Ignite Creation Date:
2024-05-06 @ 4:38 PM
Last Modification Date:
2024-10-26 @ 2:13 PM
Study NCT ID:
NCT05044676
Status:
RECRUITING
Last Update Posted:
2023-09-13
First Post:
2021-07-05
Brief Title:
Immune Cells as a New Biomarker of Response in Patients Treated by Immunotherapy for Advanced Hepatocellular Carcinoma
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Assessment of Circulating Immune Cells as a Prognostic Factor in Patients With Advanced Hepatocellular Carcinoma Treated With Immunotherapy
Status:
RECRUITING
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IMMUNOCELL
Brief Summary:
Hepatocellular carcinoma HCC is the third leading cause of cancer death worldwide Treatment options for advanced HCC remain very limited Until recently multikinase inhibitor were the gold standard for advanced hepatocellular carcinoma but associated with poor outcome and important side effects Recently the positive results of the Imbrave 150 study a randomized study comparing Atezolizumab Bevacizumab versus Sorafenib prompted us to redefine our management strategy for advanced hepatocellular carcinoma by proposing the combination of AtezolizumabBevacizumab as treatment first-line in patients with advanced hepatocellular carcinoma However only 13 of the patients will respond to the combination of treatment and identifying predictive factors of response and new immune checkpoint inhibitors in order to target more tumors appear as a major issue In this context recent work has underlined the importance of the activating CD226DNAM-1 receptor as an original immunotherapeutic target in various cancers solid and hematopoietic tumors CD226 is a transmembrane receptor that is part of the immunoglobulin superfamily It is expressed by most T lymphocytes CD8 CD4 by Natural Killer NK cells by promoting their cytotoxicity
The investigators propose to prospectively analyze the frequency and phenotype expression of CD226 of circulating immune cells before the initiation of treatment with AtezolizumabBevacizumab 3 weeks after the first injection and its variation to determine whether this biomarker could predict the response to the treatment
The investigators propose to prospectively analyze the frequency and phenotype expression of CD226 of circulating immune cells before the initiation of treatment with AtezolizumabBevacizumab 3 weeks after the first injection and its variation to determine whether this biomarker could predict the response to the treatment
Detailed Description:
It is now widely accepted that inflammation is an essential element in tumor development Liver tissue is very sensitive to inflammation and harbors immune system effectors capable of preventing the onset of a chronic inflammatory response However in case of chronic liver diseases chronic inflammation will favor fibrosis progression and tumor development Hepatocellular carcinoma HCC is the third leading cause of cancer death worldwide Treatment options for advanced HCC remain very limited Until recently multikinase inhibitor were the gold standard for advanced hepatocellular carcinoma but associated with poor outcome and important side effects Recently immune checkpoint inhibitors have emerged as an innovative anti-tumor strategy to restore an anti-tumor immune response as illustrated by recent positive results of immunotherapy in oncology with prolonged responses in some patients The initial results of immunotherapy in advanced hepatocellular carcinoma as monotherapy have been disappointing However combinations of immunotherapy and anti-VEGF antibodies or between immunotherapy and tyrosine kinase inhibitors are currently being tested in order to potentiate the effect of immunotherapy and to obtain higher rates of anti-tumor response Recently the positive results of the Imbrave 150 study a randomized study comparing Atezolizumab Bevacizumab versus Sorafenib prompted us to redefine our management strategy for advanced hepatocellular carcinoma by proposing the combination of AtezolizumabBevacizumab as treatment first-line in patients with advanced hepatocellular carcinoma However only 13 of the patients will respond to the combination of treatment and identifying predictive factors of response and new immune checkpoint inhibitors in order to target more tumors appear as a major issue In this context recent work has underlined the importance of the activating CD226DNAM-1 receptor as an original immunotherapeutic target in various cancers solid and hematopoietic tumors CD226 is a transmembrane receptor that is part of the immunoglobulin superfamily It is expressed by most T lymphocytes CD8 CD4 by Natural Killer NK cells by promoting their cytotoxicity The ligands for CD226 are the molecules CD112 and CD155 which are overexpressed in many tumors and are associated with a poor prognosis for patients Recent data show that the decrease in CD226 expression on the surface of anti-tumor-containing immune effectors may be associated with resistance to anti-PD1PDL1 immunotherapies To date the involvement of CD226 and its ligands in liver tumorigenesis is completely unknown The use of AtezolizumabBevacizumab in France is a unique opportunity to conduct a pilot study on clinical biological histological molecular and immune prognostic and predictive factors in patients treated with the AtezolizumabBevacizumab combination
The investigators hypothese that a decrease in CD226 expression on the surface of CD8 T lymphocytes CTLs and NK cells before the initiation of treatment with AtezolizumabBevacizumab could be associated with decrease response to the treatment and therefore associated with poor outcome of the patient The investigators propose to prospectively analyze the frequency and phenotype expression of CD226 of circulating immune cells before the initiation of treatment with Atezolizumab Bevacizumab 3 weeks after the first injection day of the second infusion and its variation to determine whether this biomarker could predict the response to the treatment The investigators will also perform an analysis of the histological and pathology characteristics of the tumor and non-tumor liver of the same patient before the initiation of treatment with Atezolizumab Bevacizumab with the ultimate objective of developing a predictive prognostic score for treatment response
The investigators hypothese that a decrease in CD226 expression on the surface of CD8 T lymphocytes CTLs and NK cells before the initiation of treatment with AtezolizumabBevacizumab could be associated with decrease response to the treatment and therefore associated with poor outcome of the patient The investigators propose to prospectively analyze the frequency and phenotype expression of CD226 of circulating immune cells before the initiation of treatment with Atezolizumab Bevacizumab 3 weeks after the first injection day of the second infusion and its variation to determine whether this biomarker could predict the response to the treatment The investigators will also perform an analysis of the histological and pathology characteristics of the tumor and non-tumor liver of the same patient before the initiation of treatment with Atezolizumab Bevacizumab with the ultimate objective of developing a predictive prognostic score for treatment response
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None