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Hepatocellular CarcinomaLILIPSYNCT05810402

Liver Cancer and Immunotherapy in the Liquid Biopsy Era

A study testing Liquid Biopsy in people with Hepatocellular Carcinoma and BCLC Stage B Hepatocellular Carcinoma, run by University Hospital, Montpellier at 1 site in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
What is being tested?
Liquid Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteFrance
Study dates
28 Jun 2023to May 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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 ;
Show all 9Show fewer
  • 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.)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Thomas Bardol, M.D. contact

+33682882757

t-bardol@chu-montpellier.fr

Catherine Guillemare contact

+33467332304

c-guillemare@chu-montpellier.fr

France1 site, 1 recruiting

  • CHU Montpellier

    Montpellier

    Thomas BARDOL, M.D.

    Recruiting

Other trials in France

About this study

Official title: 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.

Read the 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).

Being tested
Liquid Biopsy
Keywords
Hepatocellular Carcinoma, BCLC Stage B and C, Immune Checkpoint Inhibitor, Liquid Biopsy, Precision Medicine
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Liquid BiopsyBiological

    Also called Blood sample

    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).
Study groups in NCT05810402
Study groupRoleWhat they receive
BCLC B and C HCC patientsExperimentalFor 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.
Receives: Biological: Liquid Biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of patients with CTCs-PD-L1+ by CellSearch® technique

    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

    Measured: At inclusion

Secondary outcomes (9)

  1. Number of CTCs-PD-L1+ measured by CellSearch® technique

    0 vs. 1 vs. 2-3 vs. 4 vs. ≥5

    Measured: At inclusion

  2. Presence of CTCs at inclusion by CellSearch® technique

    Percentage of patients with CTCs

    Measured: At inclusion

  3. Number of CTCs measured by CellSearch® technique

    0 vs 1 vs 2-3 vs 4 vs ≥5

    Measured: At inclusion

  4. Immune profiling

    FACS study of immune system cells (T cells, NK cells, B cells, macrophages, immune-checkpoint and platelets)

    Measured: 24 month follow up

  5. Expression of PD-L1 by immuno-histochemical analysis of tissue samples

    PD-L1 expression on biopsy or surgical specimen previously preserved in the Montpellier University Hospital tumor library

    Measured: At inclusion

  6. Tumor control defined by mRECIST criteria

    Best response: complete response + partial response + stable vs progression

    Measured: 24 month follow up

  7. Tumor control defined by RECIST criteria

    Best response: complete response + partial response + stable vs progression

    Measured: 24 month follow up

  8. Overall Survival

    Time from immunotherapy start date to date of death from any cause

    Measured: 24 month follow-up

  9. Progression Free Survival

    Time from immunotherapy start date to date of first progression or date of death from any cause

    Measured: 24 month follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Apr 2023
  2. Study start28 Jun 2023
  3. Primary completionDec 2026 (estimated)
  4. Study completionMay 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Model description
Homogenous cohort of BCLC Stage B and C hepatocellular carcinoma patients that will undergo immunotherapy +/- anti-angiogenic agent (bevacizumab)
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05810402
Sponsor's protocol ID
RECHMPL22_0514
Acronym
LILIPSY
Status last verified
Jul 2025
First submitted
30 Mar 2023
Last updated
10 Jul 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Pantel K, Alix-Panabieres C. Tumour microenvironment: informing on minimal residual disease in solid tumours. Nat Rev Clin Oncol. 2017 Jun;14(6):325-326. doi: 10.1038/nrclinonc.2017.53. Epub 2017 Apr 11. No abstract available.

    PubMed 28397823

  • Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, Beitsch PD, Leitch M, Hoover S, Euhus D, Haley B, Morrison L, Fleming TP, Herlyn D, Terstappen LW, Fehm T, Tucker TF, Lane N, Wang J, Uhr JW. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res. 2004 Dec 15;10(24):8152-62. doi: 10.1158/1078-0432.CCR-04-1110.

    PubMed 15623589

  • Leone K, Poggiana C, Zamarchi R. The Interplay between Circulating Tumor Cells and the Immune System: From Immune Escape to Cancer Immunotherapy. Diagnostics (Basel). 2018 Aug 30;8(3):59. doi: 10.3390/diagnostics8030059.

    PubMed 30200242

  • Alix-Panabieres C, Pantel K. Liquid Biopsy: From Discovery to Clinical Application. Cancer Discov. 2021 Apr;11(4):858-873. doi: 10.1158/2159-8290.CD-20-1311.

    PubMed 33811121

  • Alix-Panabieres C. The future of liquid biopsy. Nature. 2020 Mar;579(7800):S9. doi: 10.1038/d41586-020-00844-5. No abstract available.

