Imatinib Mesylate in Treating Patients With Locally Advanced Gastrointestinal Stromal Tumor

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.

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