An Exosome-Based Liquid Biopsy for the Differential Diagnosis of Primary Liver Cancer

NCT06342414 | Recruiting

• 1 other identifier: 23228/ELUCIDATE
• Study Type: observational
• Target: 400
• Locations: 2 countries
• Sites: 5

Brief Summary

It is sometimes difficult to precisely understand whether a primary liver cancer is a hepatocellular carcinoma or a cholangiocarcinoma. The researchers will develop and validate a liquid biopsy, based on exosomal content analysis and powered by machine learning, to help clinicians differentiate these two cancers before surgery.

Conditions

Hepatocellular Carcinoma; Intrahepatic Cholangiocarcinoma; Cholangiocarcinoma; Primary Liver Cancer; Primary Liver Carcinoma; Hepatic Cancer; Hepatic Carcinoma

Keywords

Exosome; micro RNA; Differential Diagnosis

Outcome Measures

Primary Outcomes (1)

• Sensitivity

  True Positive Rate: the probability of a positive test result, conditioned on the individual truly being positive

  Through study completion, an average of 1 year

Secondary Outcomes (2)

• Specificity

  Through study completion, an average of 1 year

• Proportion of correct predictions (true positives and true negatives) among the total number of cases (i.e., accuracy)

  Through study completion, an average of 1 year

Study Arms (4)

Hepatocellular Carcinoma (Training)

A cohort of patients with histologically confirmed hepatocellular carcinoma (HCC)

Diagnostic Test: ELUCIDATE

Intrahepatic Cholangiocarcinoma (Training)

A cohort of patients with histologically confirmed intrahepatic cholangiocarcinoma (ICC)

Diagnostic Test: ELUCIDATE

Hepatocellular Carcinoma (Validation)

A cohort of patients with histologically confirmed hepatocellular carcinoma (HCC)

Diagnostic Test: ELUCIDATE

Intrahepatic Cholangiocarcinoma (Validation)

A cohort of patients with histologically confirmed intrahepatic cholangiocarcinoma (ICC)

Diagnostic Test: ELUCIDATE

Interventions

ELUCIDATE DIAGNOSTIC_TEST

ELUCIDATE (Evaluation of Liver Cholangiocarcinoma Intrahepatic)

Also known as: ELUCIDATE (Evaluation of Liver Cholangiocarcinoma Intrahepatic)

Hepatocellular Carcinoma (Training); Hepatocellular Carcinoma (Validation); Intrahepatic Cholangiocarcinoma (Training); Intrahepatic Cholangiocarcinoma (Validation)

Eligibility Criteria

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

Study Population

Individuals who were diagnosed with either intrahepatic cholangiocarcinoma or hepatocellular carcinoma (case-case design for a differential diagnosis study)

You may qualify if:

• A histologically confirmed diagnosis of hepatocellular carcinoma
• A histologically confirmed diagnosis of intrahepatic cholangiocarcinoma
• Received standard diagnostic and staging procedures as per local guidelines
• Availability of at least one blood-derived sample, drawn before receiving any curative-intent treatment

You may not qualify if:

• Lack of or inability to provide informed consent
• Synchronous hepatocellular carcinoma and intrahepatic cholangiocarcinoma
• Primary liver cancer other than hepatocellular carcinoma or intrahepatic cholangiocarcinoma
• Secondary liver cancer

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (5)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Graduate School of Medical Sciences, Kyushu University

Fukuoka, Japan

RECRUITING

Graduate School of Medical Sciences, Kumamoto University

Kumamoto, Japan

RECRUITING

Hokkaido University Graduate School of Medicine

Sapporo, Japan

RECRUITING

Tokushima University

Tokushima, Japan

RECRUITING

Related Publications (18)

• Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, Roberts LR, Heimbach JK. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018 Aug;68(2):723-750. doi: 10.1002/hep.29913. No abstract available.

  PMID: 29624699 BACKGROUND

• Wu Y, Xia C, Chen J, Qin Q, Ye Z, Song B. Diagnostic performance of magnetic resonance imaging and contrast-enhanced ultrasound in differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma: a meta-analysis. Abdom Radiol (NY). 2024 Jan;49(1):34-48. doi: 10.1007/s00261-023-04064-z. Epub 2023 Oct 12.

