RATIONALE: Imatinib mesylate (Gleevec; STI571) may interfere with the growth of tumor cells and may be an effective treatment for patients with primary gastrointestinal stromal tumor that has been completely removed by surgery.

PURPOSE: This randomized phase III trial is studying imatinib mesylate (Gleevec; STI571) to see how well it works compared to placebo in treating patients with primary gastrointestinal stromal tumor that has been completely removed by surgery.

Condition	Treatment or Intervention	Phase
gastrointestinal stromal tumor	Drug: imatinib mesylate  Procedure: adjuvant therapy  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the overall and recurrence-free survival of patients with resected primary gastrointestinal stromal tumor treated with adjuvant imatinib mesylate (Gleevec; STI571) vs placebo.
• Determine the safety and efficacy of adjuvant imatinib mesylate in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, crossover, multicenter study. Patients are stratified according to tumor size (3 cm but less than 6 cm vs 6 cm to less than 10 cm vs 10 cm or greater). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral imatinib mesylate (Gleevec; STI571) once daily. Treatment continues for 1 year in the absence of unacceptable toxicity. Patients who develop a recurrence during the year of initial treatment receive imatinib mesylate (Gleevec; STI571) at an increased dose. Patients who develop a recurrence after the year of initial treatment restart imatinib mesylate (Gleevec; STI571) and continue taking the drug at the discretion of the principal investigator.
• Arm II: Patients receive oral placebo once daily. Treatment continues for 1 year in the absence of unacceptable toxicity. Patients who develop a recurrence at any time discontinue placebo and crossover to arm I. Treatment on arm I continues at the discretion of the principal investigator. Patients are followed every 3 months for 2 years and then every 6 months for 8 years.

PROJECTED ACCRUAL: A total of 489 patients will be accrued for this study within 3.8 years.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary gastrointestinal tumor (GIST)
• Tumor size at least 3 cm in maximum dimension
• No peritoneal or distant metastasis
• Prior complete gross resection of a primary GIST within the past 14-70 days
• R0 resection (negative microscopic margins) OR
• R1 resection (positive microscopic margins)
• Tumor must stain positive for Kit receptor tyrosine kinase by immunohistochemistry using the Dako anti-CD117 antibody
• No objective evidence of residual disease on the postoperative CT scan or MRI of the abdomen or pelvis

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN) (unless elevation is secondary to Gilbert's disease)
• AST and ALT no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

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

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after study participation
• No other malignancy within the past 5 years except:
• Effectively treated basal cell or squamous cell skin cancer
• Carcinoma in situ of the cervix effectively treated by surgery alone
• Lobular carcinoma in situ of the ipsilateral or contralateral breast treated by surgery alone
• Prior malignancies must be deemed at low risk for recurrence
• No active infection requiring antibiotics within the past 14 days

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No concurrent anticancer biologic agents

Chemotherapy:

• No prior postoperative chemotherapy
• No concurrent anticancer chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior postoperative radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No prior postoperative investigational treatment
• No prior imatinib mesylate (Gleevec; STI571)
• No other concurrent anticancer agents
• No other concurrent investigational drugs
• No concurrent full-dose warfarin for therapeutic anticoagulation (concurrent mini-dose warfarin [1 mg orally per day] for prophylaxis of central venous catheter thrombosis allowed)

