Imatinib Mesylate in Treating Patients With Locally Advanced Gastrointestinal Stromal Tumor

Study Overview
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Brief Summary
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RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving imatinib mesylate before surgery may shrink the tumor so that it can be removed. PURPOSE: This phase II trial is studying how well imatinib mesylate works in treating patients with locally advanced gastrointestinal stromal tumor.

Detailed Description
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OBJECTIVES: Primary Determine radiographic objective response rates in patients with locally advanced gastrointestinal stromal tumor treated with neoadjuvant imatinib mesylate. Determine histological response in patients treated with this drug. Secondary Determine R0-resectability and organ-preserving resectability in these patients after treatment with this drug. Correlate radiographic imaging and metabolic imaging with histological response in patients treated with this drug. Determine the safety and tolerability of this drug in these patients. OUTLINE: This is a nonrandomized, open-label, multicenter study. Patients receive oral imatinib mesylate once or twice daily for 4-6 months in the absence of disease progression or unacceptable toxicity. Within 2-3 weeks after completion of imatinib mesylate, patients with responding or stable disease undergo surgical resection. After completion of study treatment, patients are followed at 4 weeks, 6 months, and then at 1 year. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Official Title
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Open-Label Trial of Neoadjuvant Imatinib Mesylate (Glivec) in Patients With Locally Advanced Malignant Gastrointestinal Stromal Tumors (GIST) Expressing c-Kit or Platelet-Derived Growth Factor Receptor-alpha

Conditions
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Gastrointestinal Stromal Tumor

Intervention / Treatment
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* Drug: imatinib mesylate
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed gastrointestinal stromal tumor Locally advanced disease Potentially resectable disease* No tumor that can be completely resected (R0) with sufficient margins NOTE: *Multivisceral resection may be necessary Tumor must stain positive for c-Kit (CD117) or platelet-derived growth factor receptor-alpha (PDGFRA) by immunohistochemistry At least 1 site of measurable disease No known brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-3 Life expectancy Not specified Hematopoietic Platelet count > 100,000/mm^3 Absolute neutrophil count > 1,500/mm^3 Hepatic AST and ALT < 2.5 times upper limits of normal (ULN) (5 times ULN if hepatic metastases are present) Bilirubin < 1.5 times ULN No chronic active hepatitis No cirrhosis No other chronic liver disease Renal Creatinine < 1.5 times ULN No chronic renal disease Cardiovascular No New York Heart Association class III-IV cardiac disease No congestive heart failure No myocardial infarction within the past 6 months Immunology No active uncontrolled infection No known HIV positivity Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for 3 months after completion of study treatment Must be medically fit to undergo surgery No other primary malignancy within the past 5 years except basal cell skin cancer, carcinoma in situ of the cervix, or a primary malignancy that is not currently clinically significant and does not require active intervention No gastrointestinal obstruction or major bleeding episode requiring immediate surgical intervention No uncontrolled diabetes No other severe or uncontrolled medical disease No significant history of noncompliance to medical regimens PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent anticancer biologic agents Chemotherapy More than 4 weeks since prior chemotherapy (6 weeks for nitrosourea or mitomycin) unless disease is rapidly progressing No concurrent anticancer chemotherapy Endocrine therapy No concurrent systemic corticosteroid therapy unless approved by the study sponsor Radiotherapy More than 4 weeks since prior radiotherapy No prior radiotherapy to ≥ 25% of bone marrow Surgery More than 2 weeks since prior major surgery except tumor biopsy Other More than 4 weeks since prior investigational drugs unless disease is rapidly progressing No other concurrent anticancer therapy No other concurrent investigational agents No concurrent warfarin for therapeutic anticoagulation Concurrent low molecular weight heparin (e.g., enoxaparin sodium) or heparin for therapeutic anticoagulation allowed Concurrent mini-dose warfarin (e.g.,1 mg/day) for prophylaxis of central venous catheter thrombosis allowed

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: imatinib mesylate|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall tumor response (complete response, partial response, stable disease, and progression of disease) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression of disease |  |  | 
| Overall survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastrointestinal stromal tumor