Efficiency of Imatinib Treatment After 10 Years of Treatment in Patients With Gastrointestinal Stromal Tumours (GIST) (Gist-Ten)

NCT ID: NCT05009927

Last Updated: 2023-09-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-01-03

Study Completion Date

2027-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Metastatic Gastrointestinal Stromal Tumor (GIST) C-KIT Mutation Advanced Gastrointestinal Stromal Tumor (GIST)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Imatinib interruption

Immediate interruption of imatinib until progressive disease. In case of 1st relapse, imatinib will be reintroduced at 400mg/d and further increased at 800mg/d in case of 2nd relapse after re-introduction.

Group Type EXPERIMENTAL

Imatinib tablets

Intervention Type DRUG

Imatinib interruption

Imatinib maintenancce

Maintenance of imatinib at the last dose routinely taken by the patient in the 10-year period prior to randomization (either 300 or 400 mg once daily). In case of progressive disease imatinib will be increased up to 800mg/day.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Imatinib tablets

Imatinib interruption

Intervention Type DRUG

Other Intervention Names

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Glivec

Eligibility Criteria

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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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centre Leon Berard

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Yves BLAY, Pr

Role: PRINCIPAL_INVESTIGATOR

Centre Léon Bérard, Lyon

Locations

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CHU Besançon

Besançon, , France

Site Status RECRUITING

Institut Bergonié

Bordeaux, , France

Site Status RECRUITING

CHU Dupuytren

Limoges, , France

Site Status RECRUITING

Centre Léon Bérard

Lyon, , France

Site Status RECRUITING

Institut Paoli Calmettes

Marseille, , France

Site Status NOT_YET_RECRUITING

Institut Curie

Paris, , France

Site Status NOT_YET_RECRUITING

CHU de Reims

Reims, , France

Site Status RECRUITING

Centre Eugène Marquis

Rennes, , France

Site Status NOT_YET_RECRUITING

Institut de Cancérologie de l'Ouest - Site Réné Gauducheau

Saint-Herblain, , France

Site Status NOT_YET_RECRUITING

Institut de Cancérologie Lucien NEUWIRTH

Saint-Paul-en-Jarez, , France

Site Status NOT_YET_RECRUITING

Institut Claudius Regaud

Toulouse, , France

Site Status NOT_YET_RECRUITING

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, , France

Site Status NOT_YET_RECRUITING

Institut Goustave Roussy

Villejuif, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Jean-Yves BLAY, Pr

Role: CONTACT

+33 4 78 78 27 57

Facility Contacts

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Elsa KALBACHER, MD

Role: primary

03.70.63.24.03

Antoine ITALIANO

Role: primary

Valérie LE BRUN LY, MD

Role: primary

Jean-Yves BLAY, PhD

Role: primary

Role: backup

04 78 78 27 57

François BERTUCCI, PhD

Role: primary

Sophie PIPERNO NEUMANN

Role: primary

Olivier BOUCHE, PhD

Role: primary

Emanuelle BOMPAS

Role: primary

Olivier COLLARD, MD

Role: primary

Valentin THIBAUD

Role: primary

Maria RIOS, MD

Role: primary

Axel LE CESNE, PhD

Role: primary

01 42 11 43 16

Other Identifiers

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GIST-TEN

Identifier Type: -

Identifier Source: org_study_id

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