Liver Cancer and Immunotherapy in the Liquid Biopsy Era (LILIPSY)

July 7, 2025 updated by: University Hospital, Montpellier

Liver Cancer and Immunotherapy : Clinical Relevance of LIquid BioPSY

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Montpellier, France
        • Recruiting
        • CHU Montpellier
        • Contact:
          • Thomas BARDOL, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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.)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients with CTCs-PD-L1+ by CellSearch® technique
Time Frame: 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
At inclusion

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Montpellier

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 28, 2023

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

May 1, 2027

Study Registration Dates

First Submitted

March 30, 2023

First Submitted That Met QC Criteria

March 30, 2023

First Posted (Actual)

April 12, 2023

Study Record Updates

Last Update Posted (Actual)

July 10, 2025

Last Update Submitted That Met QC Criteria

July 7, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RECHMPL22_0514

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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