    PubMed 32214259

  • Eslami-S Z, Cortes-Hernandez LE, Alix-Panabieres C. The Metastatic Cascade as the Basis for Liquid Biopsy Development. Front Oncol. 2020 Jul 21;10:1055. doi: 10.3389/fonc.2020.01055. eCollection 2020.

    PubMed 32850309

  • Mego M, Gao H, Cohen EN, Anfossi S, Giordano A, Sanda T, Fouad TM, De Giorgi U, Giuliano M, Woodward WA, Alvarez RH, Valero V, Ueno NT, Hortobagyi GN, Cristofanilli M, Reuben JM. Circulating Tumor Cells (CTC) Are Associated with Defects in Adaptive Immunity in Patients with Inflammatory Breast Cancer. J Cancer. 2016 Jun 3;7(9):1095-104. doi: 10.7150/jca.13098. eCollection 2016.

    PubMed 27326253

  • Ye L, Zhang F, Li H, Yang L, Lv T, Gu W, Song Y. Circulating Tumor Cells Were Associated with the Number of T Lymphocyte Subsets and NK Cells in Peripheral Blood in Advanced Non-Small-Cell Lung Cancer. Dis Markers. 2017;2017:5727815. doi: 10.1155/2017/5727815. Epub 2017 Dec 24.

    PubMed 29434410

  • Mazel M, Jacot W, Pantel K, Bartkowiak K, Topart D, Cayrefourcq L, Rossille D, Maudelonde T, Fest T, Alix-Panabieres C. Frequent expression of PD-L1 on circulating breast cancer cells. Mol Oncol. 2015 Nov;9(9):1773-82. doi: 10.1016/j.molonc.2015.05.009. Epub 2015 Jun 9.

    PubMed 26093818

  • Bergmann S, Coym A, Ott L, Soave A, Rink M, Janning M, Stoupiec M, Coith C, Peine S, von Amsberg G, Pantel K, Riethdorf S. Evaluation of PD-L1 expression on circulating tumor cells (CTCs) in patients with advanced urothelial carcinoma (UC). Oncoimmunology. 2020 Mar 23;9(1):1738798. doi: 10.1080/2162402X.2020.1738798. eCollection 2020.

    PubMed 32391189

  • Darga EP, Dolce EM, Fang F, Kidwell KM, Gersch CL, Kregel S, Thomas DG, Gill A, Brown ME, Gross S, Connelly M, Holinstat M, Cobain EF, Rae JM, Hayes DF, Paoletti C. PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer. PLoS One. 2021 Nov 15;16(11):e0260124. doi: 10.1371/journal.pone.0260124. eCollection 2021.

    PubMed 34780566

  • Strati A, Koutsodontis G, Papaxoinis G, Angelidis I, Zavridou M, Economopoulou P, Kotsantis I, Avgeris M, Mazel M, Perisanidis C, Sasaki C, Alix-Panabieres C, Lianidou E, Psyrri A. Prognostic significance of PD-L1 expression on circulating tumor cells in patients with head and neck squamous cell carcinoma. Ann Oncol. 2017 Aug 1;28(8):1923-1933. doi: 10.1093/annonc/mdx206.

    PubMed 28838214

  • Jacot W, Mazel M, Mollevi C, Pouderoux S, D'Hondt V, Cayrefourcq L, Bourgier C, Boissiere-Michot F, Berrabah F, Lopez-Crapez E, Bidard FC, Viala M, Maudelonde T, Guiu S, Alix-Panabieres C. Clinical Correlations of Programmed Cell Death Ligand 1 Status in Liquid and Standard Biopsies in Breast Cancer. Clin Chem. 2020 Aug 1;66(8):1093-1101. doi: 10.1093/clinchem/hvaa121.

    PubMed 32712650

  • Sinoquet L, Jacot W, Gauthier L, Pouderoux S, Viala M, Cayrefourcq L, Quantin X, Alix-Panabieres C. Programmed Cell Death Ligand 1-Expressing Circulating Tumor Cells: A New Prognostic Biomarker in Non-Small Cell Lung Cancer. Clin Chem. 2021 Nov 1;67(11):1503-1512. doi: 10.1093/clinchem/hvab131.

    PubMed 34355741

  • European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012 Apr;56(4):908-43. doi: 10.1016/j.jhep.2011.12.001. No abstract available.

    PubMed 22424438

Questions about this trial

What is this clinical trial studying?

A study testing Liquid Biopsy in people with Hepatocellular Carcinoma and BCLC Stage B Hepatocellular Carcinoma, run by University Hospital, Montpellier at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Thomas Bardol, M.D. (+33682882757, t-bardol@chu-montpellier.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of patients with CTCs-PD-L1+ by CellSearch® technique (time frame: At inclusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05810402, which also lists 25 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2025.

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