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 (ATEZOGIST)
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ClinicalTrials.gov Identifier: NCT05152472 |
Recruitment Status :
Recruiting
First Posted : December 9, 2021
Last Update Posted : August 1, 2023
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Tracking Information | |||||
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First Submitted Date ICMJE | November 26, 2021 | ||||
First Posted Date ICMJE | December 9, 2021 | ||||
Last Update Posted Date | August 1, 2023 | ||||
Actual Study Start Date ICMJE | January 14, 2022 | ||||
Estimated Primary Completion Date | January 2025 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Progression-Free Survival (PFS) [ Time Frame: 48 months ] Time from the date of randomization to the date of first disease progression, or death from any cause, whichever occurs first
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Original Primary Outcome Measures ICMJE | Same as current | ||||
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Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | 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 | ||||
Official Title ICMJE | 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 | ||||
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. |
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Detailed Description | 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) :
Randomization (1:1 ratio) will be stratified according to:
STUDY TREATMENTS : During the treatment period (12 months maximum), all patients will receive either:
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. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
110 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | June 2026 | ||||
Estimated Primary Completion Date | January 2025 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | INCLUSION CRITERIA : 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); archival tumor sample must be made available for translational research program (in case there is no sufficient archival tumor material available, a biopsy must be performed prior to treatment start); Nota Bene: mutational status and level of expression of PD1/PD-L1 will not be considered as selection criteria but will be studied as endpoints for translational objectives. 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); I11. Patient must be covered by a medical insurance; EXCLUSION CRITERIA : 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; E6. 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); 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:
E8. Patients using or require to use while on the study of any prohibited concomitant and/or concurrent medications (see section "Prohibited concomitant/concurrent treatments) :
E9. Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis (see Appendix 4 for a more comprehensive list of pre-existing autoimmune diseases and immune deficiencies), with the following exceptions:
E10. History of severe allergic / anaphylactic reaction or other hypersensitivity reactions to:
E11. Patients with active infectious disease:
E12. Active or prior history of primary immunodeficiency; E13. Major surgical procedure within 28 days prior to study treatments start, or need for a major surgery during the course of the study; E14. Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within :
E15. Patient that impairs their ability to swallow and retain imatinib or with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of imatinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) E16. Clinically significant unrelated systemic illness (e.g., significant cardiac, pulmonary, hepatic, or other organ dysfunction) that would compromise the patient's ability to tolerate study treatment or would likely interfere with study procedures or results. E17. Patients under tutorship or curatorship. |
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | France | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT05152472 | ||||
Other Study ID Numbers ICMJE | ET19-075- ATEZOGIST | ||||
Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Current Responsible Party | Centre Leon Berard | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | Centre Leon Berard | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | Centre Leon Berard | ||||
Verification Date | July 2023 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |