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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Italian Sarcoma Group
UNICANCER
Grupo Espanol de Investigacion en Sarcomas
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00103168
First received: February 7, 2005
Last updated: October 28, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Gastrointestinal Stromal Tumor
Drug: imatinib mesylate
Procedure: adjuvant therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Relapse-free survival [ Designated as safety issue: No ]
  • Relapse-free interval [ Designated as safety issue: No ]
  • Adverse events [ Designated as safety issue: Yes ]

Estimated Enrollment: 750
Study Start Date: December 2004
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Compare imatinib monotherapy failure free survival of patients in the two regimens.

Secondary

  • Compare relapse-free survival,relapse-free interval and overall survival in patients treated with these regimens.
  • 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). Patients are randomized to 1 of 2 arms.

  • 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 750 patients will be accrued for this study within 5 years.

  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

    • 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
  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: NCT00103168

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

Additional Information:
No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00103168     History of Changes
Other Study ID Numbers: EORTC-62024, EORTC-62024, ISG-62024, FRE-FNCLCC-EORTC-62024, GEIS-EORTC-62024, 2004-001810-16
Study First Received: February 7, 2005
Last Updated: October 28, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices
Denmark: Danish Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United States: Food and Drug Administration
New Zealand: Medsafe
Australia: Therapeutic Goods Administration
Singapore: Ministry of Health

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