Five Year Adjuvant Imatinib Mesylate (Gleevec®) in Gastrointestinal Stromal Tumor (GIST)

A Phase II, Non-Randomized, Open-Label Multicenter Study of 5 Year Adjuvant Imatinib Mesylate (Gleevec®) in Patients at Significant Risk for Recurrence Following Complete Resection of Primary Gastrointestinal Stromal Tumor (GIST)

This is a Phase II, non-randomized, open-label, multi-center study conducted in the USA. The purpose of this trial is to evaluate the use of long term adjuvant imatinib mesylate in patients at significant risk for recurrence following complete resection of primary GIST.

This is a Phase II, non-randomized, open-label, multi-center study conducted in the USA. The primary endpoint is to evaluate the use of long term adjuvant imatinib mesylate in patients at significant risk for recurrence following complete resection of primary GIST. A total of 85 adult patients, 18 years of age and older will be enrolled.Participants will take 400 mg of imatinib mesylate daily by mouth for a total of 5 years. At the conclusion of the treatment period, patients will be followed for 2 years for survival, status of response and antineoplastic treatments and quality of life.

Inclusion Criteria:

1. Patients 18 years of age or older.

2. Patient must have had a histological diagnosis of primary GIST.

3. The tumor must expressed KIT (CD117) protein by immunohistochemistry performed by central pathology.

4. Patient must have been at significant risk of tumor recurrence as defined by either:

   • Primary GIST (any site): ≥ 2 cm and a mitotic rate of ≥ 5/50 HPF's
   • Non-gastric primary GIST: ≥ 5cm

5. Patient must have undergone complete gross resection of a primary GIST within 12 weeks prior to first dose of imatinib study drug. The inclusion of R1 resections will be reviewed on a case by case basis by the Study Management Committee.

6. Patient must had no evidence of metastatic GIST on either 1) a post-operative CT of the abdomen and pelvis with intravenous and oral contrast or 2) MRI of the abdomen and pelvis with intravenous contrast. CT or MRI must have been performed within 8 weeks prior to first dose of imatinib study drug.

7. Performance status 0 or 1 (ECOG)

8. Patient must had the following post-operative laboratory values confirmed within 14 days prior to first dose of imatinib study drug:

   • total bilirubin < 1.5 x ULN NOTE: Patients with elevated bilirubin secondary to Gilbert's disease are eligible to participate in the study.
   • ALT and AST < 2.5 x ULN
   • creatinine < 1.5 x ULN
   • ANC > 1.5 x 109/L
   • platelets > 100 x 109/L

9. If patient is a cancer survivor, ALL of the following criteria apply:

   • Patient had undergone potentially curative therapy for all prior malignancies.
   • No evidence of any prior malignancies for at least 3 years with no evidence of recurrence (except for effectively treated basal cell or squamous carcinoma of the skin, carcinoma in-situ of the cervix that has been effectively treated by surgery alone, or lobular carcinoma in-situ of the ipsilateral or contralateral breast treated by surgery alone).
   • Patient is deemed by their treating physician to be at low risk for recurrence from prior malignancies.

10. Female patients of childbearing potential must have had negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Female patients of reproductive potential must have jagreed to employ an effective barrier method of birth control throughout the study and for up to 7 days following discontinuation of study drug.

11. Written, voluntary informed consent.

Exclusion Criteria:

1. Patient has metastatic GIST to the peritoneum, liver, lymph node, or other sites or recurrent GIST.

2. Prior treatment for GIST with the exception of prior treatment with imatinib adjuvant lasting ≤ 8 weeks following gross surgical resection.

3. Patient has received any other investigational agents within 28 days of first day of study drug dosing.

4. Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)

5. Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risk or compromise compliance with the protocol (i.e., uncontrolled diabetes, chronic renal disease, chronic liver disease, or active uncontrolled infection).

6. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.

7. Patient receiving concurrent treatment with warfarin (acceptable alternative: low-molecular weight heparin).

8. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

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