Imatinib Mesylate or Observation Only in Treating Patients Who Have Undergone Surgery for Localized Gastrointestinal Stromal Tumor

July 6, 2018 updated by: European Organisation for Research and Treatment of Cancer - EORTC

Intermediate and High Risk Localized, Completely Resected, Gastrointestinal Stromal Tumors (GIST) Expressing KIT Receptor: A Controlled Randomized Trial on Adjuvant Imatinib Mesylate (Glivec) Versus No Further Therapy After Complete Surgery

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving imatinib mesylate after surgery may kill any remaining tumor cells. It is not yet known whether imatinib mesylate is more effective than observation only in treating gastrointestinal stromal tumor.

PURPOSE: This randomized phase III trial is studying imatinib mesylate to see how well it works compared to observation only in treating patients who have undergone surgery for localized gastrointestinal stromal tumor.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Assess whether there is a difference in overall survival between intermediate and high-risk localized GIST patients undergoing complete surgery alone and those undergoing complete surgery plus adjuvant imatinib mesylate 400 mg daily for two years Secondary
  • Assess whether there is a difference in relapse-free survival and relapse-free interval between GIST undergoing complete surgery alone and those undergoing surgery + adjuvant Imatinib mesylate 400 mg daily for two years.
  • Determine the safety of this drug in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, risk category (high vs intermediate), tumor site (gastric vs other), and resection level (R0 vs R1).

  • Arm I: Patients receive adjuvant oral imatinib mesylate once daily for 2 years in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients are observed (without receiving further antitumoral therapy) every 3 months for 2 years.

After completion of study treatment, patients in arm I are followed every 3 months for 2 years. All patients are then followed every 4 months for 3 years and at least annually thereafter.

PROJECTED ACCRUAL: A total of 900 patients will be accrued for this study within 3.5 years.

Study Type

Interventional

Enrollment (Actual)

908

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

  • Australia
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Flinders Medical Centre
  • Denmark
      • Herlev, Denmark, DK-2730
        • Herlev University Hospital
  • France
      • Abbeville, France, 80101
        • Centre Hospitalier d'Abbeville
      • Angers, France, 49036
        • Centre Paul Papin
      • Besancon, France, 25030
        • Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
      • Bobigny, France, 93009
        • Hôpital Avicenne
      • Bordeaux, France, 33076
        • Institut Bergonie
      • Boulogne Billancourt, France, 92100
        • Hopital Ambroise Pare
      • Brest, France, 29200
        • C.H.U. de Brest
      • Caen, France, 14076
        • Centre Regional Francois Baclesse
      • Clermont-Ferrand, France, 63011
        • Centre Jean Perrin
      • Colmar, France, 68024
        • Hôpital Louis Pasteur
      • Dijon, France, 21079
        • Centre de Lutte Contre le Cancer Georges-Francois Leclerc
      • Dreux, France, 28100
        • Centre Hospitalier de Dreux
      • Le Chesnay, France, 78157
        • Hôpital André Mignot
      • Le Mans, France, 72037
        • C. H. Du Mans
      • Libourne, France, 33500
        • Hôpital Robert Boulin
      • Lille, France, 59020
        • Centre Oscar Lambret
      • Lyon, France, 69437
        • Hopital Edouard Herriot - Lyon
      • Lyon, France, 69373
        • Centre Leon Berard
      • Marseille, France, 13385
        • CHU de la Timone
      • Marseille, France, 13273
        • Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
      • Mont-de-Marsan, France, 40000
        • Centre Hospitalier General de Mont de Marsan
      • Montpellier, France, 34298
        • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
      • Nantes, France, 44093
        • CHR Hotel Dieu
      • Nantes-Saint Herblain, France, 44805
        • Centre Regional Rene Gauducheau
      • Orleans, France, 45100
        • CHR D'Orleans - Hopital de la Source
      • Paris, France, 75015
        • Hôpital Européen Georges Pompidou
      • Paris, France, 75018
        • Hopital Bichat - Claude Bernard
      • Paris, France, 75674
        • Hopital Cochin
      • Paris, France, 75970
        • Hôpital Tenon
      • Paris, France, 75571
        • Hôpital Saint Antoine
      • Pau, France, 64046
        • Centre Hospitalier - Pau
      • Reims, France, 51092
        • CHU - Robert Debre
      • Rennes, France, 35064
        • Centre Eugène Marquis
      • Rennes, France, 35033
        • Centre Hospitalier Universitaire de Rennes
      • Rouen, France, 76038
        • Centre Henri Becquerel
      • Rouen, France, 76031
        • Hôpital Charles Nicolle
      • Saint Cloud, France, 92210
        • Centre René Huguenin
      • Saint Priest en Jarez, France, 42270
        • Institut de cancérologie de la Loire
      • Strasbourg, France, 67098
        • Hopital Universitaire Hautepierre
      • Strasbourg, France, 67065
        • Centre Paul Strauss
      • Toulouse, France, 31052
        • Institut Claudius Regaud
      • Vandoeuvre-les-Nancy, France, 54511
        • Centre Alexis Vautrin
      • Villejuif, France, F-94805
        • Institut Gustave Roussy
  • Germany
      • Tuebingen, Germany, D-72076
        • Southwest German Cancer Center at Eberhard-Karls-University
  • Spain
      • Leon, Spain, 24008
        • Complejo Hospitalario de León
      • Madrid, Spain, 28700
        • Grupo Espanol de Investigacion del Cancer de Mama
  • United Kingdom
    • England
      • Manchester, England, United Kingdom, M20 4BX
        • Christie Hospital
    • Scotland
      • Glasgow, Scotland, United Kingdom, G12 0YN
        • Gartnavel General Hospital

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 to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed gastrointestinal stromal tumor

    • Localized disease

  • Meets 1 of the following criteria:

    • At high-risk of relapse, defined by 1 of the following criteria:

      • Tumor size > 10 cm
      • Mitotic rate > 10/50 high-power field (HPF)
      • Tumor size > 5 cm AND mitotic rate > 5/50 HPF

    • At intermediate-risk of relapse, defined by 1 of the following criteria:

      • Tumor size < 5 cm AND mitotic rate 6-10/50 HPF
      • Tumor size 5-10 cm AND mitotic rate < 5/50 HPF
  • Tumor must stain positive for Kit (CD117) by polyclonal DAKO antibody staining

  • Must have undergone complete resection of the primary tumor at least 2 weeks, but no more than 3 months, before study entry

    • Meets criteria for 1 of the following resection levels:

      • R0 (clear margins)

      • R1, defined by 1 of the following criteria:

        • Margins of resection are contaminated by tumor, but no macroscopic tumor is left behind
        • Intraoperative tumor rupture
        • Shelling-out procedure
        • Endoscopic maneuver

    • No residual macroscopic disease after surgery

      • Regional positive lymph nodes allowed provided they have been macroscopically excised

  • No distant metastases*, including any of the following:

    • Peritoneal lesion not contiguous to the primary tumor
    • Liver metastases
    • Hemoperitoneal metastases NOTE: *Even if a complete resection (R0) was performed

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • WHO 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL (transfusions allowed)

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST or ALT ≤ 2.5 times ULN
  • No uncontrolled liver disease
  • No chronic viral hepatitis at risk of reactivation

Renal

  • Creatinine < 1.5 times ULN
  • No uncontrolled chronic renal disease

Cardiovascular

  • No New York Heart Association class III-IV cardiac disease
  • No congestive heart failure
  • No myocardial infarction within the past 2 months

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for up to 3 months after study participation
  • No uncontrolled diabetes
  • No uncontrolled active infection
  • No HIV infection
  • No psychological, familial, sociological, or geographical condition that would preclude study compliance or participation
  • No other severe and/or uncontrolled medical disease
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No other prior molecular targeted or biologic therapy
  • No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) to support blood counts
  • No concurrent anticancer biologic agents

Chemotherapy

  • No prior chemotherapy for gastrointestinal stromal tumors
  • No concurrent anticancer chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy
  • No concurrent anticancer radiotherapy

Surgery

  • See Disease Characteristics
  • Prior non-curative surgery allowed (e.g., surgery with main diagnostic intent or emergency surgery with symptomatic intent)

Other

  • No prior imatinib mesylate
  • No prior randomization to this study

  • No concurrent therapeutic anticoagulation with coumarin derivatives

    • Concurrent therapeutic low-molecular weight heparin or mini-dose coumarin derivatives (equivalent to oral warfarin 1 mg/day) allowed for prophylaxis of central venous catheter thrombosis
  • No other concurrent antitumoral therapy
  • No other concurrent anticancer agents
  • No other concurrent investigational drugs

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
Experimental: Imatinib mesylate
400 mg/day for 2 years
Drug: imatinib mesylate
400 mg/day for 2 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall survival

Secondary Outcome Measures

Outcome Measure
Adverse events
Relapse-free survival
Relapse-free interval

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

UNICANCER
Grupo Espanol de Investigacion en Sarcomas
Italian Sarcoma Group

Investigators

  • Study Chair: Axel Le Cesne, MD, Gustave Roussy, Cancer Campus, Grand Paris
  • Study Chair: Paolo G. Casali, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
  • Study Chair: Andres Poveda, MD, Instituto Valenciano de Oncología

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 (Actual)

December 1, 2004

Primary Completion (Actual)

October 1, 2008

Study Completion (Actual)

September 1, 2017

Study Registration Dates

First Submitted

February 7, 2005

First Submitted That Met QC Criteria

February 7, 2005

First Posted (Estimate)

February 8, 2005

Study Record Updates

Last Update Posted (Actual)

July 9, 2018

Last Update Submitted That Met QC Criteria

July 6, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-62024
  • ISG-62024
  • FRE-FNCLCC-EORTC-62024
  • GEIS-EORTC-62024
  • 2004-001810-16 (EudraCT Number)

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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