Clinical trial NCT00009906: Comparison of Two Different Doses of STI571 in Treating Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Gastrointestinal Stromal Tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Eastern Cooperative Oncology Group
name: SWOG Cancer Research Network
name: NCIC Clinical Trials Group
First posted: 2004-02-03
Enrollment: 748
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival (OS)
timeFrame: Up to 3 years
measure: Progression-free survival
timeFrame: From date of registration to date of first observation of progressive disease or death due to any cause, assessed up to 3 years
measure: 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
timeFrame: Up to 3 year after completion of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Western Regional CCOP
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Health Sciences Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology Group-Rogers
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Long Beach
country: United States
facility: Long Beach Community Hospital
state: California
city: Los Angeles
country: United States
facility: University of Southern California/Norris Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles Health System
state: California
city: Novato
country: United States
facility: Sutter Cancer Research Consortium
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente - Sacramento
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mount Zion
state: California
city: Sana Rosa
country: United States
facility: Santa Rosa Memorial Hospital
state: California
city: Stanford
country: United States
facility: Stanford University Hospitals and Clinics
state: California
city: Denver
country: United States
facility: Presbyterian - Saint Lukes Medical Center - Health One
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Pueblo
country: United States
facility: Saint Mary Corwin Medical Center
state: Colorado
city: Middletown
country: United States
facility: Middlesex Hospital
state: Connecticut
city: Washington
country: United States
facility: MedStar Oncology Network
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Lake Worth
country: United States
facility: Hematology Oncology Associates
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Orlando
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Albany
country: United States
facility: Phoebe Putney Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Regional CCOP
state: Georgia
city: Macon
country: United States
facility: Medical Center of Central Georgia
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Chicago
country: United States
facility: Hematology and Oncology Associates
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Jesse Brown Veterans Affairs Medical Center
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Decatur
country: United States
facility: Central Illinois CCOP
state: Illinois
city: Elk Grove Village
country: United States
facility: Alexian Brothers Medical and Cancer Center
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Normal
country: United States
facility: Mid-Illinois Hematology Oncology Associates
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital.
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: IU Health Methodist Hospital
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic PC-William R Bliss Cancer Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Prairie Village
country: United States
facility: Kansas City CCOP
state: Kansas
city: Topeka
country: United States
facility: Stormont-Vail Regional Health Center
state: Kansas
city: Ashland
country: United States
facility: Our Lady Bellefonte Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Louisiana State University Health Science Center
state: Louisiana
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Cancer Research Consortium Community Clinical Oncology Program
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan University Hospital
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Hospital and Medical Center
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Grand Rapids Clinical Oncology Program
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Marquette
country: United States
facility: Marquette General Hospital
state: Michigan
city: Fridley
country: United States
facility: Unity Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center-Fairview
state: Minnesota
city: Robbinsdale
country: United States
facility: North Memorial Medical Health Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Clinic - Saint Louis Park
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Charles
country: United States
facility: Saint Joseph's Health Center
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis Cancer and Breast Institute-South City
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Springfield
country: United States
facility: Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield
state: Missouri
city: Omaha
country: United States
facility: Alegent Health Immanuel Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical CCOP
state: New Jersey
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Southeast Cancer Control Consortium CCOP
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Fargo
country: United States
facility: Roger Maris Cancer Center
state: North Dakota
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Columbus CCOP
state: Ohio
city: Dayton
country: United States
facility: Dayton CCOP
state: Ohio
city: Lima
country: United States
facility: Saint Rita's Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Klamath Falls
country: United States
facility: Sky Lakes Medical Center - Cancer Treatment Center
state: Oregon
city: Portland
country: United States
facility: Western Oncology Research Consortium
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Salem
country: United States
facility: Salem Hospital
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Darby
country: United States
facility: Mercy Fitzgerald Hospital
state: Pennsylvania
city: Drexel Hill
country: United States
facility: Delaware County Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Aria Health-Torresdale Campus
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Spartanburg
country: United States
facility: Upstate Carolina CCOP
state: South Carolina
city: Memphis
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Memphis
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Barre
country: United States
facility: Central Vermont Medical Center
state: Vermont
city: Berlin
country: United States
facility: Central Vermont Medical Center/National Life Cancer Treatment
state: Vermont
city: Rutland
country: United States
facility: Rutland Regional Medical Center
state: Vermont
city: Hampton
country: United States
facility: Virginia Oncology Associates-Hampton
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason CCOP
state: Washington
city: Seattle
country: United States
facility: Group Health
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: Tacoma
country: United States
facility: Northwest CCOP
state: Washington
city: Green Bay
country: United States
facility: Saint Vincent Hospital
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton and District Urology Association McMaster Institute
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Health Research Institute-General Division
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
city: San Juan
country: Puerto Rico
facility: San Juan Veterans Affairs Medical Center
city: San Juan
country: Puerto Rico
facility: San Juan City Hospital
Study officials:
affiliation: SWOG Cancer Research Network
name: George Demetri
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.