Comparison of Two Different Doses of STI571 in Treating Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor

Phase III Randomized, Intergroup Trial Assessing the Clinical Activity Of STI-571 at Two Dose Levels in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors (GIST) Expressing the Kit Receptor Tyrosine Kinase (CD117)

Randomized phase III trial to compare the effectiveness of two different doses of STI571 in treating patients who have metastatic or unresectable gastrointestinal stromal tumor. STI571 may interfere with the growth of tumor cells and may be an effective treatment for cancer. It is not yet known which dose of STI571 is more effective in treating gastrointestinal stromal tumors.

Study Overview

• Status: Terminated
• Conditions: Gastrointestinal Stromal Tumor
• Intervention / Treatment: Drug: Imatinib Mesylate

Detailed Description

PRIMARY OBJECTIVES:

I. Compare the overall and progression-free survival of patients with CD117-expressing metastatic or unresectable gastrointestinal stromal tumor treated with two different doses of imatinib mesylate.

II. Compare the confirmed, unconfirmed, complete, and partial response rates in patients treated with these regimens.

III. Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms.

Arm I: Patients receive oral imatinib mesylate once daily.

Arm II: Patients receive oral imatinib mesylate twice daily.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients in arm I with progressive disease may cross over to arm II and receive treatment in the absence of further disease progression.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study within 24 months.

• Study Type: Interventional
• Enrollment (Actual): 748
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA-Vancouver Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Hamilton, Ontario, Canada, L8N 4A6
      • Hamilton and District Urology Association McMaster Institute
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Ottawa, Ontario, Canada, K1H 1C4
      • Ottawa Health Research Institute-General Division
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University Department of Oncology
• Puerto Rico
  • San Juan, Puerto Rico, 00936
    • San Juan City Hospital
  • San Juan, Puerto Rico, 00921-3201
    • San Juan Veterans Affairs Medical Center
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Western Regional CCOP
    • Tucson, Arizona, United States, 85724
      • University of Arizona Health Sciences Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
    • Rogers, Arkansas, United States, 72758
      • Highlands Oncology Group-Rogers
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Long Beach, California, United States, 90804
      • Long Beach Community Hospital
    • Los Angeles, California, United States, 90033
      • University of Southern California/Norris Cancer Center
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles Health System
    • Novato, California, United States, 94945
      • Sutter Cancer Research Consortium
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • Sacramento, California, United States, 95825
      • Kaiser Permanente - Sacramento
    • San Diego, California, United States, 92103
      • University of California San Diego
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • Sana Rosa, California, United States, 95405
      • Santa Rosa Memorial Hospital
    • Stanford, California, United States, 94305
      • Stanford University Hospitals and Clinics
  • Colorado
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
  • Connecticut
    • Middletown, Connecticut, United States, 06457
      • Middlesex Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Oncology Network
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Lake Worth, Florida, United States, 33461
      • Hematology Oncology Associates
    • Orlando, Florida, United States, 32803
      • Florida Hospital Orlando
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Albany, Georgia, United States, 31701
      • Phoebe Putney Memorial Hospital
    • Atlanta, Georgia, United States, 30322
      • Emory University/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30342
      • Atlanta Regional CCOP
    • Macon, Georgia, United States, 31208
      • Medical Center of Central Georgia
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60611
      • Hematology and Oncology Associates
    • Chicago, Illinois, United States, 60612
      • Jesse Brown Veterans Affairs Medical Center
    • Decatur, Illinois, United States, 62526
      • Central Illinois CCOP
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Medical and Cancer Center
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Normal, Illinois, United States, 61761
      • Mid-Illinois Hematology Oncology Associates
    • Park Ridge, Illinois, United States, 60068
      • Advocate Lutheran General Hospital.
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • IU Health Methodist Hospital
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC-William R Bliss Cancer Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Prairie Village, Kansas, United States, 66208
      • Kansas City CCOP
    • Topeka, Kansas, United States, 66604
      • Stormont-Vail Regional Health Center
  • Kentucky
    • Ashland, Kentucky, United States, 41101
      • Our Lady Bellefonte Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Science Center
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium Community Clinical Oncology Program
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan University Hospital
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital and Medical Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids Clinical Oncology Program
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Marquette, Michigan, United States, 49855
      • Marquette General Hospital
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center-Fairview
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • Saint Joseph's Health Center
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63109
      • Saint Louis Cancer and Breast Institute-South City
    • Springfield, Missouri, United States, 65804
      • Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield
  • Nebraska
    • Omaha, Nebraska, United States, 68122
      • Alegent Health Immanuel Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical CCOP
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College of Medicine
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center - Moses Campus
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
    • Winston-Salem, North Carolina, United States, 27104
      • Southeast Cancer Control Consortium CCOP
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Roger Maris Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43215
      • Columbus CCOP
    • Dayton, Ohio, United States, 45420
      • Dayton CCOP
    • Lima, Ohio, United States, 45801
      • Saint Rita's Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Klamath Falls, Oregon, United States, 97601
      • Sky Lakes Medical Center - Cancer Treatment Center
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97213
      • Western Oncology Research Consortium
    • Salem, Oregon, United States, 97301
      • Salem Hospital
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Darby, Pennsylvania, United States, 19023-1291
      • Mercy Fitzgerald Hospital
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • Philadelphia, Pennsylvania, United States, 19114
      • Aria Health-Torresdale Campus
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Upstate Carolina CCOP
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Baptist Memorial Hospital and Cancer Center-Memphis
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Vermont
    • Barre, Vermont, United States, 05641
      • Central Vermont Medical Center
    • Berlin, Vermont, United States, 05602
      • Central Vermont Medical Center/National Life Cancer Treatment
    • Rutland, Vermont, United States, 05701
      • Rutland Regional Medical Center
  • Virginia
    • Hampton, Virginia, United States, 23666
      • Virginia Oncology Associates-Hampton
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason CCOP
    • Seattle, Washington, United States, 98109
      • Group Health
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Tacoma, Washington, United States, 98405
      • Northwest CCOP
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient must have a biopsy proven diagnosis of gastrointestinal stromal tumor (GIST) which is distantly metastatic or unresectable; tumors must meet BOTH of the following criteria:

