Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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.

Further Study Information

OBJECTIVES:

Primary

• Compare the effect of adjuvant imatinib mesylate vs observation only on the prognosis of patients with completely resected localized gastrointestinal stromal tumors at intermediate- or high-risk of relapse.

• Compare overall survival of patients treated with these regimens.

Secondary

• Compare relapse-free survival and relapse-free interval 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 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

Trial Contact Information

Trial Lead Organizations/Sponsors

European Organization for Research and Treatment of Cancer

Paolo G. Casali

Axel Le Cesne

Andres Poveda

Australia
South Australia
	Bedford Park
	Flinders Medical Centre
		Contact Person	Ph: 61-8-204-5267
Denmark
	Herlev
	Copenhagen County Herlev University Hospital
		Contact Person	Ph: 45-44-88-44-88
France
	Abbeville
	Centre Hospitalier d'Abbeville
		Mathieu Pauwels	Ph: 33-03-2225-5200
	Angers
	Centre Paul Papin
		Veronique Guerin-Meyer, MD	Ph: 33-2-4135-2700
	Besancon
	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
		Loic Chaigneau	Ph: 33-03-8166-8724
	Bobigny
	Hopital Avicenne
		Gaetan Des Guetz, MD	Ph: 33-1-4895-5033
	Bordeaux
	Institut Bergonie
		Nguyen Binh Bui, MD	Ph: 33-556-333-333
	Boulogne Billancourt
	Hopital Ambroise Pare
		Philippe Rougier, MD	Ph: 33-1-49-095-325
			Email: philippe.rougier@apr.aphp.fr
	Brest
	C.H.U. de Brest
		Jean-Philippe Metges, MD	Ph: 33-2-9822-3333
	Caen
	Centre Regional Francois Baclesse
		Corinne Delcambre	Ph: 33-2-3145-5012
	Clermont-Ferrand
	Centre Jean Perrin
		Jacques-Olivier Bay, MD, PhD	Ph: 33-04-7327-8131
	Colmar
	Hopital Louis Pasteur
		Faress Husseini, MD	Ph: 33-3-8912-4489
			Email: fares.husseini@ch-colmar.rss.fr
	Dijon
	Centre de Lutte Contre le Cancer Georges-Francois Leclerc
		Pierre Fargeot, MD	Ph: 33-38-073-7506
			Email: pfargeot@dijon.frclcc.fr
	Dreux
	Centre Hospitalier de Dreux
		Alain Landau, MD	Ph: 33-2-3751-5300
			Email: alandau@ch-dreux.fr
	Le Chesnay
	Hopital Andre Mignot
		Didier Mayeur, MD	Ph: 33-1-3963-8909
			Email: dmayeur@ch-versailles.fr
	Le Mans
	C. H. Du Mans
		Marie-Aude Coulon	Ph: 33-2-4343-4364
	Libourne
	Hopital Robert Boulin
		Dominique Auby	Ph: 33-5-5755-3555
			Email: dominique.auby@cheibourne.aquisante.fr
	Lille
	Centre Oscar Lambret
		Antoine Adenis, MD, PhD	Ph: 33-320-29-59-42
			Email: a-adenis@o-lambret.fr
	Lyon
	Centre Leon Berard
		Isabelle Ray-Coquard, MD	Ph: 33-04-7878-2644
	Hopital Edouard Herriot - Lyon
		Jean-Yves Blay, MD, PhD	Ph: 33-47-211-7398
			Email: jy.blay@chu-lyon.fr
	Marseille
	CHU de la Timone
		Florence Duffaud, MD	Ph: 33-4-9138-5708
			Email: fduffaud@mail.ap-hm.fr
	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
		Francois Bertucci, MD	Ph: 33-4-9122-3537
	Mont-de-Marsan
	Centre Hospitalier General de Mont de Marsan
		Patrick Texereau, MD	Ph: 33-5-5805-1164
