Clinical trial NCT06929845: Organoid Models of Hepatocellular Carcinoma
Official title: Organoid Models of Hepatocellular Carcinoma to Test Treatment Efficacy, Exploring Correlations With Tumor Microenvironment and Gut-liver-tumor Axis.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hepatocellular Carcinoma
Organoids
Gut Microbiota
Tumor Microenvironment
System Disorders, Digestive
Surgery
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2025-04-16
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A promising tool to elucidate the molecular characteristics of HCC are patient-derived organoids (PDOs), three-dimensional cultures of cells that self-organise according to tissue-specific patterns and can be used to test the susceptibility of a specific tumour to anticancer agents. In this study, PDOs for HCC will be developed that closely resemble the tumour microenvironment in vivo and mimic the crosstalk of the gut-liver axis to establish a correlation with patient prognosis and test the efficacy of available systemic therapies.

Detailed description: The objectives of the project will be 1) to develop HCC PDOs from tumour and non-tumour patient liver tissue obtained from surgical specimens or liver biopsies; 2) to evaluate genomic and transcriptomic changes resulting from the integration of HCC PDOs with patient-derived gut microbiota and host immune cells, and to assess the correlation with patient prognosis; 3) to exploit HCC PDOs to test the efficacy of systemic therapies (ICI and TKIs) and to understand possible modifying cofactors.

Researchers with laboratory experience have been recruited who will focus on the construction of PDOs and the analysis of immune-inflammatory pathways. State-of-the-art technologies will be used, in particular next-generation sequencing, flow cytometry, high-throughput genomic and transcriptomic analysis, ultrafiltration, drug screening, multiplex immunoassays and enzyme immunoassays. The project aims to study the mechanisms involved in the modulation of therapeutic efficacy in patients with HCC. Therefore, the experimental model could be a valuable support to be integrated into real clinical practice to maximise therapeutic efficacy through a fully customised strategy.

Eligibility criteria: Inclusion Criteria:

* Capacity to express informed consent;
* Age ≥18 years;
* Suspected radiological diagnosis of HCC or diagnosis of HCC with indications for surgical resection.

Exclusion Criteria:

* Age \< 18 years;
* Contraindications to liver biopsy (ascites, platelets\<50,000, INR\>1.7);
* Contraindications to HCC resection surgery;
* Active viral infection;
* Refusal to sign informed consent to participate in the study.

Primary outcomes:
measure: Organoid model development
timeFrame: 2-18 months
Secondary outcomes:
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC CEMAD, Largo A. Gemelli, 8
Study officials:
affiliation: Fondazione Policlinico A. Gemelli IRCCS, Rome, Largo A. Gemelli, 8
name: Francesca Romana Ponziani, PI
role: PRINCIPAL_INVESTIGATOR
References: