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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06355700
Other study ID # 5476
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
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
Health authority
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

Study Design


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
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