Clinical trial NCT06355700: Hepatocellular Carcinoma Liver Organoids
Official title: Hepatocellular Carcinoma Organoids to Explore Tumor Microenvironment and Test Treatment Efficacy - Hepatocellular Carcinoma Liver Organoids (HELIO)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hepatocellular Carcinoma
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2024-04-09
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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


Eligibility criteria: 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

Primary outcomes:
measure: Success rate of hepatocellular carcinoma organoids integrated with host gut microbiota and peripheral blood mononuclear cells
timeFrame: within 12 months
Secondary outcomes:
measure: Analysis of hepatocellular carcinoma organoid transcriptome distribution within a reference set from The Cancer Genome Atlas
timeFrame: within 12 months
measure: Evaluation of the concordance of somatic genetic mutations between the organoid and the original tumor
timeFrame: within 12 months
measure: Correlation between gut microbiota community profiling and growth rate of hepatocellular carcinoma organoids
timeFrame: within 12 months
measure: Treatment response evaluation in vitro
timeFrame: Day 5
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Fondazione Policlinico Agostino Gemelli IRCCS
Study officials:
References:
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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.
citation: 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.
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.
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.