• Biological effects of imatinib mesylate [ Designated as safety issue: No ]
• Rate of disease recurrence at 2 years [ Designated as safety issue: No ]
• Rates of objective response (complete, partial, and stable) [ Designated as safety issue: No ]
• Major toxicity (i.e., grade ≥ 3) [ Designated as safety issue: Yes ]
• Correlation of glucose transported expression and positron emission tomography (PET) interpretations [ Designated as safety issue: No ]
• Tumor changes observed on PET and correlation with size changes observed on conventional cross-sectional imaging [ Designated as safety issue: No ]
• Diagnostic accuracy of PET to predict disease recurrence [ Designated as safety issue: No ]

• Biological effects of imatinib mesylate
• Rate of disease recurrence at 2 years
• Rates of objective response (complete, partial, and stable)
• Major toxicity (i.e., grade ≥ 3)
• Correlation of glucose transported expression and positron emission tomography (PET) interpretations
• Tumor changes observed on PET and correlation with size changes observed on conventional cross-sectional imaging
• Diagnostic accuracy of PET to predict disease recurrence

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving imatinib mesylate before and after surgery may shrink the tumor so it can be removed and may kill any tumor cells remaining after surgery.

PURPOSE: Phase II trial to study the effectiveness of neoadjuvant and adjuvant imatinib mesylate in treating patients who are undergoing surgery for primary or recurrent malignant gastrointestinal stromal tumor.

OBJECTIVES:

• Determine the progression-free survival of patients with primary or recurrent potentially resectable malignant gastrointestinal stromal tumor treated with neoadjuvant and adjuvant imatinib mesylate.
• Determine the objective response rate of patients treated with this drug.
• Determine the safety of this drug in these patients.

OUTLINE: Patients receive oral imatinib mesylate once daily. Treatment continues for 8 weeks in the absence of disease progression. Patients with disease progression are considered for immediate surgical resection. Otherwise, after 8 weeks, patients undergo surgical resection to debulk all gross tumor. Two to four weeks after surgery, patients receive oral imatinib mesylate once daily for 2 years.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 63 patients will be accrued for this study within 2 years.

• Drug: imatinib mesylate
• Procedure: adjuvant therapy
• Procedure: conventional surgery
• Procedure: neoadjuvant therapy

• Eisenberg BL, Harris J, Blanke CD, Demetri GD, Heinrich MC, Watson JC, Hoffman JP, Okuno S, Kane JM, von Mehren M. Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): Early results of RTOG 0132/ACRIN 6665. J Surg Oncol. 2008 Oct 21; [Epub ahead of print]
• Rink L, Skorobogatko Y, Kossenkov AV, Belinsky MG, Pajak T, Heinrich MC, Blanke CD, von Mehren M, Ochs MF, Eisenberg B, Godwin AK. Gene expression signatures and response to imatinib mesylate in gastrointestinal stromal tumor. Mol Cancer Ther. 2009 Aug;8(8):2172-82. Epub 2009 Aug 11.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant gastrointestinal stromal tumor

  • Potentially resectable primary disease OR

  • Potentially resectable recurrent disease

    • Local or intra-abdominal/pelvic metastatic disease
• Documented c-kit (CD117) expression by immunohistochemical analysis of either initial core specimen or, if recurrent disease, from original tumor block
• Primary disease must be visceral, intra-abdominal, or pelvic in origin

• At least 1 unidimensionally measurable lesion

  • At least 5 cm for primary disease
  • At least 2 cm for recurrent disease
• At least 1 viable core biopsy tumor specimen obtained within 8 weeks before registration

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• ALT/AST no greater than 2.5 times ULN
• No uncontrolled chronic liver disease

Renal:

• Creatinine no greater than 1.5 times ULN
• No uncontrolled chronic renal disease

Cardiovascular:

• No New York Heart Association class III or IV cardiac disease

Other:

• Must be able to lie still in the PET scanner for approximately 1-2 hours
• No uncontrollable hyperglycemia
• No medical or psychological condition that would preclude study participation
• No severe or uncontrolled medical disease
• No active uncontrolled infection
• No known or suspected hypersensitivity to any component of the study drug
• Any prior malignancy is allowed provided patient remains disease free from that malignancy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 28 days since prior biologic therapy
• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy:

• At least 28 days since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 28 days since prior radiotherapy

Surgery:

• See Disease Characteristics

Other:

• At least 28 days since prior investigational drugs
• At least 28 days since prior imatinib mesylate
• No concurrent therapeutic doses of warfarin
• Concurrent low-molecular weight heparin or mini-dose warfarin (1 mg per day) prophylaxis is allowed

• National Cancer Institute (NCI)
• American College of Radiology Imaging Network
• Eastern Cooperative Oncology Group