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.

Condition	Treatment or Intervention	Phase
gastrointestinal stromal tumor	Drug: imatinib mesylate  Procedure: conventional surgery  Procedure: enzyme inhibitor therapy  Procedure: neoadjuvant therapy  Procedure: protein tyrosine kinase inhibitor therapy  Procedure: surgery	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Please refer to this study by ClinicalTrials.gov identifier  NCT00112632

Austria
      Allgemeines Krankenhaus der Stadt Wien, Vienna,  A-1090,  Austria; Recruiting
Germany
      Dr. Horst-Schmidt-Kliniken, Wiesbaden,  D-65199,  Germany; Recruiting
      Eberhard Karls Universitaet, Tuebingen,  D-72076,  Germany; Recruiting
      Klinik & Poliklinik fur Strahlentherapie der Universitat zu Koln, Koln,  D-50924,  Germany; Recruiting
      Klinikum Grosshadern der Ludwig-Maximilians Universitaet Muenchen, Munich,  D-81377,  Germany; Recruiting
      Klinikum Rechts Der Isar - Technische Universitaet Muenchen, Munich,  D-81675,  Germany; Recruiting
      Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch, Berlin,  D-13122,  Germany; Recruiting
      Universitaetsklinikum Bonn, Bonn,  D-53105,  Germany; Recruiting
      Universitaets-Krankenhaus Eppendorf, Hamburg,  D-20246,  Germany; Recruiting

Study chairs or principal investigators

Thomas Licht,  Study Chair,  Technische Universitaet Muenchen   

Study ID Numbers:  CDR0000430499; KRDI-TUM-GIST-CST1571-BDE43; EU-20507
Record last reviewed:  May 2005
Last Updated:  June 2, 2005
Record first received:  June 2, 2005
ClinicalTrials.gov Identifier:  NCT00112632
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-06-07