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

Gastrointestinal Stromal Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00103168
• Other study ID #: EORTC-62024
• Secondary ID: EORTC-62024ISG-6
• Status: Completed
• Phase: Phase 3
• Start date: December 2004
• Est. completion date: September 2017

Study information

• Verified date: July 2018
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 908
• Est. completion date: September 2017
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumor
• Gastrointestinal Stromal Tumors

Intervention

Drug:
• imatinib mesylate
400 mg/day for 2 years

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Denmark	Herlev University Hospital	Herlev
France	Centre Hospitalier d'Abbeville	Abbeville
France	Centre Paul Papin	Angers
France	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz	Besancon
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	CHU de la Timone	Marseille
France	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes	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	Orleans
France	Hopital Bichat - Claude Bernard	Paris
France	Hopital Cochin	Paris
France	Hopital Europeen Georges Pompidou	Paris
France	Hopital Saint Antoine	Paris
France	Hopital Tenon	Paris
France	Centre Hospitalier - Pau	Pau
France	CHU - Robert Debre	Reims
France	Centre Eugene Marquis	Rennes
France	Centre Hospitalier Universitaire de Rennes	Rennes
France	Centre Henri Becquerel	Rouen
France	Hopital Charles Nicolle	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	Vandoeuvre-les-Nancy
France	Institut Gustave Roussy	Villejuif
Germany	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen
Spain	Complejo Hospitalario de Leon	Leon
Spain	Grupo Espanol de Investigacion del Cancer de Mama	Madrid
United Kingdom	Gartnavel General Hospital	Glasgow	Scotland
United Kingdom	Christie Hospital	Manchester	England

Sponsors (4)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Grupo Espanol de Investigacion en Sarcomas, Italian Sarcoma Group, UNICANCER

Countries where clinical trial is conducted

Australia,  Denmark,  France,  Germany,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival
Secondary	Relapse-free survival
Secondary	Relapse-free interval
Secondary	Adverse events