Surgery for Locally Unresectable Advanced GISTs Without Metastasis After Imatinib Therapy

Study Overview
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Brief Summary
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Gastrointestinal stromal tumors (GISTs) are a form of sarcoma and the most common sarcoma tumors of the gastrointestinal tract. The limited clinical experience suggests that GIST patients may benefit from neo-adjuvant therapy from primary GIST. This is a prospective, multicenter, open, observational study in evaluation of safety and efficacy of imatinib compared with that of historical data for locally unresectable advanced GIST without metastasis. The study will include an up to 28-day screening period, followed by receiving imatinib mesylate (400 mg/day) for at least 6-12 months and followed up for 3 years after surgery.

Detailed Description
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Primary Objective To observe the safety of imatinib compared with that of historical data for locally unresectable advanced GIST without metastasis. Secondary Objective Progression-free survival (PFS) in resected patients during follow up R0 resection rate objective response rate, tumor shrinkage rate Correlation of mutation status with response Correlation of PK with response Surgical morbidity and mortality and safety follow up Quality of life Overall survival (OS)

Official Title
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A Trial for Surgical Treatment in Patients With Initially Locally Unresectable Advanced GIST Without Metastasis During Therapy With Imatinib

Conditions
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Gastrointestinal Stromal Tumor

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Locally advanced unresectable GIST without metastasis at EC junction requiring total gastrectomy, Duodenum requiring Whipple operation; Large GIST requiring multiviceral resection; Rectum: requiring APR. Histologically documentation with positive immunostaining for KIT (CD117) Patient age ≥ 18 years old ECOG performance status 0 or 1 Patient must have the following post-operative laboratory values confirmed within 14 days prior to registration: Creatinine ≤ 1.5 times the institution ULN (upper limit of normal) WBC ≥ 3,000/mm3 Platelets ≥ 100,000/mm3 Total Bilirubin ≤ 1.5 times the institution ULN. NOTE: Patients with elevated bilirubin secondary to Gilbert's disease are eligible to participate in the study. AST ≤ 2.5 times the institution ULN ALT ≤ 2.5 times the institution ULN Female of childbearing potential must have negative serum pregnancy test. -- -NOTE: Post-menopausal women must be amenorrheic for at least 12 months to be deemed not of reproductive potential. Patient is willing to sign informed consent. Exclusion Criteria Patient has received post-operative chemotherapy. Patient has received post-operative radiation therapy. Patient has received post-operative investigational treatment. Patient has received prior therapy with imatinib, or any other molecular targeted or biological therapy. Patient has had an active infection requiring antibiotics within 14 days prior to registration. any prior malignancies for at least 5 years with potential 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 risk for recurrence from prior malignancies.New York Heart Association Class 3 or 4 cardiac diseases. Patient is taking full dose warfarin. NOTE: The use of mini-dose warfarin (1 mg orally per day) for prevention of central line-associated deep venous thrombosis is permitted. Presence of severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal disease, uncontrolled liver disease, including chronic viral hepatitis judged at risk of reactivation, uncontrolled active infection, such as HIV infection, etc.). Patient, if female and breastfeeding. NOTE: It is not known whether imatinib or its metabolites are excreted in human milk.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Imatinib treat<br>• Locally advanced unresectable GIST without metastasis at EC junction requiring total gastrectomy, Duodenum requiring Whipple operation; Large GIST requiring multiviceral resection; Rectum: requiring APR. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | Evidence of measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines with CT scan. | five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate | all the participants | three years | 
| Objective response rate, tumor shrinkage rate | all the participants | three years | 
| Correlation of PK with response | check PK (trough level of imatinib)of all the participants at first month and every three months later to correlate with the response and check PK (peak level of imatinib) of all the participants who had adverse events | three years | 
| Surgical morbidity and mortality and safety follow up | surgical morbidity: morbidity related to surgical procedure surgical mortality: mortality related to surgical procedure safety: adverse events related imatinib according to NIH toxicity evaluation criteria | five years | 
| Overall survival (OS) | Overall survival (OS) will be measured from after administration of imatinib mesylate and death as the end point of the study, whatever the cause. Alive patients will be censored at the date of last follow-up. Causes of death will be recorded. | five years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastrointestinal stromal tumor, GIST, neoadjuvant, imatinib