Liquid Biopsy Using Exosomal miRNA Enables Risk Stratification of Potential Metastasis in Patients With Intrahepatic Cholangiocarcinoma. (EXOMIC)

March 11, 2026 updated by: City of Hope Medical Center

Machine Learning-based Exosome Liquid Biopsy Enables Stratification of Occult Metastasis Risk in Patients With Intrahepatic Cholangiocarcinoma

Occult metastasis at the time of surgery is a major driver of poor outcomes in intrahepatic cholangiocarcinoma (ICC), yet reliable preoperative biomarkers to identify such patients are lacking. The EXOMIC study aims to develop and validate a circulating exosomal microRNA (exo-miRNA)-based liquid biopsy assay to detect occult metastasis preoperatively in patients with resectable ICC.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Intrahepatic cholangiocarcinoma (ICC) incidence is rising globally, and prognosis remains poor. Patients harboring occult micrometastases that are not detected on preoperative imaging often experience rapid recurrence and significantly worse survival. Tumor-derived exosomes contribute to pre-metastatic niche formation and carry microRNAs that reflect aggressive metastatic potential. Circulating exosomal microRNA profiles may serve as non-invasive biomarkers to reveal occult metastasis before surgery.

Preoperative exosomes will be analyzed using small RNA sequencing (discovery) followed by RT-qPCR validation and machine-learning modeling to develop a predictive score for occult metastasis. The study will evaluate diagnostic performance (sensitivity, specificity, accuracy, AUROC), prognostic relevance (OS/RFS), and clinical utility (decision curve analysis) to establish a biologically informed framework for treatment stratification in ICC.

Study Type

Observational

Enrollment (Actual)

230

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91016
        • City of Hope Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

250

Description

Inclusion Criteria:

  • Histologically confirmed ICC (clinical stage I-III).
  • Undergoing curative-intent hepatectomy.
  • Availability of preoperative pasma or serum sample (≥200 µL).
  • Standard staging imaging completed per institutional protocol.
  • Written informed consent.

Exclusion Criteria:

  • Extrahepatic cholangiocarcinoma or gallbladder cancer.
  • Synchronous non-ICC malignancy.
  • Inadequate clinical follow-up.
  • Inability to consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Training Cohort - ICC with Occult Metastasis

The cohort of ICC patients who had occult metastasis detected at the time of surgery.

Preoperative samples were analyzed using the EXOMIC qRT-PCR assay to validate candidate exosomal microRNAs identified in the discovery cohort.
Diagnostic test: EXOMIC assay (qRT-PCR validation)

Quantitative reverse transcription PCR (qRT-PCR)-based validation of candidate exosomal microRNAs identified through small RNA sequencing.

This assay was performed on preoperative serum or plasma samples from independent ICC patient cohorts to validate the predictive value of selected miRNAs for occult metastasis detection prior to surgical resection.
Training Cohort - ICC without Occult Metastasis
The cohort of ICC patients without occult metastasis at the time of surgery. Preoperative samples were analyzed with the EXOMIC qRT-PCR assay to evaluate differential miRNA expression and refine the predictive model for occult metastasis detection.
Diagnostic test: EXOMIC assay (qRT-PCR validation)

Quantitative reverse transcription PCR (qRT-PCR)-based validation of candidate exosomal microRNAs identified through small RNA sequencing.

This assay was performed on preoperative serum or plasma samples from independent ICC patient cohorts to validate the predictive value of selected miRNAs for occult metastasis detection prior to surgical resection.
Validation Cohort - ICC with Occult Metastasis

The cohort of ICC patients with occult metastasis at the time of primary tumor resection.

The EXOMIC qRT-PCR assay was applied to confirm the predictive value of the exosomal miRNA panel in identifying occult metastasis prior to surgery.
Diagnostic test: EXOMIC assay (qRT-PCR validation)

Quantitative reverse transcription PCR (qRT-PCR)-based validation of candidate exosomal microRNAs identified through small RNA sequencing.

This assay was performed on preoperative serum or plasma samples from independent ICC patient cohorts to validate the predictive value of selected miRNAs for occult metastasis detection prior to surgical resection.
Validation Cohort - ICC without Occult Metastasis
The cohort of ICC patients without occult metastasis at the time of surgery. Preoperative samples were analyzed with the EXOMIC qRT-PCR assay to evaluate differential miRNA expression and refine the predictive model for occult metastasis detection.
Diagnostic test: EXOMIC assay (qRT-PCR validation)

Quantitative reverse transcription PCR (qRT-PCR)-based validation of candidate exosomal microRNAs identified through small RNA sequencing.

This assay was performed on preoperative serum or plasma samples from independent ICC patient cohorts to validate the predictive value of selected miRNAs for occult metastasis detection prior to surgical resection.
Discovery Cohort - ICC with Occult Metastasis

Patients with intrahepatic cholangiocarcinoma (ICC) who were found to have occult metastasis at the time of primary tumor resection in the discovery cohort.

Preoperative samples were analyzed using small RNA sequencing to identify exosome-derived microRNAs associated with the presence of occult metastasis.
Diagnostic test: EXOMIC small RNA sequencing

High-throughput small RNA sequencing performed on preoperative serum or plasma samples from patients with intrahepatic cholangiocarcinoma (ICC) to identify exosome-derived microRNAs associated with occult metastasis at the time of surgery.

Sequencing data were analyzed to detect differentially expressed miRNAs between patients with and without occult metastasis in the discovery cohort.
Discovery Cohort - ICC without Occult Metastasis

Patients with ICC who had no occult metastasis at the time of primary tumor resection in the discovery cohort.

Preoperative samples from these patients were analyzed by small RNA sequencing and compared with those from patients with occult metastasis to identify candidate microRNAs.
Diagnostic test: EXOMIC small RNA sequencing

High-throughput small RNA sequencing performed on preoperative serum or plasma samples from patients with intrahepatic cholangiocarcinoma (ICC) to identify exosome-derived microRNAs associated with occult metastasis at the time of surgery.

Sequencing data were analyzed to detect differentially expressed miRNAs between patients with and without occult metastasis in the discovery cohort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence Free Survival
Time Frame: 3 years
The time period from surgery to recurrence of ICC.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 5 years
Time from surgery to death from any cause
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Investigators

  • Principal Investigator: Ajay Goel, PhD, City of Hope Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 21, 2024

Primary Completion (Actual)

January 18, 2026

Study Completion (Actual)

February 18, 2026

Study Registration Dates

First Submitted

November 3, 2025

First Submitted That Met QC Criteria

November 3, 2025

First Posted (Actual)

November 5, 2025

Study Record Updates

Last Update Posted (Actual)

March 13, 2026

Last Update Submitted That Met QC Criteria

March 11, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23228/EXOMIC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data collected for the study will be made available to others, including de-identified participant data, at publication, via a signed data access agreement and at the discretion of the investigators' approval of the proposed use of such data.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Intrahepatic Cholangiocarcinoma (Icc)

Clinical Trials on EXOMIC assay (qRT-PCR validation)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Burkina Faso

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe