Imatinib Mesylate in Treating Patients With Primary Gastrointestinal Stromal Tumor That Has Been Completely Removed By Surgery

July 15, 2013 updated by: National Cancer Institute (NCI)

A Phase III Randomized Double-Blind Study of Adjuvant STI571 (Gleevec™) Versus Placebo in Patients Following the Resection of Primary Gastrointestinal Stromal Tumor (GIST)

This randomized phase III trial is studying imatinib mesylate to see how well it works compared to placebo in treating patients with primary gastrointestinal stromal tumor that has been completely removed by surgery. Imatinib mesylate 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether patients with resected primary gastrointestinal stromal tumor (GIST) who are randomized to the STI571 (imatinib mesylate) Arm have longer recurrence-free survival as compared to the patients randomized to the placebo Arm.

SECONDARY OBJECTIVES:

I. To ascertain whether patients with resected primary GIST who are randomized to the STI571 Arm have longer survival as compared to the patients randomized to the placebo Arm.

II. To obtain from patients with GIST: tumor tissue (before therapy with STI571 and if the patient develops recurrence), blood specimens (before therapy with STI571), and serum specimens (before therapy with STI571, after completing therapy with STI571, and if the patient develops recurrence) for scientific correlative analyses.

III. To assess the safety/efficacy of oral STI571 therapy in the adjuvant setting.

OUTLINE: 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, then every 6 months for 10 years.

Study Type

Interventional

Enrollment (Actual)

732

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • American College of Surgeons Oncology Group

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

Inclusion Criteria:

  • Patient must have an ECOG/Zubrod performance status of =< 2
  • Patient must have a histologic diagnosis of primary GIST (without peritoneal or distant metastasis) that expresses Kit protein by immunohistochemistry and have tumor size >= 3cm in maximum dimension
  • Patient must have undergone complete gross resection (includes R0 [negative microscopic margins] and R1 [positive microscopic margins]) of a primary GIST within 70 days prior to registration
  • Patient must have a chest x-ray completed within 28 days prior to registration; NOTE: Chest CT within 28 days prior to registration can be used in lieu of chest x-ray
  • Patient must have a post-operative CT scan with IV and PO contrast or MRI with contrast (if allergic to CT contrast) of abdomen and pelvis within 28 days prior to registration
  • Creatinine =< 1.5 times the institution ULN
  • WBC >= 2,000/mm^3
  • Platelets >= 100,000/mm^3
  • Total Bilirubin =< 1.5 times the institution ULN; NOTE: Patients with elevated bilirubin secondary to Gilbert's disease are eligible to participate in the study
  • AST =< 2.5 times the institution ULN
  • ALT =< 2.5 times the institution ULN
  • Female of childbearing potential must have negative serum pregnancy test; NOTE: Post-menopausal women must be amenorrheic for at least 12 months to be deemed not of reproductive potential
  • Patient or the patient's legally acceptable representative must provide a signed and dated written informed consent prior to registration and any study-related procedures
  • Patient must provide written authorization to allow the use and disclosure of their protected health information; NOTE: This may be obtained in either the study-specific informed consent or in a separate authorization form and must be obtained from the patient prior to study registration (non-US sites are exempt from HIPAA regulations)

  • If patient is a cancer survivor, ALL of the following criteria apply:

    • Patient has undergone potentially curative therapy for all prior malignancies
    • No evidence of any prior malignancies for at least 5 years with no evidence of recurrence (except for effectively treated basal cell or squamous carcinoma of the skin, carcinoma in-situ of the cervix that has been effectively treated by surgery alone, or lobular carcinoma in-situ of the ipsilateral or contralateral breast treated by surgery alone)
    • Patient is deemed by their treating physician to be at low risk for recurrence from prior malignancies

Exclusion Criteria:

  • Patient has received post-operative chemotherapy
  • Patient has received post-operative radiation therapy
  • Patient has received post-operative investigational treatment
  • Patient has received prior therapy with STI571
  • Patient has had an active infection requiring antibiotics within 14 days prior to registration
  • Patient has objective evidence of residual disease on the postoperative CT scan or MRI of the abdomen or pelvis
  • Patient, if female and breastfeeding; NOTE: It is not known whether STI571or its metabolites are excreted in human milk; however, in lactating female rats administered 100mg/kg, a dose approximately equal to the maximum clinical dose of 800mg/day based on body surface area, STI571 and /or its metabolites were extensively excreted in milk; it is estimated that approximately 1.5% of a maternal dose is excreted into milk, which is equivalent to a dose to the infant of 30% the maternal dose per unit body weight; women should be advised against breastfeeding while taking STI571
  • Patient has New York Heart Association class 3 or 4 cardiac disease
  • Patient is taking full dose warfarin; NOTE: The use of mini-dose warfarin (1mg orally per day) for prevention of central line-associated deep venous thrombosis is permitted

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: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I (imatinib mesylate)
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.
Other: laboratory biomarker analysis
Correlative studies
Drug: imatinib mesylate
Given orally (PO)
Other Names:
  • Gleevec
  • CGP 57148
  • Glivec
Placebo Comparator: Arm II (placebo)
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.
Other: laboratory biomarker analysis
Correlative studies
Other: placebo
Given PO
Other Names:
  • PLCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence-free survival (RFS)
Time Frame: From date of resection to the date of first observation of recurrence, assessed up to 10 years
An O'Brien-Fleming bound will be used to stop the trial early for superiority of the STI571 arm.
From date of resection to the date of first observation of recurrence, assessed up to 10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time Frame: Up to 5 years
Safety analysis will consist of routine tabulations, detailed documentation concerning all adverse events, detailed documentation of any unusual events, and any special reports, analyses, or tabulations requested by the DSMC.
Up to 5 years
Relationship between genetic and phenotypic characteristics of GIST and clinical outcomes
Time Frame: Up to 10 years
Up to 10 years

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Ronald DeMatteo, American College of Surgeons

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

June 1, 2002

Primary Completion (Actual)

April 1, 2007

Study Registration Dates

First Submitted

July 8, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

July 16, 2013

Last Update Submitted That Met QC Criteria

July 15, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02930
  • U10CA076001 (U.S. NIH Grant/Contract)
  • Z9001
  • CDR0000069452

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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