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

NCT ID: NCT07224737

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

250 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-06-21

Study Completion Date

2026-06-18

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Intrahepatic Cholangiocarcinoma (Icc)

Keywords

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Exosomal miRNA ICC Liquid Biopsy Occult metastasis Tumor recurrence Liver cancer

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Study Groups

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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.

EXOMIC assay (qRT-PCR validation)

Intervention Type DIAGNOSTIC_TEST

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.

EXOMIC assay (qRT-PCR validation)

Intervention Type DIAGNOSTIC_TEST

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.

EXOMIC assay (qRT-PCR validation)

Intervention Type DIAGNOSTIC_TEST

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.

EXOMIC small RNA sequencing

Intervention Type DIAGNOSTIC_TEST

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.

EXOMIC small RNA sequencing

Intervention Type DIAGNOSTIC_TEST

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.

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.

EXOMIC assay (qRT-PCR validation)

Intervention Type DIAGNOSTIC_TEST

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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City of Hope Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ajay Goel, PhD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

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City of Hope Medical Center

Duarte, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Ajay Goel, PhD

Role: CONTACT

Phone: 626-218-3452

Email: [email protected]

Facility Contacts

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Ajay Goel, PhD

Role: primary

References

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Reference Type BACKGROUND
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Other Identifiers

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23228/EXOMIC

Identifier Type: -

Identifier Source: org_study_id