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Imatinib Mesylate (Gleevec; STI571) in Treating Patients With Primary Gastrointestinal Stromal Tumor That Has Been Completely Removed by Surgery
This study is ongoing, but not recruiting participants.
First Received: July 8, 2002   Last Updated: April 18, 2009   History of Changes
Sponsor: American College of Surgeons
Collaborators: National Cancer Institute (NCI)
NCIC Clinical Trials Group
Cancer and Leukemia Group B
Southwest Oncology Group
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00041197
  Purpose

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 Intervention Phase
Gastrointestinal Stromal Tumor
Drug: imatinib mesylate
Other: placebo
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control
Official Title: A Phase III Randomized Double-Blind Study of Adjuvant STI571 (Gleevec) Versus Placebo in Patients Following the Resection of Primary GastroIntestinal Stromal Tumor (GIST)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Recurrence-free survival as measured by serial CT scans at 3-6 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival as measured by serial doctor visits at 3-6 months [ Designated as safety issue: No ]

Estimated Enrollment: 732
Study Start Date: June 2002
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Experimental
Patients receive oral imatinib mesylate (Gleevec; STI571) once daily for 1 year.
Drug: imatinib mesylate
Given orally
Arm II: Placebo Comparator
Patients receive oral placebo once daily for 1 year.
Other: placebo
Given orally

Detailed Description:

OBJECTIVES:

Primary

  • Compare the recurrence-free survival of patients with resected primary gastrointestinal stromal tumor treated with adjuvant imatinib mesylate (Gleevec; STI571) vs placebo.

Secondary

  • Compare the overall survival of patients treated with these regimens.
  • 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 732 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00041197

  Hide Study Locations
Locations
United States, Alaska
Providence Cancer Center
Anchorage, Alaska, United States, 99508
United States, California
Kaiser Foundation Hospital - San Rafael
San Rafael, California, United States, 94903
Kaiser Permanente - Fremont
Fremont, California, United States, 94538
Kaiser Permanente Medical Center - Hayward
Hayward, California, United States, 94545
Kaiser Permanente Medical Center - Oakland
Oakland, California, United States, 94611
Kaiser Permanente Medical Center - Redwood City
Redwood City, California, United States, 94063
Kaiser Permanente Medical Center - Richmond
Richmond, California, United States, 94801
Kaiser Permanente Medical Center - South San Francisco
South San Francisco, California, United States, 94080
Kaiser Permanente Medical Center - Sacramento
Sacramento, California, United States, 95825
Kaiser Permanente Medical Center - San Francisco Geary Campus
San Francisco, California, United States, 94115
Kaiser Permanente Medical Center - Santa Clara Kiely Campus
Santa Clara, California, United States, 95051
Kaiser Permanente Medical Center - Santa Rosa
Santa Rosa, California, United States, 95403
Kaiser Permanente Medical Center - Santa Teresa
San Jose, California, United States, 95119
Kaiser Permanente Medical Center - Roseville
Roseville, California, United States, 95661
Kaiser Permanente Medical Center - Vallejo
Vallejo, California, United States, 94589
Kaiser Permanente Medical Center - Walnut Creek
Walnut Creek, California, United States, 94596
Kaiser Permanente Medical Facility - Stockton
Stockton, California, United States, 95210
South Sacramento Kaiser-Permanente Medical Center
Sacramento, California, United States, 95823
United States, Georgia
Gwinnett Medical Center
Lawrenceville, Georgia, United States, 30045
Charles B. Eberhart Cancer Center at DeKalb Medical Center
Decatur, Georgia, United States, 30033
CCOP - Atlanta Regional
Atlanta, Georgia, United States, 30342
Saint Joseph's Hospital of Atlanta
Atlanta, Georgia, United States, 30342-1701
Southern Regional Medical Center
Riverdale, Georgia, United States, 30274-2600
United States, Illinois
Edward Hospital Cancer Center
Naperville, Illinois, United States, 60540
Resurrection Medical Center
Chicago, Illinois, United States, 60631
United States, Iowa
Genesis Regional Cancer Center at Genesis Medical Center
Davenport, Iowa, United States, 52803
Genesis Medical Center - West Campus
Davenport, Iowa, United States, 52804
Covenant Cancer Treatment Center
Waterloo, Iowa, United States, 50702
United States, Michigan
Oncology Care Associates, PLLC
Saint Joseph, Michigan, United States, 49085
United States, Minnesota
Willmar Cancer Center at Rice Memorial Hospital
Willmar, Minnesota, United States, 56201
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805
United States, New Jersey
Frederick R. and Betty M. Smith Cancer Treatment Center
Sparta, New Jersey, United States, 07871
United States, New York
Tucker Center for Cancer Care at Orange Regional Medical Center
Middletown, New York, United States, 10940-4199
United States, North Carolina
Forsyth Regional Cancer Center at Forsyth Medical Center
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Adena Regional Medical Center
Chillicothe, Ohio, United States, 45601
CCOP - Columbus
Columbus, Ohio, United States, 43215
Genesis - Good Samaritan Hospital
Zanesville, Ohio, United States, 43701
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Community Hospital of Springfield and Clark County
Springfield, Ohio, United States, 45505
Community Oncology Group at Cleveland Clinic Cancer Center
Independence, Ohio, United States, 44131
Doctors Hospital at Ohio Health
Columbus, Ohio, United States, 43228
Fairfield Medical Center
Lancaster, Ohio, United States, 43130
Cleveland Clinic - Wooster
Wooster, Ohio, United States, 44691
Good Samaritan Hospital Cancer Treatment Center
Cincinnati, Ohio, United States, 45220
Grady Memorial Hospital
Delaware, Ohio, United States, 43015
Grant Riverside Cancer Services
Columbus, Ohio, United States, 43215
Licking Memorial Cancer Care Program at Licking Memorial Hospital
Newark, Ohio, United States, 43055
Mount Carmel St. Ann's Cancer Center
Westerville, Ohio, United States, 43081
Mount Carmel Health - West Hospital
Columbus, Ohio, United States, 43222
Mercy Medical Center
Springfield, Ohio, United States, 45504
Riverside Methodist Hospital Cancer Care
Columbus, Ohio, United States, 43214-3998
Strecker Cancer Center at Marietta Memorial Hospital
Marietta, Ohio, United States, 45750
United States, Pennsylvania
Frankford Hospital Cancer Center - Torresdale Campus
Philadelphia, Pennsylvania, United States, 19114
Hematology and Oncology Associates of Northeastern Pennsylvania
Scranton, Pennsylvania, United States, 18510
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
Philadelphia, Pennsylvania, United States, 19107-5541
United States, Vermont
Fletcher Allen Health Care - University Health Center Campus
Burlington, Vermont, United States, 05401
Mountainview Medical
Berlin, Vermont, United States, 05602
Sponsors and Collaborators
American College of Surgeons
NCIC Clinical Trials Group
Cancer and Leukemia Group B
Southwest Oncology Group
Investigators
Study Chair: Ronald DeMatteo, MD Memorial Sloan-Kettering Cancer Center
Study Chair: Martin E. Blackstein, MD Mount Sinai Hospital - Toronto
Study Chair: Christopher W. Ryan, MD University of Chicago
Study Chair: John T. Vetto, MD, FACS OHSU Knight Cancer Institute
  More Information

