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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Gastrointestinal Stromal Tumor (GIST)

Intervention / Treatment
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* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years of age or older. Patient must have had a histological diagnosis of primary GIST. The tumor must expressed KIT (CD117) protein by immunohistochemistry performed by central pathology. 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 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. 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. Performance status 0 or 1 (ECOG) 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 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. 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. Written, voluntary informed consent. Exclusion Criteria: Patient has metastatic GIST to the peritoneum, liver, lymph node, or other sites or recurrent GIST. Prior treatment for GIST with the exception of prior treatment with imatinib adjuvant lasting ≤ 8 weeks following gross surgical resection. Patient has received any other investigational agents within 28 days of first day of study drug dosing. 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) 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). Patient has a known diagnosis of human immunodeficiency virus (HIV) infection. Patient receiving concurrent treatment with warfarin (acceptable alternative: low-molecular weight heparin). Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent. -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imatinib<br>All subjects received in tablet form imatinib (STI571) 400 mg once daily. | Drug: imatinib mesylate<br>* imatinib mesylate was supplied in 100 and 400 mg tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free Survival up to 60 Months | Recurrence-free survival assessment is based on the radiologic evidence and is defined as the time from the date of first dose of imatinib to the date of the first documented disease recurrence or death due to any cause (event). | Baseline up to 60 months | 
| Kaplan-Meier Estimates for Recurrence-free Survival up to 60 Months | Recurrence-free survival (RFS) assessment is based on the radiologic evidence and is defined as the time from the date of first dose of imatinib to the date of the first documented disease recurrence or death due to any cause (event). RFS estimates were summarized using the Kaplan-Meier product-limit method (Kaplan 1958). Censoring rules for RFS with the earliest occurring rule used in the analysis: subjects without objective recurrence of disease who were alive at the time of their discontinuation from study were censored at the end of study date or end of treatment visit date if the subject refused to be followed post treatment and subjects recording antineoplastic therapy during the study were censored on the date of the therapy initiated | Baseline up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) at 60 Months | Overall survival was defined as the time from the date of the first dose of study drug to the date of death. Subjects who were alive at the time of discontinuation/completion of the study were censored at the end of study date or end of treatment visit date if the subject refused to be followed post treatment. Full analysis set. | Baseline up to approximately 60 months | 
| Kaplan-Meier Estimates for Overall Survival (OS) up to 60 Months | Overall survival was defined as the time from the date of the first dose of study drug to the date of death. Subjects who were alive at the time of discontinuation/completion of the study were censored at the end of study date or end of treatment visit date if the subject refused to be followed post treatment. Full analysis set. | Baseline up to appoximately 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Imatinib, Protein Kinase Inhibitors, Gastrointestinal Stromal Tumors, Digestive System Diseases, Digestive System Neoplasms, Gastrointestinal Diseases, Gastrointestinal Neoplasms, Adjuvant, PERSIST, PERSIS-5