Versus 36 Months of Imatinib in the Treatment of Gastrointestinal Stromal Tumor (GIST)

In this study, patients who have been diagnosed with gastrointestinal stromal tumor (GIST) will be randomly allocated in a 1:1 ratio to receive imatinib (Gleevec) either for 12 or for 36 months following surgery. The study participants are required to have a histologically verified GIST with a high risk of GIST recurrence despite complete removal of all macroscopic GIST tissue at surgery. The high/very high risk of recurrence is defined as one of the following: 1) the largest tumor diameter is over 10 cm; 2) the mitosis count is high (over 10 mitoses per 50 high power microscope fields, HPFs); 3) the largest tumor diameter over 5 cm and the mitosis count is over 5/50 HPFs; 4) tumor spillage has taken place into the abdominal cavity at the time of surgery or following spontaneous tumor rupture. All study participants will receive imatinib 400 mg/day orally, but the duration of imatinib administration will be determined randomly (either for 12 or for 36 months). The study participants will be followed up using blood tests and computed tomography (or MRI) of the abdomen. The computed tomography examinations will be performed at 6 month intervals for a median of 5 years. A total of 280 patients will be entered into the study. The study hypothesis is that adjuvant imatinib may prevent some of the GIST recurrences, and that there may be a difference in the rate of GIST recurrence between the two groups.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Age 18 or older
* Histologically documented diagnosis of GIST
* Resectable GIST
* GIST removed at open surgery
* Immunohistochemical documentation of GIST (immunostaining for KIT/CD117)
* High risk of tumor recurrence as defined as one of the following: 1) the largest tumor diameter greater than 10.0 cm (measured by a pathologist, with any mitotic count); 2) mitotic count over 10 mitoses per 50 high power fields (HPFs) (with any tumor size); the largest tumor diameter larger than 5.0 cm and the mitotic count is over 5/50 HPFs; 4) tumor spillage into the abdominal cavity at surgery (or tumor rupture). No residual tumors must be present at laparotomy, or in postoperative CT or MRI examinations. Patients who have microscopically infiltrated margins (or suspected microscopical infiltration, R1) are also allowed to enter study.
* Performance status 0, 1, or 2 (ECOG)
* Adequate organ function, defined as follows: total bilirubin \<1.5 x ULN (upper limit of normal), serum AST (SGOT) and ALT (SGPT) \<2.5 x ULN, creatinine \<1.5 x ULN, ANC (neutrophil count) \>1.5 x 10\^9/L, platelets \>100 x 10\^9/L.
* Negative pregnancy test (females with childbearing potential)
* Written, voluntary informed consent

Exclusion Criteria:

* Inoperable or metastatic GIST
* Less than 1 week or more than 12 weeks has elapsed from surgery
* Recurrent GIST
* Patient has received any investigational agents within 28 days as calculated from the first day of the study drug dosing
* Patient is less than 5 years free from another primary malignancy
* Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria
* Female patients who are pregnant or breast-feeding
* Patient has severe or uncontrolled medical disease (i.e. uncontrolled diabetes, severe chronic renal disease, or active uncontrolled infection). Concurrent use of warfarin or acetaminophen are not allowed with imatinib.
* Chronic liver disease
* Known diagnosis of human immunodeficiency virus (HIV) infection
* Patient has received chemotherapy for GIST
* Patient has received neoadjuvant imatinib therapy prior to randomization
* Radiotherapy to 25% or more of the bone marrow
* Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent

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