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

NCT ID: NCT00103168

Last Updated: 2018-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 908 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-31
• Study Completion Date: 2017-09-30

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.

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.

Conditions

Gastrointestinal Stromal Tumor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Imatinib mesylate

400 mg/day for 2 years

Group Type: EXPERIMENTAL

imatinib mesylate

Intervention Type: DRUG

400 mg/day for 2 years

Control

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

imatinib mesylate

400 mg/day for 2 years

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Italian Sarcoma Group

NETWORK

Sponsor Role: collaborator

UNICANCER

OTHER

Sponsor Role: collaborator

Grupo Espanol de Investigacion en Sarcomas

OTHER

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paolo G. Casali, MD

Role: STUDY_CHAIR

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Axel Le Cesne, MD

Role: STUDY_CHAIR

Gustave Roussy, Cancer Campus, Grand Paris

Andres Poveda, MD

Role: STUDY_CHAIR

Instituto Valenciano De Oncologia

Locations

Flinders Medical Centre

Bedford Park, South Australia, Australia

Herlev University Hospital

Herlev, , Denmark

Centre Hospitalier d'Abbeville

Abbeville, , France

Centre Paul Papin

Angers, , France

Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz

Besançon, , France

Hopital Avicenne

Bobigny, , France

Institut Bergonie

Bordeaux, , France

Hopital Ambroise Pare

Boulogne-Billancourt, , France

C.H.U. de Brest

Brest, , France

Centre Regional Francois Baclesse

Caen, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Hopital Louis Pasteur

Colmar, , France

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, , France

Centre Hospitalier de Dreux

Dreux, , France

Hopital Andre Mignot

Le Chesnay, , France

C. H. Du Mans

Le Mans, , France

Hopital Robert Boulin

Libourne, , France

Centre Oscar Lambret

Lille, , France

Centre Leon Berard

Lyon, , France

Hopital Edouard Herriot - Lyon

Lyon, , France

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

Marseille, , France

CHU de la Timone

Marseille, , France

Centre Hospitalier General de Mont de Marsan

Mont-de-Marsan, , France

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

Montpellier, , France

CHR Hotel Dieu

Nantes, , France

Centre Regional Rene Gauducheau

Nantes-Saint Herblain, , France

CHR D'Orleans - Hopital de la Source

Orléans, , France

Hopital Europeen Georges Pompidou

Paris, , France

Hopital Bichat - Claude Bernard

Paris, , France

Hopital Saint Antoine

Paris, , France

Hopital Cochin

Paris, , France

Hopital Tenon

Paris, , France

Centre Hospitalier - Pau

Pau, , France

CHU - Robert Debre

Reims, , France

Centre Hospitalier Universitaire de Rennes

Rennes, , France

Centre Eugene Marquis

Rennes, , France

Hopital Charles Nicolle

Rouen, , France

Centre Henri Becquerel

Rouen, , France

Centre Rene Huguenin

Saint-Cloud, , France

Institut de Cancerologie de la Loire

Saint-Priest-en-Jarez, , France

Centre Paul Strauss

Strasbourg, , France

Hopital Universitaire Hautepierre

Strasbourg, , France

Institut Claudius Regaud

Toulouse, , France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Institut Gustave Roussy

Villejuif, , France

Southwest German Cancer Center at Eberhard-Karls-University

Tübingen, , Germany

Complejo Hospitalario de Leon

León, , Spain

Grupo Espanol de Investigacion del Cancer de Mama

Madrid, , Spain

Christie Hospital

Manchester, England, United Kingdom

Gartnavel General Hospital

Glasgow, Scotland, United Kingdom

Countries

Australia; Denmark; France; Germany; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 32236507 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26573069 (View on PubMed)

Other Identifiers

EORTC-62024

Identifier Type: -

Identifier Source: secondary_id

ISG-62024

Identifier Type: -

Identifier Source: secondary_id

FRE-FNCLCC-EORTC-62024

Identifier Type: -

Identifier Source: secondary_id

GEIS-EORTC-62024

Identifier Type: -

Identifier Source: secondary_id

2004-001810-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EORTC-62024

Identifier Type: -

Identifier Source: org_study_id