Additional Information:
Publications:
Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K; American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Mar 28;373(9669):1097-104. Epub 2009 Mar 18.
DeMatteo R, Owzar K, Maki R, et al.: Adjuvant imatinib mesylate increases recurrence free survival (RFS) in patients with completely resected localized primary gastrointestinal stromal tumor (GIST): North American Intergroup phase III trial ACOSOG Z9001. [Abstract] J Clin Oncol 25 (Suppl 18):A-10079, 2007.
ACOSOG Z9001: a phase III randomized double-blind study of adjuvant imatinib mesylate versus placebo in patients following the resection of primary gastrointestinal stromal tumor. Clin Adv Hematol Oncol 2 (5): 310.
Hillman SL, Sargent DJ, Bot, BM, et al.: Questionable value of attribution when interpreting adverse event data: a joint evaluation by North Central Cancer Treatment Group (NCCTG) and American College of Surgeons Oncology Group (ACOSOG). [Abstract] J Clin Oncol 25 (Suppl 18): A-6511, 324s, 2007.

Responsible Party: American College of Surgeons Oncology Group ( David M. Ota )
Study ID Numbers: CDR0000069452, ACOSOG-Z9001, CAN-NCIC-SRC1, CALGB-ACOSOG-Z9001, SWOG-ACOSOG-Z9001, UWCC-UW-6303, UWCC-UW-03-8438-A-03
Study First Received: July 8, 2002
Last Updated: April 18, 2009
ClinicalTrials.gov Identifier: NCT00041197     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
gastrointestinal stromal tumor

Additional relevant MeSH terms:
Digestive System Neoplasms
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Antineoplastic Agents
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions
Imatinib
Neoplasms
Neoplasms by Site
Digestive System Diseases
Therapeutic Uses
Gastrointestinal Neoplasms
Gastrointestinal Stromal Tumors

ClinicalTrials.gov processed this record on November 30, 2009