Exosome-derived Extrahepatic Metastasis Detection By Liquid Biopsy In Colorectal Cancer Liver Metastases

NCT07224724 | Recruiting

• 1 other identifier: 23228/EXELION
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer is the third most common malignancy worldwide, and prognosis largely depends on how effectively metastatic disease is managed. The liver is the most frequent and prognostically important site of metastasis, and patients responding well to chemotherapy may become candidates for curative hepatic resection. However, the presence of extrahepatic metastasis (EHM) critically influences treatment eligibility and survival. Although clinical scores such as the Fong and Beppu systems include EHM as a determinant, its detection by imaging remains limited, especially for small or occult lesions. Accurate identification of EHM is also essential when considering liver transplantation for unresectable colorectal liver metastases (CRLM), where EHM remains an exclusion criterion. The EXELION Study aims to develop a non-invasive diagnostic model using serum exosomal microRNAs (miRNAs) to detect both hepatic and extrahepatic metastases in patients with CRLM. By integrating circulating miRNA profiling with machine learning-based analysis, this study seeks to supplement imaging diagnostics, improve treatment stratification, and enhance clinical decision-making for metastatic colorectal cancer.

Conditions

Colorectal Cancer Liver Metastases (CRLM); Metastatic Colorectal Carcinoma (mCRC)

Keywords

CRC; Extrahepatic metastasis; liquid biopsy; Early detection

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

• Accuracy

  Through study completion, an average of 1 year

Study Arms (6)

Extrahepatic liver metastasis patients(Discovery Cohort)

Patients with colorectal liver metastases (CRLM) who have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the first (discovery) cohort.

Non-extrahepatic liver metastasis patients(Discovery Cohort)

Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who do not have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the first (discovery) cohort.

Other: EXELION

Extrahepatic liver metastasis patients(Training Cohort)

Extrahepatic liver metastasis patients (Training Cohort) Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the first (training) cohort.

Other: EXELION

Non-extrahepatic liver metastasis patients (Training Cohort)

Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who do not have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the (training) cohort.

Other: EXELION

Extrahepatic liver metastasis patients (Validation Cohort)

Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the second, independent, validation cohort

Non-extrahepatic liver metastasis patients (Validation Cohort)

Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who do not have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the second, independent, validation cohort

Other: EXELION

Interventions

EXELION OTHER

A panel of exosomal microRNA, whose expression level is tested in serum or plasma

Extrahepatic liver metastasis patients(Training Cohort); Non-extrahepatic liver metastasis patients (Training Cohort); Non-extrahepatic liver metastasis patients (Validation Cohort); Non-extrahepatic liver metastasis patients(Discovery Cohort)

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

Patients diagnosed with colorectal liver metastases (CRLM) originating from histologically confirmed colorectal adenocarcinoma at participating institutions.

You may qualify if:

• Adults (≥18 years old)
• Histologically- or cytologically-confirmed colorectal cancer that is metastatic
• Availability of pre-treatment plasma samples
• Written informed consent provided
• Sufficient clinical and imaging data to determine presence/absence of extrahepatic metastasis

You may not qualify if:

• Prior malignancies within 5 years
• Poor sample quality or hemolysis
• Inability to provide informed consent

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Related Publications (8)

• Adam R, Piedvache C, Chiche L, Adam JP, Salame E, Bucur P, Cherqui D, Scatton O, Granger V, Ducreux M, Cillo U, Cauchy F, Mabrut JY, Verslype C, Coubeau L, Hardwigsen J, Boleslawski E, Muscari F, Jeddou H, Pezet D, Heyd B, Lucidi V, Geboes K, Lerut J, Majno P, Grimaldi L, Levi F, Lewin M, Gelli M; Collaborative TransMet group. Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): results from a multicentre, open-label, prospective, randomised controlled trial. Lancet. 2024 Sep 21;404(10458):1107-1118. doi: 10.1016/S0140-6736(24)01595-2.

  PMID: 39306468 BACKGROUND

• Giuliante F, Vigano L, De Rose AM, Mirza DF, Lapointe R, Kaiser G, Barroso E, Ferrero A, Isoniemi H, Lopez-Ben S, Popescu I, Ouellet JF, Hubert C, Regimbeau JM, Lin JK, Skipenko OG, Ardito F, Adam R. Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry. Ann Surg Oncol. 2021 Dec;28(13):8198-8208. doi: 10.1245/s10434-021-10220-w. Epub 2021 Jul 1.

