Metastatic Gastrointestinal Stromal Tumor (GIST)Phase 2NCT05009927
Efficiency of Imatinib Treatment After 10 Years of Treatment in Patients With Gastrointestinal Stromal Tumours (GIST) (Gist-Ten)
A Phase 2 study testing Imatinib tablets in people with Metastatic Gastrointestinal Stromal Tumor (GIST) and C-KIT Mutation, run by Centre Leon Berard at 13 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Gastrointestinal Stromal Tumor (GIST), C-KIT Mutation, Advanced Gastrointestinal Stromal Tumor (GIST)
- What is being tested?
- Imatinib tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 13 sitesFrance
- Study dates
- 3 Jan 2022to Jan 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 10Show fewer
- 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.
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
France13 sites, 13 recruiting
- Recruiting
CHU Besançon
Besançon, 25000
Elsa KALBACHER, MD, 03.70.63.24.03, ekalbacher@chu-besancon.fr
Elsa KALBACHER, MD
- Recruiting
Institut Bergonié
Bordeaux, 33076
Antoine ITALIANO, A.Italiano@bordeaux.unicancer.fr
Antoine ITALIANO
- Recruiting
CHU Dupuytren
Limoges, 87042
Valérie LE BRUN LY, MD, valerie.lebrunly@chu-limoges.fr
- Recruiting
Centre Léon Bérard
Lyon, 69373
Jean-Yves BLAY, PhD
04 78 78 27 57, jean-yves.blay@lyon.unicancer.fr
- Not yet recruiting
Institut Paoli Calmettes
Marseille, 13273
François BERTUCCI, PhD, bertuccif@ipc.unicancer.fr
François BERTUCCI, PhD
- Not yet recruiting
Institut Curie
Paris, 75005
Sophie PIPERNO NEUMANN, sophie.piperno-neumann@curie.fr
Sophie PIPERNO NEUMANN
- Recruiting
CHU de Reims
Reims, 51100
Olivier BOUCHE, PhD
Olivier BOUCHE, PhD
- Not yet recruiting
Centre Eugène Marquis
Rennes, 35042
Christophe PERRIN, MD
Marc PRACHT, MD
- Not yet recruiting
Institut de Cancérologie de l'Ouest - Site Réné Gauducheau
Saint-Herblain, 44805
Emanuelle BOMPAS
Emanuelle BOMPAS
- Not yet recruiting
Institut de Cancérologie Lucien NEUWIRTH
Saint-Paul-en-Jarez, 42270
Olivier COLLARD, MD, Olivier.COLLARD@icloire.fr
Olivier COLLARD, MD
- Not yet recruiting
Institut Claudius Regaud
Toulouse, 31059
Valentin THIBAUD, valentin.Thibaud@iuct-oncopole.fr
Valentin THIBAUD
- Not yet recruiting
Institut de Cancérologie de Lorraine
Vandœuvre-lès-Nancy, 54519
Maria RIOS, MD
Maria RIOS, MD
- Recruiting
Institut Goustave Roussy
Villejuif, 94805
Axel LE CESNE, PhD, 01 42 11 43 16, axel.lecesne@gustaveroussy.fr
Axel LE CESNE, PhD
About this study
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)
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.
Read the 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.
- Conditions
- Metastatic Gastrointestinal Stromal Tumor (GIST), C-KIT Mutation, Advanced Gastrointestinal Stromal Tumor (GIST)
- Being tested
- Imatinib tablets
- Keywords
- Gastrointestinal Stromal Tumors (GIST), Tyrosine kinase inhibitor, Maintenance therapy, Bayesian design, KIT +, Imatinib, Randomisation study
- Medical subject headings
- Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib tabletsDrug
Also called Glivec
Imatinib interruption
| Study group | Role | What they receive |
|---|---|---|
| Imatinib interruption | Experimental | 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. Receives: Drug: Imatinib tablets |
| Imatinib maintenancce | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free-rate at 6 months (PFR 6m)
Defined as the rate of patients with a non-progressive disease 6 months after randomization
Measured: 6 months after randomization
Secondary outcomes (7)
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
Measured: 5 years (i.e. at the the time of last patient last visit)
Overall Survival (OS)
the time from the date of randomization to the date of death due to any cause.
Measured: 5 years (i.e. at the the time of last patient last visit)
Safety profile
The assessment of safety will be based mainly on the frequency of AE based on the Common Toxicity Criteria version 5
Measured: 5 years (i.e. at the the time of last patient last visit)
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).
Measured: 5 years (i.e. at the the time of last patient last visit)
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.
Measured: 5 years (i.e. at the the time of last patient last visit)
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
Measured: 5 years (i.e. at the the time of last patient last visit)
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.
Measured: 5 years (i.e. at the the time of last patient last visit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2021
- Study start3 Jan 2022
- Primary completionJan 2025 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Gastrointestinal Stromal Tumor (GIST)Studies of the same condition, open and under way.
- More trials run by Centre Leon BerardThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Leon Berard
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Yves BLAY, Pr, Principal investigator, Centre Léon Bérard, Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05009927
- Sponsor's protocol ID
- GIST-TEN
- Status last verified
- Aug 2023
- First submitted
- 2 Aug 2021
- Last updated
- 1 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05009927
- Acronym / sponsor ID
- GIST-TEN
- Conditions
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Centre Leon BerardUniversity, hospital or other
- Study start
- 3 Jan 2022 (actual)
- Primary completion
- Jan 2025 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 18 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Imatinib interruption | Experimental | Drug: Imatinib tabletsImmediate 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. |
| Imatinib maintenancce | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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);
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imatinib tabletsAlso: GlivecImatinib interruption | Drug | Imatinib interruption |
Primary outcome
Progression-free-rate at 6 months (PFR 6m)
Time frame: 6 months after randomization
Defined as the rate of patients with a non-progressive disease 6 months after randomization
7 secondary outcomes
Progression-free-survival (PFS)
Time frame: 5 years (i.e. at the the time of last patient last visit)
Overall Survival (OS)
Time frame: 5 years (i.e. at the the time of last patient last visit)
Safety profile
Time frame: 5 years (i.e. at the the time of last patient last visit)
Quality of Life (QoL)
Time frame: 5 years (i.e. at the the time of last patient last visit)
Progression-free survival rechallenge
Time frame: 5 years (i.e. at the the time of last patient last visit)
Objective Response Rate (ORR) after imatinib reintroduction
Time frame: 5 years (i.e. at the the time of last patient last visit)
Duration of response (DOR)
Time frame: 5 years (i.e. at the the time of last patient last visit)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2023.
Related trials for Metastatic Gastrointestinal Stromal Tumor (GIST)
RecruitingPhase 2
A Study to Learn More About How Well Treatment With Sevabertinib (BAY 2927088) Tablets Works and How Safe it is in Participants Who Have a Solid Tumor With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)
Advanced Solid Tumors, HER2 Mutation
RecruitingPhase 3
A Study to Investigate Velzatinib Compared With Imatinib in Adult Participants With Previously Untreated Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (StrateGIST Frontline)
Gastrointestinal Stromal Neoplasms
Active, not recruitingPhase 2
A Prospective, Randomized, Multicenter, Comparative Study of the Efficacy of Imatinib Resumption Combined With Atezolizumab Versus Imatinib Resumption Alone in Patients With Unresectable Advanced Gastrointestinal Stromal Tumors (GIST) After Failure of Standard Treatments
Unresectable Gastrointestinal Stromal Tumor (GIST), Locally Advanced Gastrointestinal Stromal Tumor (GIST)
Not yet recruitingPhase 2
Autologous Tumor Infiltrating Lymphocytes With Interleukin-2 for the Treatment of Locally Advanced, Recurrent or Metastatic Gastrointestinal Stromal Tumors
Locally Advanced Gastrointestinal Stromal Tumor, Metastatic Gastrointestinal Stromal Tumor
Active, not recruitingPhase 1
First-in-human Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors
Gastrointestinal Neoplasms, Gastrointestinal Stromal Tumor (GIST)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jean-Yves BLAY, Pr principal investigator
Centre Léon Bérard, Lyon
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imatinib tablets in people with Metastatic Gastrointestinal Stromal Tumor (GIST) and C-KIT Mutation, run by Centre Leon Berard at 13 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jean-Yves BLAY, Pr (+33 4 78 78 27 57, jean-yves.blay@lyon.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free-rate at 6 months (PFR 6m) (time frame: 6 months after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2023.