Three Versus Five Years of Adjuvant Imatinib as Treatment of Patients With Operable GIST

Prior treatment

• Prior adjuvant (+ neoadjuvant) therapy with imatinib mesylate for at least 35 months has not been completed, or the total duration of prior adjuvant (+ neoadjuvant) imatinib administration exceeds the total duration of 37 months.
• Patient has received any investigational anti-cancer agents during adjuvant imatinib or between completion of adjuvant imatinib and the date of randomization.

Other illness

• Patient has been free of another malignancy for less than 5 years except if the other malignancy is not currently clinically significant nor requiring active intervention, or if the other malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Recent existence of any other malignant disease is not allowed.
• Patient with Grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., congestive heart failure, myocardial infarction within 6 months of study entry).
• Severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, severe chronic renal disease, or active uncontrolled infection).
• Known diagnosis of human immunodeficiency virus (HIV) infection.
• Patient with a significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Other

• Presence of distant metastases or local recurrence of GIST.
• Not willing to donate tumor tissue and/or blood samples for the study molecular studies.
• Presence of a substitution mutation at PDGFRA codon D842 (usually D842V).
• Administration of adjuvant imatinib longer than for 3 years is planned regardless of the result of randomization, or "life long" imatinib administration is planned.
• Neoadjuvant imatinib for a duration that exceeds 9 months.
• Longer than 4-week break during adjuvant imatinib administration.
• The dose of imatinib at completion of 3 years of adjuvant imatinib was 200 mg per day or less or greater than 800 mg per day.
• Female patients who are pregnant or breast-feeding.

• Age ≥ 18 years.
• Morphological and immunohistological documentation of GIST (immunostaining for KIT and/or DOG-1 positive, or mutation of KIT or PDGFRA present in tumor tissue).
• Macroscopically complete surgical resection of GIST (either R0 or R1 resection).
• Mutation analysis of KIT and PDGFR genes has been carried out.
• A high risk of GIST recurrence; either gastric GIST with mitotic count \>10/50 HPFs, or non-gastric GIST with mitotic count \>5/50 HPFs, or tumor rupture.
• Eastern Cooperative Oncology Group performance status ≤ 2.
• Adequate organ function.
• Female patients of childbearing potential must have a negative pregnancy test within 14 days before initiation of study drug dosing. Postmenopausal women must have amenorrhea for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
• Patient willing to be followed up at the study site regardless of the result of randomization.
• Patient has provided a written, voluntary informed consent prior to study-specific screening procedures.