Hepatocellular Carcinoma Liver Organoids

NCT06355700 | Recruiting

• 1 other identifier: 5476
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Analysis of hepatocellular carcinoma organoid transcriptome distribution within a reference set from The Cancer Genome Atlas

  within 12 months

• Evaluation of the concordance of somatic genetic mutations between the organoid and the original tumor

  within 12 months

• Correlation between gut microbiota community profiling and growth rate of hepatocellular carcinoma organoids

  within 12 months

• Treatment response evaluation in vitro

  Day 5

Study Arms (1)

Hepatocellular Carcinoma

EXPERIMENTAL

Participants undergo to a liver biopsy, a venous blood sampling and a fecal sample collecting

Procedure: Liver biopsy

Interventions

Liver biopsy PROCEDURE

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.

Hepatocellular Carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to express informed consent
• Patients ≥ 18 years of age
• Radiological diagnosis of hepatocellular carcinoma (HCC)

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Agostino Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

Related Publications (6)

• 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.

  PMID: 33479224 BACKGROUND

• 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.

  PMID: 26395140 BACKGROUND

• 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.

  PMID: 33057820 BACKGROUND

• 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.

  PMID: 29131160 BACKGROUND

• 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.

  PMID: 30067989 BACKGROUND

• 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.

  PMID: 29665135 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: April 9, 2024
• Study Start: June 15, 2023
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: April 9, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)