  PMID: 37823913 BACKGROUND

• El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008 May;134(6):1752-63. doi: 10.1053/j.gastro.2008.02.090.

  PMID: 18471552 BACKGROUND

• Vigano L, Lleo A, Muglia R, Gennaro N, Sama L, Colapietro F, Roncalli M, Aghemo A, Chiti A, Di Tommaso L, Solbiati L, Colombo M, Torzilli G. Intrahepatic cholangiocellular carcinoma with radiological enhancement patterns mimicking hepatocellular carcinoma. Updates Surg. 2020 Jun;72(2):413-421. doi: 10.1007/s13304-020-00750-5. Epub 2020 Apr 22.

  PMID: 32323164 BACKGROUND

• Kovac JD, Jankovic A, Dikic-Rom A, Grubor N, Antic A, Dugalic V. Imaging Spectrum of Intrahepatic Mass-Forming Cholangiocarcinoma and Its Mimickers: How to Differentiate Them Using MRI. Curr Oncol. 2022 Jan 30;29(2):698-723. doi: 10.3390/curroncol29020061.

  PMID: 35200560 BACKGROUND

• Arbelaiz A, Azkargorta M, Krawczyk M, Santos-Laso A, Lapitz A, Perugorria MJ, Erice O, Gonzalez E, Jimenez-Aguero R, Lacasta A, Ibarra C, Sanchez-Campos A, Jimeno JP, Lammert F, Milkiewicz P, Marzioni M, Macias RIR, Marin JJG, Patel T, Gores GJ, Martinez I, Elortza F, Falcon-Perez JM, Bujanda L, Banales JM. Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma. Hepatology. 2017 Oct;66(4):1125-1143. doi: 10.1002/hep.29291. Epub 2017 Aug 26.

  PMID: 28555885 BACKGROUND

• Banales JM, Inarrairaegui M, Arbelaiz A, Milkiewicz P, Muntane J, Munoz-Bellvis L, La Casta A, Gonzalez LM, Arretxe E, Alonso C, Martinez-Arranz I, Lapitz A, Santos-Laso A, Avila MA, Martinez-Chantar ML, Bujanda L, Marin JJG, Sangro B, Macias RIR. Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis. Hepatology. 2019 Aug;70(2):547-562. doi: 10.1002/hep.30319. Epub 2019 Feb 14.

  PMID: 30325540 BACKGROUND

• Huang C, Xu X, Wang M, Xiao X, Cheng C, Ji J, Fang M, Gao C. Serum N-glycan fingerprint helps to discriminate intrahepatic cholangiocarcinoma from hepatocellular carcinoma. Electrophoresis. 2021 Jun;42(11):1187-1195. doi: 10.1002/elps.202000392. Epub 2021 Mar 1.

  PMID: 33570803 BACKGROUND

• Chen VL, Xu D, Wicha MS, Lok AS, Parikh ND. Utility of Liquid Biopsy Analysis in Detection of Hepatocellular Carcinoma, Determination of Prognosis, and Disease Monitoring: A Systematic Review. Clin Gastroenterol Hepatol. 2020 Dec;18(13):2879-2902.e9. doi: 10.1016/j.cgh.2020.04.019. Epub 2020 Apr 11.

  PMID: 32289533 BACKGROUND

• Foda ZH, Annapragada AV, Boyapati K, Bruhm DC, Vulpescu NA, Medina JE, Mathios D, Cristiano S, Niknafs N, Luu HT, Goggins MG, Anders RA, Sun J, Meta SH, Thomas DL, Kirk GD, Adleff V, Phallen J, Scharpf RB, Kim AK, Velculescu VE. Detecting Liver Cancer Using Cell-Free DNA Fragmentomes. Cancer Discov. 2023 Mar 1;13(3):616-631. doi: 10.1158/2159-8290.CD-22-0659.

  PMID: 36399356 BACKGROUND

• Lapitz A, Azkargorta M, Milkiewicz P, Olaizola P, Zhuravleva E, Grimsrud MM, Schramm C, Arbelaiz A, O'Rourke CJ, La Casta A, Milkiewicz M, Pastor T, Vesterhus M, Jimenez-Aguero R, Dill MT, Lamarca A, Valle JW, Macias RIR, Izquierdo-Sanchez L, Perez Castano Y, Caballero-Camino FJ, Riano I, Krawczyk M, Ibarra C, Bustamante J, Nova-Camacho LM, Falcon-Perez JM, Elortza F, Perugorria MJ, Andersen JB, Bujanda L, Karlsen TH, Folseraas T, Rodrigues PM, Banales JM. Liquid biopsy-based protein biomarkers for risk prediction, early diagnosis, and prognostication of cholangiocarcinoma. J Hepatol. 2023 Jul;79(1):93-108. doi: 10.1016/j.jhep.2023.02.027. Epub 2023 Mar 1.

  PMID: 36868481 BACKGROUND

• Wang P, Song Q, Ren J, Zhang W, Wang Y, Zhou L, Wang D, Chen K, Jiang L, Zhang B, Chen W, Qu C, Zhao H, Jiao Y. Simultaneous analysis of mutations and methylations in circulating cell-free DNA for hepatocellular carcinoma detection. Sci Transl Med. 2022 Nov 23;14(672):eabp8704. doi: 10.1126/scitranslmed.abp8704. Epub 2022 Nov 23.

  PMID: 36417488 BACKGROUND

• Ye Q, Ling S, Zheng S, Xu X. Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA. Mol Cancer. 2019 Jul 3;18(1):114. doi: 10.1186/s12943-019-1043-x.

  PMID: 31269959 BACKGROUND

• Li S, Yao J, Xie M, Liu Y, Zheng M. Exosomal miRNAs in hepatocellular carcinoma development and clinical responses. J Hematol Oncol. 2018 Apr 11;11(1):54. doi: 10.1186/s13045-018-0579-3.

  PMID: 29642941 BACKGROUND

• Sasaki R, Kanda T, Yokosuka O, Kato N, Matsuoka S, Moriyama M. Exosomes and Hepatocellular Carcinoma: From Bench to Bedside. Int J Mol Sci. 2019 Mar 20;20(6):1406. doi: 10.3390/ijms20061406.

  PMID: 30897788 BACKGROUND

• Wang M, Gao Y, Feng H, Warner E, An M, Jia J, Chen S, Fang M, Ji J, Gu X, Gao C. A nomogram incorporating six easily obtained parameters to discriminate intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Cancer Med. 2018 Mar;7(3):646-654. doi: 10.1002/cam4.1341. Epub 2018 Feb 23.

  PMID: 29473340 BACKGROUND

• Si YQ, Wang XQ, Pan CC, Wang Y, Lu ZM. An Efficient Nomogram for Discriminating Intrahepatic Cholangiocarcinoma From Hepatocellular Carcinoma: A Retrospective Study. Front Oncol. 2022 Apr 11;12:833999. doi: 10.3389/fonc.2022.833999. eCollection 2022.

  PMID: 35480111 BACKGROUND

• Wang Y, Zhang C, Zhang P, Guo G, Jiang T, Zhao X, Jiang J, Huang X, Tong H, Tian Y. Serum exosomal microRNAs combined with alpha-fetoprotein as diagnostic markers of hepatocellular carcinoma. Cancer Med. 2018 May;7(5):1670-1679. doi: 10.1002/cam4.1390. Epub 2018 Mar 23.

  PMID: 29573235 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Cholangiocarcinoma; Liver Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Ajay Goel, PhD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ajay Goel, PhD

CONTACT

6262183452; AJGOEL@COH.ORG

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2024
• First Posted: April 2, 2024
• Study Start: March 15, 2024
• Primary Completion (Estimated): June 18, 2026
• Study Completion (Estimated): June 18, 2026
• Last Updated: April 2, 2025

Record last verified: 2025-04

Locations

JP (4); US (1)