Study evaluating the interest of imatinib treatment maintenance or interruption after at least 10 years of treatment in patients with locally Advanced or metastatic Gastrointestinal Stromal Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Leon Berard, Centre Leon Berard

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Dec 2021 → ongoing

Decision date (initial)

2024-08-27

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

INCA

External identifiers

EU CT number

2024-512631-77-00

EudraCT number

2021-001430-19

ClinicalTrials.gov

NCT05009927

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To compare the 6-month progression-free rate (PFR-6m) between interruption versus maintenance of imatinib treatment in patients with an advanced/metastatic GIST controlled after 10 years of imatinib
treatment.

Secondary objectives 8

1. To compare between the 2 arms: the progression free survival (PFS);
2. the overall survival (OS);
3. The safety
4. The Quality of Life (QoL).
5. In the interruption arm only: To determine in the subgroup of patients who progressed:the Progression-Free Survival rechallenge (PFS rechallenge);
6. The Objective Response Rate;
7. The duration of response (DOR) after imatinib reintroduction;
8. Translational objectives will be to determine: To identify the genomic (WES) expression profile (RNAseq) and immunologic characteristics of potentially cured patients.

Conditions and MedDRA coding

locally advanced or metastatic Gastrointestinal Stromal Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. I1. Patients ≥ 18 years of age;
2. I2. Histologically documented diagnosis of malignant advanced/metastatic GIST with immunohistochemical documentation of c-kit (CD117) expression either by the primary tumor or metastases;
3. I3. ECOG Performance status (PS) 0, 1, 2;
4. I4. 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;
5. I5. Patient with controlled disease (without any progression under imatinib);
6. I6. Ability to understand and willingness for follow-up visits;
7. I7. Covered by a medical insurance;
8. I8. Signed and dated informed consent document indicating that the patient has been informed of all aspects of the trial prior to enrolment.

Exclusion criteria 10

1. NI1. Patient concurrently using other approved or investigational antineoplastic agents;
2. NI2. Patient with GIST harboring the mutation D842V in PDGFRA ;
3. NI3. 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;
4. NI4. 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) or patient without residual disease for at least 3 years;
5. NI5. Patient receiving concurrent treatment with warfarin (acceptable alternative: low-molecular weight heparin) or any prohibited concomitant and/or concurrent medications;
6. NI6. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection;
7. NI7. Major surgery within 2 weeks prior to study entry;
8. NI8. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study;
9. NI9. Pregnant or breastfeeding women;
10. NI10. Patient requiring tutorship or curatorship or patient deprivied of liberty.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The progression-free rate at 6 months (PFR-6m) expressed in each arm by the rate of patients with a non-progression disease 6 months after randomization.

Secondary endpoints 7

1. PFS will be defined as the 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.
2. OS will be defined as the time from the date of randomization to the date of death due to any cause.
3. The safety will be determined through the incidence of treatment emergent adverse events (TEAE), serious adverse Events (SAE) and death. Tolerance will be assessed using the NCI-CTC AE v5 grading scale.
4. QoL will be assessed using the EORTC QLQ-C30 questionnaire.
5. PFS rechallenge will be defined as 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.
6. ORR after imatinib reintroduction will be defined as the proportion of patients with a best overall response of Partial Response (PR) or Complete Response (CR) after imatinib reintroduction
7. The duration of response to imatinib after reintroduction will be defined as 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Leon Berard

Sponsor organisation

Centre Leon Berard

Address

28 Rue Laennec

City

Lyon

Postcode

69008

Country

France

Scientific contact point

Organisation

Centre Leon Berard

Contact name

BLAY Jean-Yves

Public contact point

Organisation

Centre Leon Berard

Contact name

Clinical Operations Manager

Centre Leon Berard

Sponsor organisation

Centre Leon Berard

Address

28 Rue Laennec

City

Lyon

Postcode

69008

Country

France

Scientific contact point

Organisation

Centre Leon Berard

Contact name

BLAY Jean-Yves

Public contact point

Organisation

Centre Leon Berard

Contact name

Clinical Operations Manager

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications