Hepatocellular Carcinoma Liver Organoids

Hepatocellular Carcinoma Clinical Trial

— HELIO  

Official title:

Hepatocellular Carcinoma Organoids to Explore Tumor Microenvironment and Test Treatment Efficacy - Hepatocellular Carcinoma Liver Organoids (HELIO)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06355700
• Other study ID #: 5476
• Status: Recruiting
• Phase: N/A
• Start date: June 15, 2023
• Est. completion date: March 2025

Study information

• Verified date: March 2024
• Source: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this interventional study is to create hepatocellular carcinoma organoids from liver bioptic samples of individuals with hepatocellular carcinoma. The main questions it aims to answer are:

• the feasibility of hepatocellular carcinoma organoids integrated with host gut microbiota and peripheral blood mononuclear cells

• the molecular pattern of the organoid tumor microenvironment

• the in vitro therapeutic response of hepatocellular carcinoma organoids

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Ability to express informed consent

• Patients = 18 years of age

• Radiological diagnosis of hepatocellular carcinoma (HCC)

Exclusion Criteria:

• Patients <18 years of age

• Contraindications for liver biopsy: ascites, platelet count <50.000, International Normalized Ratio (INR) >1.7

• Active viral infection

• Refusal to give informed consent for the study

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Procedure:
• Liver biopsy
The liver biopsy is ultrasound-guided and target the hepatic lesions. It is performed with 18G or 19G Menghini needle. A part of bioptic sample will be used for genomic analysis. An other part of sample will be cultured to create the organoid. The organoid's cultures will be integrated with the host gut microbiota (collected by a fecal sample) and peripheral blood mononuclear cells (from venous blood sample) and they will be used for research such as molecular analysis and pharmacological tests.

Locations

Country	Name	City	State
Italy	Fondazione Policlinico Agostino Gemelli IRCCS	Roma

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Broutier L, Mastrogiovanni G, Verstegen MM, Francies HE, Gavarro LM, Bradshaw CR, Allen GE, Arnes-Benito R, Sidorova O, Gaspersz MP, Georgakopoulos N, Koo BK, Dietmann S, Davies SE, Praseedom RK, Lieshout R, IJzermans JNM, Wigmore SJ, Saeb-Parsy K, Garnett MJ, van der Laan LJ, Huch M. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med. 2017 Dec;23(12):1424-1435. doi: 10.1038/nm.4438. Epub 2017 Nov 13. — View Citation

Huch M, Koo BK. Modeling mouse and human development using organoid cultures. Development. 2015 Sep 15;142(18):3113-25. doi: 10.1242/dev.118570. — View Citation

Kretzschmar K. Cancer research using organoid technology. J Mol Med (Berl). 2021 Apr;99(4):501-515. doi: 10.1007/s00109-020-01990-z. Epub 2020 Oct 14. — View Citation

Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, Lencioni R, Koike K, Zucman-Rossi J, Finn RS. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021 Jan 21;7(1):6. doi: 10.1038/s41572-020-00240-3. Erratum In: Nat Rev Dis Primers. 2024 Feb 12;10(1):10. — View Citation

Nuciforo S, Fofana I, Matter MS, Blumer T, Calabrese D, Boldanova T, Piscuoglio S, Wieland S, Ringnalda F, Schwank G, Terracciano LM, Ng CKY, Heim MH. Organoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies. Cell Rep. 2018 Jul 31;24(5):1363-1376. doi: 10.1016/j.celrep.2018.07.001. — View Citation

Ponziani FR, Bhoori S, Castelli C, Putignani L, Rivoltini L, Del Chierico F, Sanguinetti M, Morelli D, Paroni Sterbini F, Petito V, Reddel S, Calvani R, Camisaschi C, Picca A, Tuccitto A, Gasbarrini A, Pompili M, Mazzaferro V. Hepatocellular Carcinoma Is Associated With Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease. Hepatology. 2019 Jan;69(1):107-120. doi: 10.1002/hep.30036. Epub 2018 Jul 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Success rate of hepatocellular carcinoma organoids integrated with host gut microbiota and peripheral blood mononuclear cells	Number of successfully created organoids from all hepatocellular carcinoma samples	within 12 months
Secondary	Analysis of hepatocellular carcinoma organoid transcriptome distribution within a reference set from The Cancer Genome Atlas	Comparison between organoids transcriptome and data from The Cancer Genome Atlas	within 12 months
Secondary	Evaluation of the concordance of somatic genetic mutations between the organoid and the original tumor	DNA organoids and original tumor sample sequencing and comparison between the somatic genetic mutations found in both models	within 12 months
Secondary	Correlation between gut microbiota community profiling and growth rate of hepatocellular carcinoma organoids	Definition of microbiota composition via DNA and RNA sequencing and correlation between specific bacteria abundance and successful organoids growth	within 12 months
Secondary	Treatment response evaluation in vitro	Evaluation of organoids' tumor cells survival after 5 days of chemotherapy treatment.; Treatment will include different concentrations of sorafenib, lenvatinib, atezolizumab, bevacizumab, tremelimumab, durvalumab, regorafenib, cabozantinib. Tumor cells vitality will be assessed trough Cell TitelGlo3D Cell Viability Assay.	Day 5