Detail Article

Informations générales (source: ClinicalTrials.gov)

Numéro NCT

NCT05009927 En recrutement IDF

Titre

Randomized, Multicentre, Phase II Study Evaluating the Interest of Imatinib Treatment Maintenance or Interruption After at Least 10 Years of Treatment in Patients With Locally Advanced/Metastatic Gastrointestinal Stromal Tumors (GISTs)

Type

Interventional

Pathologie

Tumeurs
Tumeurs stromales gastro-intestinales

Phase

Phase 2

Promoteur

Centre Leon Berard (Voir sur ClinicalTrials)

Date de début

janvier 2022

Date de fin

janvier 2027

Dernière mise à jour

29 juin 2024

Résumé

This is a 2 arms study concerning patients under imatinib treatment for at least 10 years of treatment with locally advanced/metastatic GIST. In the first arm, patients will discontinue Imatinib treatment. This arm will allow to determine if the re-introduction of Imatinib at relapse is still an efficient treatment for the control of disease. In the second arm, patients will continue Imatinib treatment, allowing to determine if the continuation of this treatment is efficient for disease control, by the rate of non-progression disease.

Détail

Voir le détail Gastrointestinal stromal tumors (GISTs) arise from mesenchymal stem cells which also give rise to the interstitial cells of Cajal within the GI tract. A large majority of GIST tumors harbour activating mutations in the proto-oncogenes KIT and/or PDGFRA, both coding cell-surface cytokine receptors with tyrosine-protein kinase activity. Imatinib mesilate (Glivec®, Novartis Pharma SAS) is a selective tyrosine kinase inhibitor, leading to inhibition of KIT and PDGFRA signalling pathways. The introduction of imatinib has revolutionised the therapeutic management of GIST patients and has provided an unprecedented demonstration of the clinical benefit of a targeted therapy for patients with advanced/metastatic solid tumors. Several studies have investigated the optimal duration of imatinib treatment in the advanced phase. The BFR14 trial demonstrated that 31% of advanced GIST patients treated with continuous imatinib beyond 1 year had documented disease progression compared to 81% in the interrupted imatinib group (p<0.0001). The authors concluded that treatment interruption resulted in rapid progression in most patients with advanced GIST and therefore should not be recommended in standard practice unless the patient experienced significant toxicity or disease progression. An update of the BFR14 trial at a median follow-up of 37 months showed that 91% of patients in the interrupted arm versus 62% in the continuous arm experienced progressive disease (p<0.0001). Majority (92%) of patients in the interrupted arm achieved tumor control once they recommenced imatinib after first progression. Ray-Coquard et al. reported that stopping imatinib after 5 years resulted in a higher rate of disease progression than imatinib maintenance in patients with advanced GIST responding to or stabilised by imatinib. However, whether lifelong imatinib treatment duration is mandatory in metastatic GIST patients remains unclear. It is not known whether a cytostatic treatment of 10 years or longer is sufficient to inhibit definitively GIST cancer cells proliferation even after the interruption of the kinase inhibitor. This question has broad implications for all targeted therapies. The aim of the present study is to address this question rigorously in a randomized setting. The investigators therefore want to determine whether prolonged use of imatinib beyond 10 years is needed to reduce the risk of GIST recurrence and to improve overall survival. For patients with imatinib interruption after at least 10 years of treatment, the investigators want to determine if imatinib rechallenge is efficient for treating recurrence. Therefore, the investigators design an open-label, randomized, multicenter phase II study to determine the clinical impact of maintaining imatinib treatment beyond 10 years in patients with locally advanced/metastatic GIST. Fermer le détail

