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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00103168




Registration number
NCT00103168
Ethics application status
Date submitted
7/02/2005
Date registered
8/02/2005
Date last updated
9/07/2018

Titles & IDs
Public title
Imatinib Mesylate or Observation Only in Treating Patients Who Have Undergone Surgery for Localized Gastrointestinal Stromal Tumor
Scientific 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
Secondary ID [1] 0 0
EORTC-62024
Secondary ID [2] 0 0
EORTC-62024
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastrointestinal Stromal Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Stomach
Cancer 0 0 0 0
Bowel - Small bowel (duodenum and ileum)
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - imatinib mesylate

Experimental: Imatinib mesylate - 400 mg/day for 2 years

No intervention: Control -


Treatment: Drugs: imatinib mesylate
400 mg/day for 2 years
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
Secondary outcome [1] 0 0
Relapse-free survival
Timepoint [1] 0 0
Secondary outcome [2] 0 0
Relapse-free interval
Timepoint [2] 0 0
Secondary outcome [3] 0 0
Adverse events
Timepoint [3] 0 0

Eligibility
Key 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 age
18 Years
Maximum age
120 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2004
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2017
Sample size
Target
Accrual to date
Final
908
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment outside Australia
Country [1] 0 0
Denmark
State/province [1] 0 0
Herlev
Country [2] 0 0
France
State/province [2] 0 0
Abbeville
Country [3] 0 0
France
State/province [3] 0 0
Angers
Country [4] 0 0
France
State/province [4] 0 0
Besancon
Country [5] 0 0
France
State/province [5] 0 0
Bobigny
Country [6] 0 0
France
State/province [6] 0 0
Bordeaux
Country [7] 0 0
France
State/province [7] 0 0
Boulogne Billancourt
Country [8] 0 0
France
State/province [8] 0 0
Brest
Country [9] 0 0
France
State/province [9] 0 0
Caen
Country [10] 0 0
France
State/province [10] 0 0
Clermont-Ferrand
Country [11] 0 0
France
State/province [11] 0 0
Colmar
Country [12] 0 0
France
State/province [12] 0 0
Dijon
Country [13] 0 0
France
State/province [13] 0 0
Dreux
Country [14] 0 0
France
State/province [14] 0 0
Le Chesnay
Country [15] 0 0
France
State/province [15] 0 0
Le Mans
Country [16] 0 0
France
State/province [16] 0 0
Libourne
Country [17] 0 0
France
State/province [17] 0 0
Lille
Country [18] 0 0
France
State/province [18] 0 0
Lyon
Country [19] 0 0
France
State/province [19] 0 0
Marseille
Country [20] 0 0
France
State/province [20] 0 0
Mont-de-Marsan
Country [21] 0 0
France
State/province [21] 0 0
Montpellier
Country [22] 0 0
France
State/province [22] 0 0
Nantes-Saint Herblain
Country [23] 0 0
France
State/province [23] 0 0
Nantes
Country [24] 0 0
France
State/province [24] 0 0
Orleans
Country [25] 0 0
France
State/province [25] 0 0
Paris
Country [26] 0 0
France
State/province [26] 0 0
Pau
Country [27] 0 0
France
State/province [27] 0 0
Reims
Country [28] 0 0
France
State/province [28] 0 0
Rennes
Country [29] 0 0
France
State/province [29] 0 0
Rouen
Country [30] 0 0
France
State/province [30] 0 0
Saint Cloud
Country [31] 0 0
France
State/province [31] 0 0
Saint Priest en Jarez
Country [32] 0 0
France
State/province [32] 0 0
Strasbourg
Country [33] 0 0
France
State/province [33] 0 0
Toulouse
Country [34] 0 0
France
State/province [34] 0 0
Vandoeuvre-les-Nancy
Country [35] 0 0
France
State/province [35] 0 0
Villejuif
Country [36] 0 0
Germany
State/province [36] 0 0
Tuebingen
Country [37] 0 0
Spain
State/province [37] 0 0
Leon
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid
Country [39] 0 0
United Kingdom
State/province [39] 0 0
England
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Scotland

Funding & Sponsors
Primary sponsor type
Other
Name
European Organisation for Research and Treatment of Cancer - EORTC
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Italian Sarcoma Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
UNICANCER
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Grupo Espanol de Investigacion en Sarcomas
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00103168
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Paolo G. Casali, MD
Address 0 0
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00103168