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

July 3, 2014 updated by: European Organisation for Research and Treatment of Cancer - EORTC

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)

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

946

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Progression-free survival

Secondary Outcome Measures

Outcome Measure
Overall survival
Objective tumor response
Toxicity as assessed by NCI CTC v2.0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Collaborators

Australasian Gastro-Intestinal Trials Group
Italian Sarcoma 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2001

Primary Completion (Actual)

February 1, 2002

Study Registration Dates

First Submitted

May 22, 2008

First Submitted That Met QC Criteria

May 23, 2008

First Posted (Estimate)

May 28, 2008

Study Record Updates

Last Update Posted (Estimate)

July 4, 2014

Last Update Submitted That Met QC Criteria

July 3, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-62005
  • AGITG-AGO102-GIST
  • ISG-62005
  • SSG-15

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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