LILIPSY: Liver Cancer and Immunotherapy in the Liquid Biopsy Era

Sponsor

University Hospital, Montpellier (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05810402

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The goal of this prospective clinical trial is to identify a predictive biomarker in patients with advanced HCC (stage B and C) using a combinatorial approach of the liquid biopsy.

The main questions it aims to answer are:

Is multi-omic liquid biopsy approach able to identify a strong predictive biomarker of immunotherapy efficiency?
Is there a correlation between tissue biopsy (PD-L1 tissue level of expression) and liquid biopsy (detection of CTC expressing PD-L1) in HCC patients?

Participants blood will be collected at several time points.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma BCLC Stage B Hepatocellular Carcinoma BCLC Stage C Hepatocellular Carcinoma Immune Checkpoint Inhibitor Liquid Biopsy	Biological: Liquid Biopsy	N/A

Detailed Description

In solid cancers, some more aggressive tumor cells actively detach from the primary lesion and then travel through the circulating compartment to reach distant organs and form micro-metastases. Detecting CTCs in the blood is also relevant for assessing tumor progression, prognosis and therapeutic follow-up. The non-invasive, highly sensitive for CTCs analysis is called "liquid biopsy". Over the past few years, a multi-analyses approach (CTCs, circulating tumor DNA, extracellular vesicles, miRNA...) of liquid biopsy has been developed.

Hepatocellular carcinoma (HCC) is the predominant pathological type of primary liver cancer. It represents the sixth most common incidence worldwide and the third most common cause of cancer mortality.

Since 2021, the gold standard treatment for patients with advanced and/or unresectable HCC is the combination of atezolizumab (anti-PD-L1) and bevacizumab (VEGF inhibitor) in cases where chemoembolization is not indicated (patients with lymph node invasion and/or distant lesions or patients with portal flow abnormality). Indeed, this therapy offers a significant benefit in overall survival (19.2 vs 13.4 months, HR 0.66, p<0.0009) as well as in progression-free survival (6.9 vs 4.3 months, HR 0.65, p=0.0001). However, to date, there is no predictive biomarker for the efficacy of immune checkpoint inhibitors (ICI)

The purpose of this research project is to identify a predictive biomarker in patients with advanced HCC (stage B and C) using a combinatorial approach of the liquid biopsy (CTC, CTC expressing PD-L1, immune cell profiling).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Homogenous cohort of BCLC Stage B and C hepatocellular carcinoma patients that will undergo immunotherapy +/- anti-angiogenic agent (bevacizumab)Homogenous cohort of BCLC Stage B and C hepatocellular carcinoma patients that will undergo immunotherapy +/- anti-angiogenic agent (bevacizumab)

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Liver Cancer and Immunotherapy : Clinical Relevance of LIquid BioPSY

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

May 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BCLC B and C HCC patients For each participant, 30mL of blood will be collected at inclusion/before treatment initiation (baseline) and during standard of care follow-up. The blood sample will be taken, in consultation or in outpatient clinic during a blood test for health purposes.	Biological: Liquid Biopsy 30mL blood sample: 1 x 10mL CellSave tube specifically designed for the collection and preservation of CTCs for CellSearch® analysis 1 EDTA tube for PBMCs isolation and circulating immune cells study (5mL), 2 EDTA tubes and 1 dry tube (15mL) for the preparation of the biobank (serum, plasma and cell). Other Names: Blood sample

Arm

Intervention/Treatment

Experimental: BCLC B and C HCC patients

For each participant, 30mL of blood will be collected at inclusion/before treatment initiation (baseline) and during standard of care follow-up. The blood sample will be taken, in consultation or in outpatient clinic during a blood test for health purposes.

Biological: Liquid Biopsy

30mL blood sample: 1 x 10mL CellSave tube specifically designed for the collection and preservation of CTCs for CellSearch® analysis 1 EDTA tube for PBMCs isolation and circulating immune cells study (5mL), 2 EDTA tubes and 1 dry tube (15mL) for the preparation of the biobank (serum, plasma and cell).

Other Names:

Blood sample

Outcome Measures

Primary Outcome Measures

Percentage of patients with CTCs-PD-L1+ by CellSearch® technique [At inclusion]
A CTC is being defined as: EpCAM(+)/PanCK(+)/Dapi(+)/CD45(-). The PD-L1 status will be observed only on these cells. CTC-PD-L1- = 0 vs CTC-PD-L1+ ≥1

Secondary Outcome Measures

Number of CTCs-PD-L1+ measured by CellSearch® technique [At inclusion]
0 vs. 1 vs. 2-3 vs. 4 vs. ≥5
Presence of CTCs at inclusion by CellSearch® technique [At inclusion]
Percentage of patients with CTCs
Number of CTCs measured by CellSearch® technique [At inclusion]
0 vs 1 vs 2-3 vs 4 vs ≥5
Immune profiling [24 month follow up]
FACS study of immune system cells (T cells, NK cells, B cells, macrophages, immune-checkpoint and platelets)
Expression of PD-L1 by immuno-histochemical analysis of tissue samples [At inclusion]
PD-L1 expression on biopsy or surgical specimen previously preserved in the Montpellier University Hospital tumor library
Tumor control defined by mRECIST criteria [24 month follow up]
Best response: complete response + partial response + stable vs progression
Tumor control defined by RECIST criteria [24 month follow up]
Best response: complete response + partial response + stable vs progression
Overall Survival [24 month follow-up]
Time from immunotherapy start date to date of death from any cause
Progression Free Survival [24 month follow-up]
Time from immunotherapy start date to date of first progression or date of death from any cause

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Patients of at least 18 years old,
Patients with advanced hepatocellular carcinoma or HCC with indication for first-line PD-1 or PD-L1 immunotherapy in MDT, without prior systemic therapy,
The diagnosis of HCC is established according to imaging criteria (LI-RADSv2018 criteria) or after histological evidence,
Advanced HCC defined by BCLC stages B and C,
Patients with oral consent.

Exclusion Criteria:

Administration of a previous systemic anti-tumor treatment (immunotherapy or chemotherapy or targeted therapy)
No personal history of neoplasia in the previous 5 years
No personal history of systemic inflammatory diseases
No immunosuppressive treatment or treatment that could modify immunity (anti-TNF...)
No affiliation or non-beneficiary of a Social Security system;
Vulnerable persons according to article L1121-6 of the CSP ;
Persons of full age who are protected or unable to give their consent according to article L1121-8 of the CSP;
Pregnant or breastfeeding women according to article L1121-5 of the CSP.
Non-inclusion due to follow-up difficulties (transfer, insufficient motivation, poor compliance, priority associated pathology in care, etc.)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University Hospital, Montpellier

Investigators

Study Director: Catherine Alix-Panabières, Ph.D., University Hospital, Montpellier
Principal Investigator: Thomas Bardol, M.D., University Hospital, Montpellier