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

Primary Purpose

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

Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Imatinib tablets
Sponsored by
Centre Leon Berard
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Gastrointestinal Stromal Tumor (GIST) focused on measuring Gastrointestinal Stromal Tumors (GIST), Tyrosine kinase inhibitor, Maintenance therapy, Bayesian design, KIT +, Imatinib, Randomisation study

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • CHU BesançonRecruiting
  • Institut BergoniéRecruiting
  • CHU DupuytrenRecruiting
  • Centre Léon BérardRecruiting
  • Institut Paoli Calmettes
  • Institut Curie
  • CHU de ReimsRecruiting
  • Centre Eugène Marquis
  • Institut de Cancérologie de l'Ouest - Site Réné Gauducheau
  • Institut de Cancérologie Lucien NEUWIRTH
  • Institut Claudius Regaud
  • Institut de Cancérologie de Lorraine
  • Institut Goustave RoussyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Imatinib interruption

Imatinib maintenancce

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Progression-free-rate at 6 months (PFR 6m)
Defined as the rate of patients with a non-progressive disease 6 months after randomization

Secondary Outcome Measures

Progression-free-survival (PFS)
Time from the date of randomization to the date of the first documented progression, or date of death due to any cause. Patients with no event at the time of the analysis will be censored at the date of last available tumor assessment
Overall Survival (OS)
the time from the date of randomization to the date of death due to any cause.
Safety profile
The assessment of safety will be based mainly on the frequency of AE based on the Common Toxicity Criteria version 5
Quality of Life (QoL)
QoL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire (QLQ-C30).
Progression-free survival rechallenge
the time from the date of imatinib reintroduction in the experimental arm to the date of subsequent progression, or date of death due to any cause. Patients with no event at the time of the analysis will be censored at the the date of last available tumor assessment.
Objective Response Rate (ORR) after imatinib reintroduction
Defined as the proportion of patients with a best overall response of Partial Response (PR) or Complete Response (CR) after imatinib reintroduction
Duration of response (DOR)
the time from the date of first objective response following the reintroduction of imatinib to the date of the first subsequent documented radiological progression or death and censored at the date of last available tumor assessment.

Full Information

First Posted
August 2, 2021
Last Updated
August 31, 2023
Sponsor
Centre Leon Berard
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1. Study Identification

Unique Protocol Identification Number
NCT05009927
Brief Title
Efficiency of Imatinib Treatment After 10 Years of Treatment in Patients With Gastrointestinal Stromal Tumours (GIST) (Gist-Ten)
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 3, 2022 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Leon Berard

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Gastrointestinal Stromal Tumor (GIST), C-KIT Mutation, Advanced Gastrointestinal Stromal Tumor (GIST)
Keywords
Gastrointestinal Stromal Tumors (GIST), Tyrosine kinase inhibitor, Maintenance therapy, Bayesian design, KIT +, Imatinib, Randomisation study

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Imatinib interruption
Arm Type
Experimental
Arm Description
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.
Arm Title
Imatinib maintenancce
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Imatinib tablets
Other Intervention Name(s)
Glivec
Intervention Description
Imatinib interruption
Primary Outcome Measure Information:
Title
Progression-free-rate at 6 months (PFR 6m)
Description
Defined as the rate of patients with a non-progressive disease 6 months after randomization
Time Frame
6 months after randomization
Secondary Outcome Measure Information:
Title
Progression-free-survival (PFS)
Description
Time from the date of randomization to the date of the first documented progression, or date of death due to any cause. Patients with no event at the time of the analysis will be censored at the date of last available tumor assessment
Time Frame
5 years (i.e. at the the time of last patient last visit)
Title
Overall Survival (OS)
Description
the time from the date of randomization to the date of death due to any cause.
Time Frame
5 years (i.e. at the the time of last patient last visit)
Title
Safety profile
Description
The assessment of safety will be based mainly on the frequency of AE based on the Common Toxicity Criteria version 5
Time Frame
5 years (i.e. at the the time of last patient last visit)
Title
Quality of Life (QoL)
Description
QoL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire (QLQ-C30).
Time Frame
5 years (i.e. at the the time of last patient last visit)
Title
Progression-free survival rechallenge
Description
the time from the date of imatinib reintroduction in the experimental arm to the date of subsequent progression, or date of death due to any cause. Patients with no event at the time of the analysis will be censored at the the date of last available tumor assessment.
Time Frame
5 years (i.e. at the the time of last patient last visit)
Title
Objective Response Rate (ORR) after imatinib reintroduction
Description
Defined as the proportion of patients with a best overall response of Partial Response (PR) or Complete Response (CR) after imatinib reintroduction
Time Frame
5 years (i.e. at the the time of last patient last visit)
Title
Duration of response (DOR)
Description
the time from the date of first objective response following the reintroduction of imatinib to the date of the first subsequent documented radiological progression or death and censored at the date of last available tumor assessment.
Time Frame
5 years (i.e. at the the time of last patient last visit)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jean-Yves BLAY, Pr
Phone
+33 4 78 78 27 57
Email
jean-yves.blay@lyon.unicancer.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Yves BLAY, Pr
Organizational Affiliation
Centre Léon Bérard, Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Besançon
City
Besançon
ZIP/Postal Code
25000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elsa KALBACHER, MD
Phone
03.70.63.24.03
Email
ekalbacher@chu-besancon.fr
First Name & Middle Initial & Last Name & Degree
Elsa KALBACHER, MD
First Name & Middle Initial & Last Name & Degree
Loïc CHAIGNEAU, MD
First Name & Middle Initial & Last Name & Degree
Guillaume MEYNARD, MD
Facility Name
Institut Bergonié
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antoine ITALIANO
Email
A.Italiano@bordeaux.unicancer.fr
First Name & Middle Initial & Last Name & Degree
Antoine ITALIANO
First Name & Middle Initial & Last Name & Degree
Maud TOULMONDE
First Name & Middle Initial & Last Name & Degree
Kevin BOURCIER
First Name & Middle Initial & Last Name & Degree
Sophie COUSIN
Facility Name
CHU Dupuytren
City
Limoges
ZIP/Postal Code
87042
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valérie LE BRUN LY, MD
Email
valerie.lebrunly@chu-limoges.fr
Facility Name
Centre Léon Bérard
City
Lyon
ZIP/Postal Code
69373
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Yves BLAY, PhD
Phone
04 78 78 27 57
Email
jean-yves.blay@lyon.unicancer.fr
First Name & Middle Initial & Last Name & Degree
Jean-Yves BLAY, PhD
First Name & Middle Initial & Last Name & Degree
Mehdi BRAHMI
First Name & Middle Initial & Last Name & Degree
Armelle DUFRESNE
First Name & Middle Initial & Last Name & Degree
Isabelle RAY-COQUARD
Facility Name
Institut Paoli Calmettes
City
Marseille
ZIP/Postal Code
13273
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
François BERTUCCI, PhD
Email
bertuccif@ipc.unicancer.fr
First Name & Middle Initial & Last Name & Degree
François BERTUCCI, PhD
First Name & Middle Initial & Last Name & Degree
Audrey MONNEUR
First Name & Middle Initial & Last Name & Degree
Elika LOIR
First Name & Middle Initial & Last Name & Degree
Simon LAUNAY
First Name & Middle Initial & Last Name & Degree
Frédéric VIRET
First Name & Middle Initial & Last Name & Degree
Brice CHANEZ
First Name & Middle Initial & Last Name & Degree
Delphine LOUVEL PERROT
Facility Name
Institut Curie
City
Paris
ZIP/Postal Code
75005
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sophie PIPERNO NEUMANN
Email
sophie.piperno-neumann@curie.fr
First Name & Middle Initial & Last Name & Degree
Sophie PIPERNO NEUMANN
Facility Name
CHU de Reims
City
Reims
ZIP/Postal Code
51100
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivier BOUCHE, PhD
First Name & Middle Initial & Last Name & Degree
Olivier BOUCHE, PhD
First Name & Middle Initial & Last Name & Degree
Mathilde BRASSEUR, MD
First Name & Middle Initial & Last Name & Degree
Damien BOTSEN, MD
Facility Name
Centre Eugène Marquis
City
Rennes
ZIP/Postal Code
35042
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christophe PERRIN, MD
First Name & Middle Initial & Last Name & Degree
Marc PRACHT, MD
First Name & Middle Initial & Last Name & Degree
Angélique BRUNOT, MD
First Name & Middle Initial & Last Name & Degree
Astrid LIEVRE, PhD
First Name & Middle Initial & Last Name & Degree
Eugénie RIGAULT, MD
First Name & Middle Initial & Last Name & Degree
Thomas GRAINVILLE, MD
First Name & Middle Initial & Last Name & Degree
Anne-Sophie MOUSSADDAQ, MD
Facility Name
Institut de Cancérologie de l'Ouest - Site Réné Gauducheau
City
Saint-Herblain
ZIP/Postal Code
44805
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emanuelle BOMPAS
First Name & Middle Initial & Last Name & Degree
Emanuelle BOMPAS
First Name & Middle Initial & Last Name & Degree
Fréderic ROLLAND
First Name & Middle Initial & Last Name & Degree
Damien VANSTEENE
Facility Name
Institut de Cancérologie Lucien NEUWIRTH
City
Saint-Paul-en-Jarez
ZIP/Postal Code
42270
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivier COLLARD, MD
Email
Olivier.COLLARD@icloire.fr
First Name & Middle Initial & Last Name & Degree
Olivier COLLARD, MD
First Name & Middle Initial & Last Name & Degree
Cécile VASSAL, MD
Facility Name
Institut Claudius Regaud
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valentin THIBAUD
Email
valentin.Thibaud@iuct-oncopole.fr
First Name & Middle Initial & Last Name & Degree
Valentin THIBAUD
First Name & Middle Initial & Last Name & Degree
Iphigénie KORAKIS
First Name & Middle Initial & Last Name & Degree
Christine CHEVREAU
Facility Name
Institut de Cancérologie de Lorraine
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54519
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria RIOS, MD
First Name & Middle Initial & Last Name & Degree
Maria RIOS, MD
Facility Name
Institut Goustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Axel LE CESNE, PhD
Phone
01 42 11 43 16
Email
axel.lecesne@gustaveroussy.fr
First Name & Middle Initial & Last Name & Degree
Axel LE CESNE, PhD
First Name & Middle Initial & Last Name & Degree
Rastislav BAHLEDA, MD
First Name & Middle Initial & Last Name & Degree
Olivier MIR, MD
First Name & Middle Initial & Last Name & Degree
Benjamin VERRET, MD

12. IPD Sharing Statement

Learn more about this trial

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

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