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

NCT05152472 | Recruiting Phase 2 DMC

• 1 other identifier: ET19-075- ATEZOGIST
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Unresectable Gastrointestinal Stromal Tumor (GIST); Locally Advanced Gastrointestinal Stromal Tumor (GIST); Metastatic Gastrointestinal Stromal Tumor

Keywords

Oncology; Imatinib; Atezolizumab; Immunotherapy; Phase II; Unresectable Gastrointestinal Stromal Tumor; Locally Advanced Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Stromal Tumor; GIST; Tyrosine kinase inhibitor; Progression-Free Survival; Best Response Rate; Objective Response Rate; Time to Treatment Failure; Overall Survival; Quality of Life; Tolerability; Randomization

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

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

  48 months

Secondary Outcomes (6)

• Best Response Rate (BRR)

  48 months

• Objective Response Rate (ORR)

  48 months

• Time to Treatment Failure (TTF)

  48 months

• Overall Survival (OS)

  48 months

• Quality of Life (QoL)

  Up to 12 months

Study Arms (2)

Imatinib + Atezolizumab

EXPERIMENTAL

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)

Drug: Atezolizumab 1200 mg; Drug: Imatinib 400 MG

Imatinib alone

ACTIVE COMPARATOR

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

Drug: Imatinib 400 MG

Interventions

Atezolizumab 1200 mg DRUG

(Intravenous administration)

Also known as: Tecentriq®

Imatinib + Atezolizumab

Imatinib 400 MG DRUG

(Per os)

Also known as: Glivec®

Imatinib + Atezolizumab; Imatinib alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• I1. Male or female ≥ 18 years at the day of consenting to the study;
• I2. Patients must have histologically confirmed diagnosis of GIST (within the French Reference Network in Pathology of Sarcomas - RRePS network);
• I3. Locally advanced or metastatic disease confirmed as measurable according to the RECIST V1.1 (Appendix 1);
• I4. Patients who previously failed to at least imatinib, sunitinib and then regorafenib. Failure is defined for Imatinib as progressive disease, and for sunitinib and regorafenib as progressive disease and/or intolerance;
• I5. Performance Status of the ECOG of 0 or 1;
• I6. Adequate bone marrow and organ function defined by the following laboratory results:
• a. Bone marrow: i. Hemoglobin ≥ 9.0 g/dl, ii. Absolute Neutrophils Count (ANC) ≥ 1.5 G/l, iii. Lymphocytes count ≥ 0.5 G/l, iv. Platelets ≥ 100 G/l;
• b. Coagulation: i. Prothrombin time ≤ 1.5 x Upper Limit of the Normal (ULN) for patients without therapeutic anticoagulation.
• Patients with therapeutic anticoagulation must have stable dose of treatment.
• c. Hepatic function: i. Total serum bilirubin ≤ 1.5 x ULN (except patients with Gilbert's syndrome who must have total serum bilirubin ≤ 3.0 x ULN), ii. Transaminases (ASAT/ALAT) ≤ 2.5 x ULN (or ≤ 5.0 x ULN in case of documented liver metastases) iii. Alkaline Phosphatases ≤ 2.5 x ULN (or ≤ 5.0 x ULN in case of documented bone metastases),
• d. Renal function: i. Serum creatinine ≤ 1.5 x ULN or Cr. Cl. ≥ 40ml/min/1.73m² (MDRD or CKD-EPI formula);
• I7. Willingness and ability to comply with the study requirements;
• I8. Signed and dated informed consent indicating that the patient has been informed of all the aspects of the trial prior to enrolment;
• I9. Women of childbearing potential are required to have a negative serum pregnancy test within 72 hours prior to study treatment start. A positive urine test must be confirmed by a serum pregnancy test;
• I10. Women of childbearing potential and male patients must agree to use adequate highly effective contraception for the duration of study participation (Appendix 3);

You may not qualify if:

• E1. Prior malignancy within the last 3 years except for locally curable disease with no sign of relapse;
• E2. Patients in whom imatinib had been already reintroduced after sunitinib as second line;
• E3. Known D842V mutation in Exon 18 of PDGFRA;
• E4. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4 , anti-TIGIT, anti PD-1,and anti PD-L1 therapeutic antibodies;
• E5. Any approved anticancer therapy (chemotherapy, hormonal therapy or radiotherapy) or treatment with any investigational product within 2 weeks or within 5 elimination half-lives (whichever is longer) prior to study treatments start;
• E7. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
• Asymptomatic patients with treated CNS lesions are eligible, provided that all of the following criteria are met:
• Measurable disease, per RECIST v1.1, must be present outside the CNS.
• The patient has no history of intracranial hemorrhage or spinal cord hemorrhage.
• The patient has not undergone stereotactic radiotherapy within 7 days prior to randomization, whole-brain radiotherapy within 14 days prior to randomization, or neurosurgical resection within 28 days prior to randomization.
• The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted.
• Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord).
• There is no evidence of interim progression between completion of CNS-directed therapy and randomization.
• Spinal cord compression not definitively treated with surgery and/or radiation, and/or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for 2 weeks prior to screening.
• History of leptomeningeal disease.

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (13)

Centre Léon Bérard

Lyon, Rhône, 69373, France

RECRUITING

Institut Bergonié

Bordeaux, 33076, France

RECRUITING

Centre Oscar Lambret

Lille, 59020, France

RECRUITING

Hôpital de La Timone

Marseille, 13385, France

RECRUITING

Centre Antoine Lacassagne

Nice, 06189, France

RECRUITING

CHU Poitiers

Poitiers, 86000, France

RECRUITING

Hôpital Robert Debré

Reims, 51090, France

RECRUITING

Centre Eugène Marquis

Rennes, 35042, France

RECRUITING

Institut de cancérologie de l'Ouest

Saint-Herblain, 44805, France

RECRUITING

Centre Paul Strauss

Strasbourg, 67033, France

NOT YET RECRUITING

ICANS CHRU de Strasbourg

Strasbourg, 67200, France

TERMINATED

Chru Tours

Tours, 37044, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94805, France

RECRUITING

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Neoplasms

Interventions

atezolizumab; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Mehdi BRAHMI, MD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julien GAUTIER

CONTACT

+33 4 26 55 68 29; julien.gautier@lyon.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2021
• First Posted: December 9, 2021
• Study Start: January 14, 2022
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

FR (13)