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Imatinib per os 400 mg daily continuously associated with intravenous administrations of atezolizumab at the fixed dose of 1 200 mg every 3 weeks (up to 12 months)

Imatinib alone, per os 400 mg daily continuously (up to 12 months)

Atezolizumab 1200 mg

Imatinib 400 MG

Julien GAUTIER

Mehdi BRAHMI, MD

Antoine ITALIANO

Loïc LEBELLEC

Florence DUFFAUD, MD

Agnès DUCOULOMBIER

Nicolas ISAMBERT

Olivier BOUCHE, MD

Marc PRACHT

Emmanuelle BOMPAS

Justine GANTZER, MD

Axel LE CESNE, MD

This trial is a prospective, randomized (1:1 ratio), multicenter, comparative and phase II study, conducted in patients with unresectable advanced gastrointestinal stromal tumors (GIST) after failure of imatinib (disease progression),sunitinib and regorafenib (either disease progression or intolerance)

In the first arm, patients will be treated with imatinib + atezolizumab (experimental arm), whereas in the second arm, patients will be treated with imatinib alone (control arm).

The comparison between this two arms will allow to compare whether or not atezolizumab and imatinib is efficient for disease control, in terms of Progression-Free Survival improvement.

This is a prospective, randomized (1:1 ratio), multicenter, comparative and phase II trial.

Patients with unresectable advanced gastrointestinal stromal tumors (GIST) will be accrued after the failure of standard treatments (imatinib, sunitinib and regorafenib) :

* For imatinib, failure is defined as disease progression
* For sunitinib and regorafenib, failure is defined as disease progression and/or intolerance

Randomization (1:1 ratio) will be stratified according to:

* The tumor KIT (exon 11) mutational status: wild type or mutated

STUDY TREATMENTS :

During the treatment period (12 months maximum), all patients will receive either:

* Imatinib per os 400 mg daily continuously associated with intravenous administrations of atezolizumab at the fixed dose of 1200 mg every 3 weeks (experimental arm)
* Or imatinib alone, per os 400 mg daily continuously (control arm)

The comparison between this two arms will allow to compare whether or not atezolizumab and imatinib is efficient for disease control, in terms of Progression-Free Survival improvement.

STATISTICAL ANALYSIS :

A total of 110 patients will be randomized (55 per arm).

It is expected a 6-month PFS rate of 10% in the standard arm (imatinib alone). Thus, a 6-month PFS-rate of 30% is a clinically significant target for patient treated with imatinib associated to immunotherapy.

An interim safety analysis is planned to be conducted after 6-month follow-up of the 12th patient has been randomized (approximately 6 patients by arm).

PFS will be estimated using the Kaplan-Meier method, and will be described in terms of median PFS along with the associated 2-sided 95% CIs for the estimates.

PFS distributions will be compared between the 2 study arms using a stratified Log-Rank test by tumor mutational status of KIT - exon 11 (stratification factors used for the randomisation).

DATA ENTRY, DATA MANAGEMENT AND STUDY MONITORING :

All the data concerning the patients will be recorded in the electronic case report form (eCRF) throughout the study. Serious adverse event (SAE) and Adverse Event of Specific Interest (AESI) reporting will be also paper-based by e-mail and/or Fax.

The sponsor will perform the study monitoring and will help the investigators to conduct the study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local law requirements.

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

Time from the date of randomization to the date of first disease progression, or death from any cause, whichever occurs first

The best response from randomization : Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD)

The proportion of patients with a best overall response of CR or PR during the study

The time from the date of randomization to the date of permanent study treatments discontinuation (any cause, including death, progression, discontinuation of treatment due to progression, toxicity or start of a new anticancer therapy and withdrawal of consent)

The time from the date of randomization to the date of death due to any cause

Assessed using the EORTC QLQ-C30 questionnaire

Described through the incidence and severity of drug-related AEs (AE, SAE, SUSAR, new safety issue) according to the National Cancer Institute Common Terminology Criteria for Adverse Event Version 5 (NCI-CTC AE V5.0)

Centre Leon Berard

Spots Global Cancer Trial Database for atezolizumab 1200 mg