	Montpellier
	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
		Didier Cupissol, MD, PhD	Ph: 33-04-67-613-183
			Email: dcupissol@valdorel.fnclcc.fr
	Nantes
	CHR Hotel Dieu
		Bruno Buecher	Ph: 33-2-4080-3151
	Nantes-Saint Herblain
	Centre Regional Rene Gauducheau
		Emmanuelle Bompas	Ph: 33-2-40-479-959
	Orleans
	CHR D'Orleans - Hopital de la Source
		Jean-Paul Lagasse	Ph: 33-02-3851-4704
	Paris
	Hopital Bichat - Claude Bernard
		Thomas Aparicio	Ph: 33-1-4025-7200
			Email: thomas.aparicio@bch.ap-hop-paris.fr
	Hopital Cochin
		Francois Goldwasser, MD, PhD	Ph: 33-158-411-746
			Email: francois.goldwasser@cch.aphp.fr
	Hopital Europeen Georges Pompidou
		Bruno Landi, MD	Ph: 33-1-5609-3555
			Email: bruno.landi@egp.aphp.fr
	Hopital Saint Antoine
		Christophe Louvet, MD, PhD	Ph: 33-1-4928-2345
			Email: christophe.louvet@sat.aphp.fr
	Hopital Tenon
		Thierry Andre, MD	Ph: 33-1-6177-0708
			Email: thierry.andre@tnn.ap-hop-paris.fr
	Pau
	Centre Hospitalier - Pau
		Alexandre Pariente	Ph: 33-05-5992-4983
			Email: alexandre.pariente@ch-pau.fr
	Reims
	CHU - Robert Debre
		Olivier Bouche, MD, PhD	Ph: 33-3-2678-7169
			Email: obouche@chu-reims.fr
	Rennes
	Centre Eugene Marquis
		J.L. Raoul, MD, PhD	Ph: 33-2-9925-3172
			Email: raoul@rennes.fnlcc.fr
	Centre Hospitalier Universitaire de Rennes
		Sylvain Manfredi, MD	Ph: 33-2-9928-4317
			Email: sylvain.manfredi@chu-rennes.fr
	Rouen
	Centre Henri Becquerel
		Cecile Guillemet, MD	Ph: 33-02-32-02-2237
			Email: cecile.guillemet@rouen.fnclcc.fr
	Hopital Charles Nicolle
		Pierre Michel	Ph: 33-02-3288-6456
	Saint Cloud
	Centre Rene Huguenin
		Frederique B. Cvitkovic, MD	Ph: 33-1-4711-1824
			Email: f.cvitkovic@stcloud-huguenin.org
	Saint Priest En Jarez
	Institut de Cancerologie de la Loire
		Olivier Collard, MD	Ph: 33-477-91-7036
	Strasbourg
	Centre Paul Strauss
		Patrick R. Dufour, MD	Ph: 33-388-252-401
			Email: pdufour@strasbourg.fnclcc.fr
	Hopital Universitaire Hautepierre
		Jean-Emmanuel Kurtz, MD	Ph: 33-3-88-12-8314
	Toulouse
	Institut Claudius Regaud
		Christine Chevreau-Dalbianco, MD	Ph: 33-5-6142-4119
			Email: chevreau.christine@claudiusregaud.fr
	Vandoeuvre-les-Nancy
	Centre Alexis Vautrin
		Maria Rios, MD	Ph: 33-3-8359-8331
			Email: m.rios@nancy.fnclcc.fr
	Villejuif
	Institut Gustave Roussy
		Axel Le Cesne, MD	Ph: 33-1-4211-4211
			Email: lecesne@igr.fr
Germany
	Tuebingen
	Southwest German Cancer Center at Eberhard-Karls-University
		Contact Person	Ph: 49-7071-292-711
Spain
	Leon
	Complejo Hospitalario de Leon
		Contact Person	Ph: 34-987-237-400
	Madrid
	Grupo Espanol de Investigacion del Cancer de Mama
		Contact Person	Ph: 34-91-425-0620
United Kingdom
England
	Manchester
	Christie Hospital
		Contact Person	Ph: 44-845-226-3000
Scotland
	Glasgow
	Gartnavel General Hospital
		Contact Person	Ph: 44-141-211-3242

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00103168
Information obtained from ClinicalTrials.gov on November 20, 2012

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