Imatinib Mesylate in Treating Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumor

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Italian Sarcoma Group
Australasian Gastro-Intestinal Trials Group
Scandinavian Sarcoma Group
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00685828
First received: May 22, 2008
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known which dose of imatinib mesylate is more effective in treating gastrointestinal stromal tumor.

PURPOSE: This randomized phase III trial is studying two different doses of imatinib mesylate to compare how well they work in treating patients with unresectable or metastatic gastrointestinal stromal tumor.


Condition Intervention Phase
Gastrointestinal Stromal Tumor
Drug: imatinib mesylate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Randomized, Intergroup, International 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)

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Objective tumor response [ Designated as safety issue: No ]
  • Toxicity as assessed by NCI CTC v2.0 [ Designated as safety issue: Yes ]

Enrollment: 946
Study Start Date: January 2001
Primary Completion Date: February 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients receive low-dose oral imatinib mesylate once daily in the absence of disease progression or unacceptable toxicity.
Drug: imatinib mesylate
By mouth
Experimental: Arm II
Patients receive high-dose oral imatinib mesylate twice daily in the absence of disease progression or unacceptable toxicity.
Drug: imatinib mesylate
By mouth

Detailed Description:

OBJECTIVES:

Primary

  • To compare outcomes of patients with unresectable or metastatic gastrointestinal stromal tumor that expresses KIT (CD117) treated with low-dose imatinib mesylate vs high-dose imatinib mesylate.

Secondary

  • To assess response rates in patients treated with two different doses of imatinib mesylate.
  • To assess the toxicities of two different doses of imatinib mesylate in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, measurability of disease (measurable vs non-measurable), and WHO performance status (0-2 vs 3). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive low-dose oral imatinib mesylate once daily in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive high-dose oral imatinib mesylate twice daily in the absence of disease progression or unacceptable toxicity.

In the event of disease progression, patients on arm I may cross over to arm II and receive high-dose imatinib mesylate. Patients who continue to progress despite treatment with high-dose imatinib mesylate are removed from the study.

After completion of study therapy, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed gastrointestinal stromal tumor (GIST)

    • Metastatic or unresectable disease
  • Immunohistochemical confirmation of KIT (CD117) expression by tumor as documented by DAKO antibody staining
  • Measurable or non-measurable disease by conventional imaging (CT scan or MRI) or physical examination

    • If a target lesion has been previously embolized or irradiated, there must be objective evidence of progression to be considered for response assessment
  • No known brain metastasis

PATIENT CHARACTERISTICS:

  • WHO performance status 0-3
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN if hepatic metastases are present)
  • Creatinine ≤ 1.5 times ULN
  • ANC ≥ 1,000/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9 g/dL (transfusions allowed)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for up to 3 months after completion of study therapy
  • No NYHA class III-IV cardiac disease
  • No congestive heart failure or myocardial infarction within the past 2 months
  • No severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, or active uncontrolled infection [e.g., HIV])
  • No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, 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
  • No medical, psychological, familial, sociological, or geographical condition that, in the opinion of the investigator, may preclude the patient's ability to tolerate or complete study treatment, comply with study protocol and follow-up schedule, or give reliable informed consent

PRIOR CONCURRENT THERAPY:

  • Recovered from all prior therapy
  • More than 28 days since prior chemotherapy, biologic therapy, or any other investigational drug
  • More than 14 days since prior major surgery
  • No concurrent therapeutic anticoagulation with coumarin derivatives

    • Concurrent therapeutic anticoagulation with low-molecular weight heparin allowed
    • Concurrent mini-dose coumarin derivatives (i.e., equivalent to 1 mg of oral warfarin daily) as prophylaxis allowed
  • No concurrent cytokines (i.e., filgrastim [G-CSF] or sargramostim [GM-CSF]) to support blood counts
  • No other concurrent investigational drugs
  • No other concurrent anticancer agents, including chemotherapy, radiotherapy, or anticancer biologic therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00685828

Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Italian Sarcoma Group
Australasian Gastro-Intestinal Trials Group
Scandinavian Sarcoma Group
Investigators
Study Chair: Jacob Verweij, MD, PhD Daniel Den Hoed Cancer Center at Erasmus Medical Center
Study Chair: Paolo G. Casali, MD Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Study Chair: John R. Zalcberg, MB, BS, PhD, FRACP Peter MacCallum Cancer Centre, Australia
Study Chair: Kirsten Sundby Hall, MD Lund University Hospital
  More Information

Additional Information:
Publications:
Verweij J, Casali PG, Zalcberg J, et al.: Early efficacy comparison of two doses of imatinib for the treatment of advanced gastro-intestinal stromal tumors (GIST): interim results of a randomized phase III trial from the EORTC-STBSG, ISG and AGITG. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-3272, 814, 2003.
van Glabbeke MM, Owzar K, Rankin C, et al.: Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST): a meta-analyis based on 1,640 patients (pts). [Abstract] J Clin Oncol 25 (Suppl 18): A-10004, 546s, 2007.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00685828     History of Changes
Other Study ID Numbers: EORTC-62005, EORTC-62005, AGITG-AGO102-GIST, ISG-62005, SSG-15
Study First Received: May 22, 2008
Last Updated: July 3, 2014
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
gastrointestinal stromal tumor

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Neoplasms
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014