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

Centre Leon Berard24 个研究点分布在 1 个国家目标入组 110 人2022年1月14日

适应症Unresectable Gastrointestinal Stromal Tumor (GIST)Locally Advanced Gastrointestinal Stromal Tumor (GIST)Metastatic Gastrointestinal Stromal Tumor

干预措施Atezolizumab 1200 mg Imatinib 400 MG

概览

阶段: 2 期
干预措施: Atezolizumab 1200 mg
疾病 / 适应症: Unresectable Gastrointestinal Stromal Tumor (GIST)
发起方: Centre Leon Berard
入组人数: 110
试验地点: 24
主要终点: Progression-Free Survival (PFS)
状态: 招募中
最后更新: 8天前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

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.

详细描述

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). A statistical interim analysis will be conducted after 50 events (PFS). Predefined stopping rules for futility will be applied to state on the continuation of the trial. 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.

注册库

clinicaltrials.gov

开始日期

2022年1月14日

结束日期

2027年10月1日

最后更新

8天前

研究类型

Interventional

研究设计

Parallel

性别

All

研究者

发起方

Centre Leon Berard

责任方

Sponsor

入排标准

入选标准

•Male or female ≥ 18 years at the day of consenting to the study;
•Patients must have histologically confirmed diagnosis of GIST (within the French Reference Network in Pathology of Sarcomas - RRePS network);
•Locally advanced or metastatic disease confirmed as measurable according to the RECIST V1.1 (Appendix 1);
•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;
•Performance Status of the ECOG of 0 or 1;
•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),

排除标准

•Prior malignancy within the last 3 years except for locally curable disease with no sign of relapse;
•Patients in whom imatinib had been already reintroduced after sunitinib as second line;
•Known D842V mutation in Exon 18 of PDGFRA;
•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;
•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;
•Residual adverse events from prior anticancer therapy that has not resolved to grade ≤1, except for alopecia and lab values (provided that inclusion criteria described in section 6.1 are met);
•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.

研究组 & 干预措施

Imatinib + Atezolizumab

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)

干预措施: Atezolizumab 1200 mg

Imatinib + Atezolizumab

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)

干预措施: Imatinib 400 MG