  PMID: 34212254 BACKGROUND

• Carpizo DR, D'Angelica M. Liver resection for metastatic colorectal cancer in the presence of extrahepatic disease. Lancet Oncol. 2009 Aug;10(8):801-9. doi: 10.1016/S1470-2045(09)70081-6.

  PMID: 19647200 BACKGROUND

• Leung U, Gonen M, Allen PJ, Kingham TP, DeMatteo RP, Jarnagin WR, D'Angelica MI. Colorectal Cancer Liver Metastases and Concurrent Extrahepatic Disease Treated With Resection. Ann Surg. 2017 Jan;265(1):158-165. doi: 10.1097/SLA.0000000000001624.

  PMID: 28009741 BACKGROUND

• Bojmar L, Zambirinis CP, Hernandez JM, Chakraborty J, Shaashua L, Kim J, Johnson KE, Hanna S, Askan G, Burman J, Ravichandran H, Zheng J, Jolissaint JS, Srouji R, Song Y, Choubey A, Kim HS, Cioffi M, van Beek E, Sigel C, Jessurun J, Velasco Riestra P, Blomstrand H, Jonsson C, Jonsson A, Lauritzen P, Buehring W, Ararso Y, Hernandez D, Vinagolu-Baur JP, Friedman M, Glidden C, Firmenich L, Lieberman G, Mejia DL, Nasar N, Mutvei AP, Paul DM, Bram Y, Costa-Silva B, Basturk O, Boudreau N, Zhang H, Matei IR, Hoshino A, Kelsen D, Sagi I, Scherz A, Scherz-Shouval R, Yarden Y, Oren M, Egeblad M, Lewis JS, Keshari K, Grandgenett PM, Hollingsworth MA, Rajasekhar VK, Healey JH, Bjornsson B, Simeone DM, Tuveson DA, Iacobuzio-Donahue CA, Bromberg J, Vincent CT, O'Reilly EM, DeMatteo RP, Balachandran VP, D'Angelica MI, Kingham TP, Allen PJ, Simpson AL, Elemento O, Sandstrom P, Schwartz RE, Jarnagin WR, Lyden D. Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer. Nat Med. 2024 Aug;30(8):2170-2180. doi: 10.1038/s41591-024-03075-7. Epub 2024 Jun 28.

  PMID: 38942992 BACKGROUND

• Katipally RR, Martinez CA, Pugh SA, Bridgewater JA, Primrose JN, Domingo E, Maughan TS, Talamonti MS, Posner MC, Weichselbaum RR, Pitroda SP; with the S:CORT Consortium. Integrated Clinical-Molecular Classification of Colorectal Liver Metastases: A Biomarker Analysis of the Phase 3 New EPOC Randomized Clinical Trial. JAMA Oncol. 2023 Sep 1;9(9):1245-1254. doi: 10.1001/jamaoncol.2023.2535.

  PMID: 37471075 BACKGROUND

• Mekenkamp LJ, Haan JC, Koopman M, Vink-Borger ME, Israeli D, Teerenstra S, Ylstra B, Meijer GA, Punt CJ, Nagtegaal ID. Chromosome 20p11 gains are associated with liver-specific metastasis in patients with colorectal cancer. Gut. 2013 Jan;62(1):94-101. doi: 10.1136/gutjnl-2011-301587. Epub 2012 Jan 20.

  PMID: 22267596 BACKGROUND

• Mahuron KM, Hernandez MC, Wong P, Fan D, Ituarte PHG, Raoof M, Singh G, Fong Y, Melstrom LG. Liver Resection With Extrahepatic Disease: A Population-Based Analysis of Thoughtful Selection. J Surg Oncol. 2025 Mar;131(3):443-449. doi: 10.1002/jso.27944. Epub 2024 Oct 28.

  PMID: 39466980 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Ajay Goel, PhD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ajay Goel, PhD

CONTACT

626-218-3452; AJGOEL@COH.ORG

Study Design

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

Study Record Dates

• First Submitted: November 3, 2025
• First Posted: November 5, 2025
• Study Start: June 1, 2024
• Primary Completion (Estimated): June 18, 2026
• Study Completion (Estimated): June 18, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)