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.
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
- Conditions the study is for
- Hepatocellular Carcinoma, BCLC Stage B Hepatocellular Carcinoma, BCLC Stage C Hepatocellular Carcinoma
- 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
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 ;
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- 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.
France1 site, 1 recruiting
- Recruiting
CHU Montpellier
Montpellier
Thomas BARDOL, M.D.
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).
- Conditions
- Hepatocellular Carcinoma, BCLC Stage B Hepatocellular Carcinoma, BCLC Stage C Hepatocellular Carcinoma, Immune Checkpoint Inhibitor, Liquid Biopsy
- 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 group | Role | What they receive |
|---|---|---|
| BCLC B and C HCC patients | Experimental | 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. Receives: Biological: Liquid Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Number of CTCs-PD-L1+ measured by CellSearch® technique
0 vs. 1 vs. 2-3 vs. 4 vs. ≥5
Measured: At inclusion
Presence of CTCs at inclusion by CellSearch® technique
Percentage of patients with CTCs
Measured: At inclusion
Number of CTCs measured by CellSearch® technique
0 vs 1 vs 2-3 vs 4 vs ≥5
Measured: At inclusion
Immune profiling
FACS study of immune system cells (T cells, NK cells, B cells, macrophages, immune-checkpoint and platelets)
Measured: 24 month follow up
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
Tumor control defined by mRECIST criteria
Best response: complete response + partial response + stable vs progression
Measured: 24 month follow up
Tumor control defined by RECIST criteria
Best response: complete response + partial response + stable vs progression
Measured: 24 month follow up
Overall Survival
Time from immunotherapy start date to date of death from any cause
Measured: 24 month follow-up
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.
- First posted12 Apr 2023
- Study start28 Jun 2023
- Primary completionDec 2026 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Catherine Alix-Panabières, Ph.D., Study director, University Hospital, MontpellierThomas Bardol, M.D., Principal investigator, University Hospital, Montpellier
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 28397823Meng 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 15623589Leone 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 30200242Alix-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 33811121Alix-Panabieres C. The future of liquid biopsy. Nature. 2020 Mar;579(7800):S9. doi: 10.1038/d41586-020-00844-5. No abstract available.
PubMed 32214259Eslami-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 32850309Mego 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 27326253Ye 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 29434410Mazel 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 26093818Bergmann 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 32391189Darga 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 34780566Strati 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 28838214Jacot 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 32712650Sinoquet 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 34355741European 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