Alabama
      Mobile Infirmary Medical Center, Mobile,  Alabama,  36640-0460,  United States; Recruiting
Arkansas
      Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center, Orange,  California,  92868,  United States; Recruiting
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States; Recruiting
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States; Recruiting
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States; Recruiting
Florida
      H. Lee Moffitt Cancer Center and Research Institute at University of South Florida, Tampa,  Florida,  33612-9497,  United States; Recruiting
      Lakeland Regional Cancer Center at Lakeland Regional Medical Center, Lakeland,  Florida,  33804-1057,  United States; Recruiting
      Morton Plant Hospital, Clearwater,  Florida,  33756,  United States; Recruiting
      University of Florida Shands Cancer Center, Gainesville,  Florida,  32610-100277,  United States; Recruiting
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States; Recruiting
Georgia
      Cancer Care and Research Pavilion at St. Joseph's/Candler, Savannah,  Georgia,  31405-6015,  United States; Recruiting
      Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah,  Georgia,  31403-3089,  United States; Recruiting
      Surgical Oncology of Northeast Georgia, Gainesville,  Georgia,  30501,  United States; Recruiting
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States; Recruiting
      Queen's Cancer Institute at Queen's Medical Center, Honolulu,  Hawaii,  96813,  United States; Recruiting
      St. Francis Medical Center, Honolulu,  Hawaii,  96817,  United States; Recruiting
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
      Evanston Northwestern Health Care - Evanston Hospital, Evanston,  Illinois,  60201,  United States; Recruiting
      La Grange Oncology Associates, La Grange,  Illinois,  60525,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202,  United States; Recruiting
Iowa
      Genesis Regional Cancer Center at Genesis Medical Center, Davenport,  Iowa,  52803,  United States; Recruiting
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States; Recruiting
      Central Baptist Hospital, Lexington,  Kentucky,  40503-9985,  United States; Recruiting
      Western Baptist Hospital, Paducah,  Kentucky,  42001,  United States; Recruiting
Maryland
      Alvin and Lois Lapidus Cancer Institute at Sinai Hospital, Baltimore,  Maryland,  21215,  United States; Recruiting
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States; Recruiting
      St. Agnes Cancer Center, Baltimore,  Maryland,  21229,  United States; Recruiting
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States; Recruiting
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
Michigan
      Lacks Cancer Center at Saint Mary's Mercy Medical Center, Grand Rapids,  Michigan,  49503,  United States; Recruiting
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States; Recruiting
      Spectrum Health Downtown Campus, Grand Rapids,  Michigan,  49503,  United States; Recruiting
      Spectrum Health Hospital - Blodgett Campus, Grand Rapids,  Michigan,  49506,  United States; Recruiting
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
Mississippi
      Keesler Medical Center - Keesler Air Force Base, Keesler AFB,  Mississippi,  39534-2576,  United States; Recruiting
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia,  Missouri,  65203,  United States; Recruiting
      Saint Louis University Cancer Center, Saint Louis,  Missouri,  63110-0250,  United States; Recruiting
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110-1093,  United States; Recruiting
New Hampshire
      New Hampshire Oncology-Hematology, PA - Hooksett, Hooksett,  New Hampshire,  03106,  United States; Recruiting
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States; Recruiting
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
      Orange Regional Medical Center - Horton Campus, Middletown,  New York,  10940-4199,  United States; Recruiting
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States; Recruiting
      SUNY Downstate Medical Center, Brooklyn,  New York,  11203,  United States; Recruiting
North Carolina
      Blumenthal Cancer Center at Carolinas Medical Center, Charlotte,  North Carolina,  28232-2861,  United States; Recruiting
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
      Presbyterian Cancer Center at Presbyterian Hospital, Charlotte,  North Carolina,  28233-3549,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting
      Bethesda North Hospital, Cincinnati,  Ohio,  45242,  United States; Recruiting
      Charles F. Kettering Memorial Hospital, Kettering,  Ohio,  45429,  United States; Recruiting
      Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland,  Ohio,  44106-5065,  United States; Recruiting
      Miami Valley Hospital, Dayton,  Ohio,  45409,  United States; Recruiting
      Middletown Regional Hospital, Middletown,  Ohio,  45044-4898,  United States; Recruiting
      Tri-Health Good Samaritan Hospital, Cincinnati,  Ohio,  90027,  United States; Recruiting
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428-1002,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting
Pennsylvania
      Abington Memorial Hospital, Abington,  Pennsylvania,  19001,  United States; Recruiting
      Abramson Cancer Center at the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104-4283,  United States; Recruiting
      John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital, Allentown,  Pennsylvania,  18105-1556,  United States; Recruiting
      Kimmel Cancer Center at Thomas Jefferson University - Philadelphia, Philadelphia,  Pennsylvania,  19107-5541,  United States; Recruiting
      Robert Packer Hospital, Sayre,  Pennsylvania,  18840-1698,  United States; Recruiting
South Carolina
      Hollings Cancer Center at Medical University of South Carolina, Charleston,  South Carolina,  29425,  United States; Recruiting
Tennessee
      Baptist Hospital, Nashville,  Tennessee,  37236,  United States; Recruiting
      Dan Rudy Cancer Center at Saint Thomas Hospital, Nashville,  Tennessee,  37202-0000,  United States; Recruiting
      Danville Radiation Therapy Center, Memphis,  Tennessee,  38104,  United States; Recruiting
      Sarah Cannon Cancer Center at Parkridge Medical Center, Chattanooga,  Tennessee,  37404-3285,  United States; Recruiting
      University of Tennessee Cancer Institute at Methodist Central Hospital, Memphis,  Tennessee,  38104,  United States; Recruiting
      University Surgical Associates, Chattanooga,  Tennessee,  37404,  United States; Recruiting
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6860,  United States; Recruiting
Texas
      Harrington Cancer Center, Amarillo,  Texas,  79106,  United States; Recruiting
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting
      Presbyterian Hospital of Dallas, Dallas,  Texas,  75231,  United States; Recruiting
      University of Texas Medical Branch, Galveston,  Texas,  77555-0527,  United States; Recruiting
      Veterans Affairs Medical Center - Amarillo, Amarillo,  Texas,  79106,  United States; Recruiting
Utah
      Dixie Regional Medical Center, Saint George,  Utah,  84770,  United States; Recruiting
      Huntsman Cancer Institute at University of Utah, Salt Lake City,  Utah,  84112,  United States; Recruiting
      McKay-Dee Hospital Center, Ogden,  Utah,  84403,  United States; Recruiting
      Utah Valley Regional Medical Center - Provo, Provo,  Utah,  84604,  United States; Recruiting
Washington
      University Cancer Center at University of Washington Medical Center, Seattle,  Washington,  98195-6043,  United States; Recruiting
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States; Recruiting
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States; Recruiting
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States; Recruiting
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-7375,  United States; Recruiting
Canada, Ontario
      Mount Sinai Hospital - Toronto, Toronto,  Ontario,  M5G 1X5,  Canada; Recruiting

Study chairs or principal investigators

Ronald DeMatteo, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   
Martin E. Blackstein, MD,  Study Chair,  Mount Sinai Hospital - Toronto   
Christopher W. Ryan, MD,  Study Chair,  University of Chicago Cancer Research Center   
John T. Vetto, MD,  Study Chair,  Oregon Health and Science University   

Study ID Numbers:  CDR0000069452; ACOSOG-Z9001; CAN-NCIC-SRC1; CALGB-ACOSOG-Z9001; SWOG-ACOSOG-Z9001; NCT00041197
Record last reviewed:  February 2005
Last Updated:  March 28, 2005
Record first received:  July 8, 2002
ClinicalTrials.gov Identifier:  NCT00041197
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08