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

NCT00103168 | Completed Phase 3

• 5 other identifiers: EORTC-62024ISG-62024FRE-FNCLCC-EORTC-62024GEIS-EORTC-620242004-001810-16
• Study Type: interventional
• Target: 908
• Locations: 6 countries
• Sites: 50

Brief Summary

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.

Conditions

Gastrointestinal Stromal Tumor

Keywords

gastrointestinal stromal tumor

Outcome Measures

Primary Outcomes (1)

• Overall survival

Secondary Outcomes (3)

• Relapse-free survival

• Relapse-free interval

• Adverse events

Study Arms (2)

Imatinib mesylate

EXPERIMENTAL

400 mg/day for 2 years

Drug: imatinib mesylate

Control

NO INTERVENTION

Interventions

imatinib mesylate DRUG

400 mg/day for 2 years

Imatinib mesylate

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Italian Sarcoma Group: collaborator
• UNICANCER: collaborator
• Grupo Espanol de Investigacion en Sarcomas: collaborator

Study Sites (50)

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Herlev University Hospital

Herlev, DK-2730, Denmark

Location

Centre Hospitalier d'Abbeville

Abbeville, 80101, France

Location

Centre Paul Papin

Angers, 49036, France

Location

Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz

Besançon, 25030, France

Location

Hopital Avicenne

Bobigny, 93009, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Hopital Ambroise Pare

Boulogne-Billancourt, 92100, France

Location

C.H.U. de Brest

Brest, 29200, France

Location

Centre Regional Francois Baclesse

Caen, 14076, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Hopital Louis Pasteur

Colmar, 68024, France

Location

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, 21079, France

Location

Centre Hospitalier de Dreux

Dreux, 28100, France

Location

Hopital Andre Mignot

Le Chesnay, 78157, France

Location

C. H. Du Mans

Le Mans, 72037, France

Location

Hopital Robert Boulin

Libourne, 33500, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Hopital Edouard Herriot - Lyon

Lyon, 69437, France

Location

Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

Marseille, 13273, France

Location

CHU de la Timone

Marseille, 13385, France

Location

Centre Hospitalier General de Mont de Marsan

Mont-de-Marsan, 40000, France

Location

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, 34298, France

Location

CHR Hotel Dieu

Nantes, 44093, France

Location

Centre Regional Rene Gauducheau

Nantes-Saint Herblain, 44805, France

Location

CHR D'Orleans - Hopital de la Source

Orléans, 45100, France

Location

Hopital Europeen Georges Pompidou

Paris, 75015, France

Location

Hopital Bichat - Claude Bernard

Paris, 75018, France

Location

Hopital Saint Antoine

Paris, 75571, France

Location

Hopital Cochin

Paris, 75674, France

Location

Hopital Tenon

Paris, 75970, France

Location

Centre Hospitalier - Pau

Pau, 64046, France

Location

CHU - Robert Debre

Reims, 51092, France

Location

Centre Hospitalier Universitaire de Rennes

Rennes, 35033, France

Location

Centre Eugene Marquis

Rennes, 35064, France

Location

Hopital Charles Nicolle

Rouen, 76031, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Centre Rene Huguenin

Saint-Cloud, 92210, France

Location

Institut de Cancerologie de la Loire

Saint-Priest-en-Jarez, 42270, France

Location

Centre Paul Strauss

Strasbourg, 67065, France

Location

Hopital Universitaire Hautepierre

Strasbourg, 67098, France

Location

Institut Claudius Regaud

Toulouse, 31052, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy

Villejuif, F-94805, France

Location

Southwest German Cancer Center at Eberhard-Karls-University

Tübingen, D-72076, Germany

Location

Complejo Hospitalario de Leon

León, 24008, Spain

Location

Grupo Espanol de Investigacion del Cancer de Mama

Madrid, 28700, Spain

Location

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

Location

Gartnavel General Hospital

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Related Publications (2)

• Gronchi A, Bonvalot S, Poveda Velasco A, Kotasek D, Rutkowski P, Hohenberger P, Fumagalli E, Judson IR, Italiano A, Gelderblom HJ, van Coevorden F, Penel N, Kopp HG, Duffaud F, Goldstein D, Broto JM, Wardelmann E, Marreaud S, Smithers M, Le Cesne A, Zaffaroni F, Litiere S, Blay JY, Casali PG. Quality of Surgery and Outcome in Localized Gastrointestinal Stromal Tumors Treated Within an International Intergroup Randomized Clinical Trial of Adjuvant Imatinib. JAMA Surg. 2020 Jun 1;155(6):e200397. doi: 10.1001/jamasurg.2020.0397. Epub 2020 Jun 17.

  PMID: 32236507 DERIVED

• Casali PG, Le Cesne A, Poveda Velasco A, Kotasek D, Rutkowski P, Hohenberger P, Fumagalli E, Judson IR, Italiano A, Gelderblom H, Adenis A, Hartmann JT, Duffaud F, Goldstein D, Broto JM, Gronchi A, Dei Tos AP, Marreaud S, van der Graaf WT, Zalcberg JR, Litiere S, Blay JY. Time to Definitive Failure to the First Tyrosine Kinase Inhibitor in Localized GI Stromal Tumors Treated With Imatinib As an Adjuvant: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Intergroup Randomized Trial in Collaboration With the Australasian Gastro-Intestinal Trials Group, UNICANCER, French Sarcoma Group, Italian Sarcoma Group, and Spanish Group for Research on Sarcomas. J Clin Oncol. 2015 Dec 20;33(36):4276-83. doi: 10.1200/JCO.2015.62.4304. Epub 2015 Nov 16.

  PMID: 26573069 DERIVED

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2005
• First Posted: February 8, 2005
• Study Start: December 1, 2004
• Primary Completion: October 1, 2008
• Study Completion: September 1, 2017
• Last Updated: July 9, 2018

Record last verified: 2018-07

Locations

GB (2); AU (1); FR (43); DE (1); ES (2); DK (1)