Bile ctDNA Genomic Profiling and Concordance With Tumor Tissue in Biliary Tract Cancer

October 7, 2026 updated by: Hong Jae Chon, CHA University

A Prospective Multicenter Observational Study to Evaluate Genomic Profiling of Bile-Derived Circulating Tumor DNA (Bile ctDNA) and Its Concordance With Tumor Tissue DNA in Patients With Advanced Biliary Tract Cancer (BTC)

This study is being done to find out whether bile fluid can be used to detect genetic changes in tumors of patients with advanced biliary tract cancer (BTC), such as cancer of the bile ducts or gallbladder.

Currently, doctors often use a sample of tumor tissue to look for genetic changes that can help guide treatment decisions, including the use of targeted therapies. However, in biliary tract cancer, it can be difficult or risky to collect enough tumor tissue for this kind of testing.

This study will collect a small amount of leftover bile (about 20 mL) during a procedure that patients are already having for medical reasons (such as endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD), which are used to drain bile). A blood sample (about 20 mL) will also be collected at the same time patients are already having blood drawn as part of their regular care. No additional needle sticks or procedures will be done only for this study.

Researchers will analyze the genetic material found in the bile and blood samples and compare the results with the genetic testing already done on the patient's tumor tissue. The main goal is to see how closely the genetic changes found in bile match those found in tumor tissue. The study will also look at whether bile testing can detect genetic changes that may help guide treatment, and whether these results are related to how patients respond to treatment and their long-term outcomes.

About 100 patients with advanced biliary tract cancer will take part in this study at 4 hospitals in South Korea.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Biliary tract cancer (BTC) is a heterogeneous and aggressive malignancy with poor prognosis, especially in advanced or metastatic stages where surgical resection is not feasible. The current standard first-line therapy with gemcitabine and cisplatin, now combined with immune checkpoint inhibitors, still provides limited long-term survival. Targeted therapies - including FGFR inhibitors for FGFR2 fusions, IDH1 inhibitors, and HER2-directed agents - have improved outcomes in molecularly selected subsets of patients. However, tumor tissue acquisition remains challenging in BTC due to the anatomically inaccessible location of many tumors and frequently insufficient tumor content, limiting the ability to perform comprehensive genomic profiling in a substantial proportion of patients.

Circulating tumor DNA (ctDNA) has emerged as a promising, minimally invasive biomarker for molecular profiling in BTC. While plasma-based ctDNA has shown acceptable concordance with tissue-based next-generation sequencing (NGS) in prior studies, its sensitivity is reduced in patients with locally advanced disease due to lower circulating DNA concentrations. Because bile is in direct contact with biliary tumors, it may harbor tumor-derived DNA at substantially higher concentrations and variant allele frequencies than plasma, suggesting the potential for improved sensitivity and reliability in mutation detection. Preliminary data support higher bile DNA yield and higher concordance with tumor tissue NGS compared with plasma ctDNA, and bile ctDNA alterations have also shown associations with survival outcomes. However, evidence supporting the clinical utility of bile ctDNA remains limited, and no large-scale prospective study has systematically evaluated its concordance with tumor tissue genomic profiling.

This prospective, multicenter, observational study will enroll 100 Korean patients with advanced or metastatic BTC from 4 hospitals, using a competitive enrollment strategy with a target of approximately 50% intrahepatic cholangiocarcinoma. Eligible patients provide a single blood sample (approximately 20 mL) and a single bile sample (approximately 20 mL, collected as residual fluid during clinically indicated biliary drainage via endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD)) prior to first-line systemic anti-cancer therapy; no additional invasive procedure is performed solely for research purposes. Collected samples are sent to an external laboratory for ctDNA extraction and NGS-based genomic analysis.

The primary objective is to evaluate the concordance of genetic variants between bile ctDNA and tumor tissue DNA in patients with advanced BTC. Secondary objectives include:

  • Assessing the frequency of actionable genomic alterations (FGFR2 fusion, IDH1 mutation, HER2 amplification) detected in bile ctDNA
  • Evaluating the concordance of genetic variants between bile ctDNA and plasma ctDNA
  • Comparing mutation detection rates among bile ctDNA, plasma ctDNA, and tumor tissue DNA Exploratory analyses will examine the association between bile ctDNA maximum variant allele frequency (max VAF) and tumor burden/clinical prognosis, characterize additional genetic variants uniquely detected in bile ctDNA, and explore potential therapeutic targets identified through bile ctDNA-based genomic analysis.

This study is expected to provide evidence for the clinical utility of bile ctDNA as a complementary or alternative molecular diagnostic tool in BTC, particularly for patients in whom tumor tissue acquisition is difficult, and to contribute to the development of precision medicine strategies for patient-tailored treatment selection.

