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

ConditionBiliary Tract Cancer (BTC)

Trial statusNot yet recruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age19+

SponsorCHA University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial 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.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Bile Sampling for ctDNA Analysis
Other intervention
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.

Treatment groups

100 Participants

are divided into 1 treatment group

Group A: Advanced Biliary Tract Cancer Patients1 intervention

Trial outcomes

Primary outcomes

Concordance rate of genetic variants between bile ctDNA and tumor tissue DNA

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.

Time frame

Baseline

Secondary outcomes

Frequency of actionable genomic alterations detected in bile ctDNA

Frequency of FGFR2 fusion, IDH1 mutation, and HER2 amplification detected by NGS-based analysis of bile-derived ctDNA.

Time frame

Up to 24 months

Concordance rate of genetic variants between bile ctDNA and plasma ctDNA

Concordance of genetic variants detected by NGS between bile ctDNA and plasma ctDNA, assessed using sensitivity and positive predictive value where applicable.

Time frame

Up to 24 months

Mutation detection rate comparison among bile ctDNA, plasma ctDNA, and tumor tissue DNA

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

Time frame

Up to 24 months

Other outcomes

Association between bile ctDNA maximum variant allele frequency (max VAF) and clinical outcomes

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.

Time frame

Up to 24 months

Characteristics of genetic variants uniquely detected in bile ctDNA

Description of genetic variants detected in bile ctDNA but not identified in tumor tissue NGS.

Time frame

Up to 24 months

Identification of potential therapeutic targets through bile ctDNA-based genomic analysis

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

Time frame

Up to 24 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

CHA University

Lead sponsor

Source ClinicalTrials.gov

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