Etablissements

Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données
CLCC INSTITUT GUSTAVE ROUSSY	Axel LE CESNE	En recrutement IDF	18/02/2024 15:59:10	Contacter
Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
CLCC INSTITUT CURIE	Sophie PIPERNO NEUMANN	Recrutement non commencé		Contact (sur clinicalTrials)
Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
Centre Eugène Marquis - 35042 - Rennes - France		Recrutement non commencé		Contact (sur clinicalTrials)
Centre Léon Bérard - 69373 - Lyon - France	Jean-Yves BLAY, PhD	En recrutement		Contact (sur clinicalTrials)
CHU Besançon - 25000 - Besançon - France	Elsa KALBACHER, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Reims - 51100 - Reims - France	Olivier BOUCHE, PhD	En recrutement		Contact (sur clinicalTrials)
CHU Dupuytren - 87042 - Limoges - France	Valérie LE BRUN LY, MD	En recrutement		Contact (sur clinicalTrials)
Institut Bergonié - 33076 - Bordeaux - France	Antoine ITALIANO	En recrutement		Contact (sur clinicalTrials)
Institut Claudius Regaud - 31059 - Toulouse - France	Valentin THIBAUD	Recrutement non commencé		Contact (sur clinicalTrials)
Institut de Cancérologie de Lorraine - 54519 - Vandœuvre-lès-Nancy - France	Maria RIOS, MD	Recrutement non commencé		Contact (sur clinicalTrials)
Institut de Cancérologie de l'Ouest - Site Réné Gauducheau - 44805 - Saint-Herblain - France	Emanuelle BOMPAS	Recrutement non commencé		Contact (sur clinicalTrials)
Institut de Cancérologie Lucien NEUWIRTH - 42270 - Saint-Paul-en-Jarez - France	Olivier COLLARD, MD	Recrutement non commencé		Contact (sur clinicalTrials)
Institut Paoli Calmettes - 13273 - Marseille - France	François BERTUCCI, PhD	Recrutement non commencé		Contact (sur clinicalTrials)

Critères

Genre

Tous

Nombre d'inclusion

Critère d'inclusion

Inclusion Criteria:

- Patients ≥18 years of age;

- Histologically documented diagnosis of malignant advanced/metastatic GIST with
immunohistochemical documentation of c-kit (CD117) expression either by the primary
tumor or metastases;

- Eastern Cooperative Oncology Group (ECOG) - Performance status (PS) 0 to 2 evaluated
within 7 days prior to the date of inclusion.

- Patient must be under imatinib treatment (at 300 or 400mg/day) maintained for 10
years or over with no more than 12 months in total or 3 consecutive months of
interruption during the treatment period;

- Patient with controlled disease (without any progression under imatinib);

- Willingness and ability to comply with scheduled visits, treatment plans ,
laboratory tests, and other study procedures;

- Covered by a medical/health insurance;

- Signed and dated informed consent document indicating that the patient has been
informed of all aspects of the trial prior to enrolment.

Critère de non inclusion

- Patient concurrently using other approved or investigational antineoplastic agents;

- Patient with GIST harboring the mutation D842V in PDGFRA;

- Major concurrent disease affecting cardiovascular system, liver, kidneys,
haematopoietic system or else considered as clinically important by the investigator
and that could be incompatible with patient's participation in this trial or would
likely interfere with study procedures or results;

- Prior history of other malignancies other than study disease (except for basal cell
or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless
the patient has been free of the disease for at least 3 years;

- Patient receiving concurrent treatment with warfarin (acceptable alternative:
low-molecular weight heparin) or any prohibited concomitant and/or concurrent
medications

- Patient has a known diagnosis of human immunodeficiency virus (HIV) infection;

- Major surgery within 2 weeks prior to study entry.

- Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the study.

- Pregnant or breastfeeding woman

- Patient requiring tutorship or curatorship or patient deprivied of liberty.

NCT05009927 - Randomized, Multicentre, Phase II Study Evaluating the Interest of Imatinib Treatment Maintenance or Interruption After at Least 10 Years of Treatment in Patients With Locally Advanced/Metastatic Gastrointestinal Stromal Tumors (GISTs)

Informations générales
Etablissements
Critères
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