  • The primary must be of visceral or intra-abdominal origin
  • All patients must have immunohistochemical documentation of KIT (CD117) expression by tumor documented by DAKO antibody staining for suggested methodology) Material must be submitted to the CALGB Pathology Coordinating Center for pathology review; it is strongly recommended that snap-frozen tissue biopsy and sera be stored for future submission whenever possible
• Patient must have measurable or non-measurable disease by conventional scan imaging (CT or MRI) or physical examination; tests used to assess disease must have been performed within 28 days prior to registration; if a target lesion has been previously embolized or irradiated, there must be objective evidence of progression to be considered for response assessment
• Patient must have an identified team (including a medical oncologist and a surgeon) to provide care
• Patient must not have known brain metastasis
• Patient must have a Zubrod performance status of 0 - 3
• Patient must have resolution of transient toxicities from any prior therapy to =< grade 1 (NCI-CTC version 2.0)
• The patient must not have received chemotherapy, biologic therapy or any other investigational drug for any reason within 28 days prior to registration; patients must not have had a major surgery within 14 days prior to registration

• If day 14 or 28 falls on a weekend or holiday, the limit may be extended to the next working day

  • In calculating days of tests and measurements, the day a test or measurement is done is considered day 0; therefore, if a test is done on a Monday, the Monday two weeks later would be considered day 14; this allows for efficient patient scheduling without exceeding the guidelines
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
• Patients on lower dose arm (Arm 1) will be allowed to increase the daily dose of STI-571 in the case of disease progression; if there is questionable disease progression, the treating investigator should contact the primary Study Coordinator, Dr. George Demetri at 617/632-3985 to review progression information and discuss treatment options

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (imatinib mesylate); Patients receive oral imatinib mesylate once daily.	Drug: Imatinib Mesylate; Given orally
Experimental: Arm II (imatinib mesylate); Patients receive oral imatinib mesylate twice daily.	Drug: Imatinib Mesylate; Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	Up to 3 years
Progression-free survival	From date of registration to date of first observation of progressive disease or death due to any cause, assessed up to 3 years
Toxicity defined as any grade 3 or greater organ toxicity, or any grade 4 or greater hematological toxicity as assessed by CTCAE version 2.0	Up to 3 year after completion of treatment

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Eastern Cooperative Oncology Group; NCIC Clinical Trials Group; Southwest Oncology Group
• Investigators: Principal Investigator: George Demetri, Southwest Oncology Group

Publications and helpful links

General Publications

• Heinrich MC, Rankin C, Blanke CD, Demetri GD, Borden EC, Ryan CW, von Mehren M, Blackstein ME, Priebat DA, Tap WD, Maki RG, Corless CL, Fletcher JA, Owzar K, Crowley JJ, Benjamin RS, Baker LH. Correlation of Long-term Results of Imatinib in Advanced Gastrointestinal Stromal Tumors With Next-Generation Sequencing Results: Analysis of Phase 3 SWOG Intergroup Trial S0033. JAMA Oncol. 2017 Jul 1;3(7):944-952. doi: 10.1001/jamaoncol.2016.6728. Erratum In: JAMA Oncol. 2017 Jul 1;3(7):1002.

Study record dates

Study Major Dates

• Study Start: December 1, 2000
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: February 2, 2001
• First Submitted That Met QC Criteria: February 2, 2004
• First Posted (Estimate): February 3, 2004

Study Record Updates

• Last Update Posted (Estimate): December 23, 2014
• Last Update Submitted That Met QC Criteria: December 19, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: NCI-2012-02372 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM17003 (U.S. NIH Grant/Contract); U10CA032102 (U.S. NIH Grant/Contract); U10CA180888 (U.S. NIH Grant/Contract); S0033 (Other Identifier: CTEP); INT-S0033; CDR0000068422; CAN-NCIC-S0033; CLB-80004; SWOG-S0033; E-S0033