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

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

Study Contact

Study Locations

  • South Korea
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, South Korea, 13496
        • CHA Bundang Medical Center
        • Principal Investigator:
          • Hong Jae Chon
        • Contact:

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

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The study population consists of adult patients with advanced (unresectable or metastatic) biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer, who are treated at 4 tertiary hospitals in South Korea. Eligible patients are those who are about to undergo clinically indicated biliary drainage (ERCP or PTBD) prior to first-line systemic anti-cancer therapy, from whom residual bile can be collected without any additional invasive procedure. Patients may be enrolled at the time of bile collection even before histologic confirmation of biliary tract cancer; however, only patients with subsequently confirmed histologic diagnosis are included in the final analysis. Enrollment is conducted on a competitive basis across participating sites, with a target of approximately 50% of enrolled patients having intrahepatic cholangiocarcinoma, given the higher frequency of actionable mutations in this subtype.

Description

Inclusion Criteria:

  • Adult male or female patients aged 19 years or older
  • Histologically confirmed advanced biliary tract cancer (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer), or clinically suspected biliary tract cancer pending histologic confirmation
  • Prior to first-line systemic anti-cancer therapy (patients who relapsed ≥6 months after curative surgery or adjuvant chemotherapy are eligible)
  • Tumor tissue next-generation sequencing (NGS) already performed or planned
  • Willing to provide blood and bile samples for ctDNA analysis

Exclusion Criteria:

  • Patients from whom a bile sample cannot be obtained during clinically indicated biliary drainage (ERCP or PTBD)
  • Patients who decline blood sampling for ctDNA testing
  • Patients unable to provide informed 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

  • Observational Models: COHORT
  • Time Perspectives: PROSPECTIVE

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Advanced Biliary Tract Cancer Patients

Patients with histologically confirmed advanced or metastatic biliary tract cancer (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer). Participants will provide bile samples for circulating tumor DNA (ctDNA) analysis before systemic therapy or prior to subsequent treatment.
Other: Bile Sampling for ctDNA Analysis

Bile (approximately 20 mL) is collected once from patients with advanced biliary tract cancer, prior to first-line systemic therapy. The sample is obtained as residual fluid during a clinically indicated biliary drainage procedure (ERCP or PTBD); no additional invasive procedure is performed for research purposes. The sample is sent to an external laboratory for circulating tumor DNA (ctDNA) extraction and next-generation sequencing (NGS)-based genomic analysis, to evaluate concordance of genetic variants with tumor tissue DNA and, where available, plasma ctDNA.

Other Names:
  • Liquid Biopsy; Bile Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Concordance rate of genetic variants between bile ctDNA and tumor tissue DNA
Time Frame: Baseline

Genetic variants detected by next-generation sequencing (NGS) of bile-derived circulating tumor DNA (ctDNA) will be compared with variants identified by tumor tissue NGS performed as part of standard clinical care. Concordance will be assessed using sensitivity and positive predictive value (PPV), with 90% confidence intervals.
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of actionable genomic alterations detected in bile ctDNA
Time Frame: Up to 24 months

Frequency of FGFR2 fusion, IDH1 mutation, and HER2 amplification detected by NGS-based analysis of bile-derived ctDNA.
Up to 24 months
Concordance rate of genetic variants between bile ctDNA and plasma ctDNA
Time Frame: Up to 24 months

Concordance of genetic variants detected by NGS between bile ctDNA and plasma ctDNA, assessed using sensitivity and positive predictive value where applicable.
Up to 24 months
Mutation detection rate comparison among bile ctDNA, plasma ctDNA, and tumor tissue DNA
Time Frame: Up to 24 months

Proportion of genetic variants detected in each of the three sample types (bile ctDNA, plasma ctDNA, tumor tissue DNA), compared across sample sources.
Up to 24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association between bile ctDNA maximum variant allele frequency (max VAF) and clinical outcomes
Time Frame: Up to 24 months

Association between bile ctDNA max VAF, tumor burden, and progression-free survival (PFS) and overall survival (OS), estimated using Kaplan-Meier curves and Cox proportional hazards regression.
Up to 24 months
Characteristics of genetic variants uniquely detected in bile ctDNA
Time Frame: Up to 24 months

Description of genetic variants detected in bile ctDNA but not identified in tumor tissue NGS.
Up to 24 months
Identification of potential therapeutic targets through bile ctDNA-based genomic analysis
Time Frame: Up to 24 months

Exploratory identification of additional actionable or potentially targetable genomic alterations detected through bile ctDNA analysis.
Up to 24 months

Collaborators and Investigators

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

Sponsor

CHA University

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 (Estimated)

October 1, 2026

Primary Completion (Estimated)

August 31, 2028

Study Completion (Estimated)

August 31, 2028

Study Registration Dates

First Submitted

September 15, 2026

First Submitted That Met QC Criteria

September 15, 2026

First Posted (Actual)

September 21, 2026

Study Record Updates

Last Update Posted (Actual)

October 13, 2026

Last Update Submitted That Met QC Criteria

October 7, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHAMC 2026-06-033

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

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