Clinical Trial Results:
A randomized, multicentre, phase III trial evaluating the interest of imatinib treatment maintenance or interruption after 3 years of adjuvant treatment in patients with Gastrointestinal Stromal Tumours (GIST)
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Summary
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EudraCT number |
2013-001372-37 |
Trial protocol |
FR |
Global end of trial date |
07 Dec 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Nov 2025
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First version publication date |
15 Nov 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ET13-024
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Centre Léon Bérard
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Sponsor organisation address |
28 Rue Laënnec, Lyon, France,
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Public contact |
SEVERINE METZGER, CENTRE LEON BERARD, +33 0478782786 , severine.metzger@lyon.unicancer.fr
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Scientific contact |
SEVERINE METZGER, CENTRE LEON BERARD, +33 0478782786 , severine.metzger@lyon.unicancer.fr
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Sep 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Dec 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Dec 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the clinical impact, in terms of Disease-Free Survival (DFS), of interruption versus maintenance of imatinib adjuvant treatment beyond 3 years, in patients with resected primary GIST at high risk of recurrence
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Protection of trial subjects |
Information of patient and informed consent signature will be performed prior to any study-specific procedure. The patient will be orally provided by the investigator with the appropriate information; in
addition, he will be given written information and an informed consent form. After a sufficient time to think, the patient will give his written consent, by dating and signing the inform consent form. This form will also be signed and dated by the investigator, preferentially on the same day, and a copy will be given to the patient (the original form will be archived in the patient medical file).
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
22 Dec 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 136
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Worldwide total number of subjects |
136
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EEA total number of subjects |
136
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
136
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||
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Pre-assignment
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Screening details |
A screening visit should take place within 4 weeks (i.e. 28 days) prior to the programmed date of randomization, knowing that randomization (M0 visit) must be 36 months (± 3 months) after the start date of imatinib adjuvant treatment. | |||||||||
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Period 1
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Period 1 title |
Overall study period (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Arm 1 | |||||||||
Arm description |
Maintenance of imatinib at the last dose routinely taken by the patient in the 3-year period prior to randomization (either 300 or 400 mg/d) | |||||||||
Arm type |
Standard treatment | |||||||||
Investigational medicinal product name |
Glivec®
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Investigational medicinal product code |
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Other name |
Imatinib mesilate
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Imatinib mesilate (Glivec®, Novartis) is a selective inhibitor of KIT, PDGFRA and BCR-ABL protein tyrosine kinase activity and is commercialized by Novartis Pharma SAS. Imatinib (300, 400 or 800mg/d) must be taken orally with a meal and a large glass of water until PD or unacceptable toxicity as per Glivec SPC.
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Arm title
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Arm 2 | |||||||||
Arm description |
Interruption of imatinib treatment from the day of randomization. | |||||||||
Arm type |
Interruption | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Arm 1
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Reporting group description |
Maintenance of imatinib at the last dose routinely taken by the patient in the 3-year period prior to randomization (either 300 or 400 mg/d) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm 2
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Reporting group description |
Interruption of imatinib treatment from the day of randomization. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Arm 1
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Reporting group description |
Maintenance of imatinib at the last dose routinely taken by the patient in the 3-year period prior to randomization (either 300 or 400 mg/d) | ||
Reporting group title |
Arm 2
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Reporting group description |
Interruption of imatinib treatment from the day of randomization. | ||
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End point title |
Disease Free survival [1] | |||||||||||||||
End point description |
Disease-Free Survival (DFS), will be analysed based on the data from the ITT population, according to the study arm and randomization strata to which patients were assigned. It will be measured from the date of randomization to the date of event defined as the first documented relapse or death due to any cause. Patients with no event at the time of the analysis will be censored at the date of the last adequate tumour assessment. The distribution of DFS will be estimated using the Kaplan-Meier method. The median DFS along with 95% CI will be presented by study arm. The primary efficacy analysis will be the comparison of the distribution of DFS between the two arms using a log-rank test stratified by randomization stratification factors at two-sided 5% level of significance. A Cox regression model stratified by randomization stratification factors will be used to estimate the hazard ratio (HR) of DFS, along with 95% CI
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End point type |
Primary
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End point timeframe |
Disease-free survival was defined as the time from randomization to the first date of relapse or death from any cause. Patients without relapse were censored at the date of the last available tumor assessment. DFS after 3y of adjuvant imatinib treatment.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Time to imatinib resistance was calculated as the time from randomization to first progression on imatinib or death. Seven patients in the maintenance arm relapsed while on treatment. In the interruption arm, five patients progressed after restarting treatment and three died without restarting treatment. The 3-year disease-free survival rates on imatinib were 93% and 96% in the maintenance and interruption arms, respectively. |
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| No statistical analyses for this end point | ||||||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
All period
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Adverse event reporting additional description |
Adverse event (AE): any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product, and which does not necessarily have a causal relationship with this treatment. All AEs will be reported in the CRF.
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
27.1
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| Frequency threshold for reporting non-serious adverse events: 5% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Regarding safety, 123 (90.4%) patients experienced at least one AE, 56 (86.2%) and 67 (94.4%) in the discontinuation and maintenance groups, respectively. The incidence of grade 3 or higher adverse events (AEs) was not significantly different between discontinuation and maintenance (n=19, [29.2%] vs. 13 [18.3%], p>0.05), with a similar number of serious AEs in both arms (13 [20.0%] vs. 13 [18.3%]). Myalgia was the only side effect significantly different between the two arms. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 Oct 2014 |
• Modification des impératifs concernant la méthode de contraception à utiliser dans le cadre de l’étude (une méthode contraceptive au lieu de deux) et modification du critère d’inclusion I9 en conséquence
• Signaler le changement de la personne de contact auprès du promoteur
• Mise à jour de la liste des investigateurs :
- Déclarer 3 nouveaux investigateurs :
- Signaler le changement d’adresse d'un Centre
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13 Jan 2015 |
• Déclarer un nouveau lieu de recherche
• Mettre à jour la liste des investigateurs :
- Déclarer un investigateur
- Supprimer 3 investigateurs
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28 Apr 2015 |
• Déclarer un nouveau lieu de recherche :
• Mettre à jour la liste des investigateurs :
Déclarer 6 investigateurs
Supprimer un investigateur
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08 Mar 2016 |
* Mise à jour de la liste des investigateurs :
Déclarer un nouveau lieu de recherche
Déclarer le changement d’investigateur principal
Supprimer un lieu de recherche
Déclarer 8 nouveaux investigateurs dans des lieux de recherche déjà déclarés
Supprimer un investigateur
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07 Jun 2016 |
* Mise à jour de la liste des investigateurs
Déclarer un nouveau lieu de recherche
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20 Sep 2016 |
Déclarer un nouveau lieu de recherche |
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13 Jun 2017 |
* Mise à jour de la liste des investigateurs :
Déclarer un nouveau lieu de recherche
Déclarer le changement d’investigateur principal
Déclarer 3 nouveaux investigateurs
Supprimer un investigateur
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13 Feb 2018 |
• Prolongation de 2 ans de la durée des inclusions
• Mise à jour de la liste des investigateurs :
Déclarer un nouveau lieu de recherche :
Déclarer de nouveaux investigateurs dans des lieux de recherche déjà déclarés
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18 Dec 2018 |
• Réévaluation du nombre de patients à inclure : 134 patients au lieu des 256 initialement planifiés ;
• Mise à jour de la section vigilance ;
• Mise en conformité des documents de l’étude suite à la législation européenne (Règlement Général sur la Protection des Données « RGPD ») ;
• Actualisation du paragraphe « Sponsor Responsibilities » selon les procédures du promoteur ;
• Modification de certains termes suite à la loi Jardé ;
• Actualisation de la liste des abréviations ;
• Mise à jour de la liste des investigateurs : déclaration de 2 nouveaux investigateurs dans des lieux déjà déclarés et retrait d’un investigateur
Déclaration nouveaux investigateurs :
Retrait d’un investigateur :
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15 Oct 2019 |
• Prolongation de 2 ans de la durée des inclusions initialement prévue (7 ans au lieu de 5 ans) et en conséquence de la durée totale de l’étude ainsi que la dernière visite du dernier patient (sans modification de la durée de traitement ni de suivi) ;
• Actualisation des données du RGPD (durée archivage maximale).
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14 Jan 2020 |
• Mise à jour de la liste des investigateurs (changement d'investigateur principal (IP) et déclaration d’un nouvel investigateur dans un lieu de recherche déjà déclaré) :
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23 Mar 2021 |
• Mise à jour de la liste des investigateurs (changement d'investigateur principal (IP) et déclaration d’un nouvel investigateur dans un lieu de recherche déjà déclaré) |
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18 Jan 2022 |
• Prolongation de la durée d’inclusions ;
• Mise à jour des documents de l’étude suite à la publication du Règlement Général sur la Protection des Données (RGPD) ;
• Mise à jour de la liste des investigateurs.
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21 Jun 2022 |
• Mise à jour de la liste des investigateurs :
Changement du nom d'un centre
Ajout d’un lieu de recherche
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11 May 2023 |
• Mise à jour de la liste des investigateurs (changement d’investigateur principal « IP » dans un lieu de recherche déjà déclaré) |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
