Role of ctDNA in Genetic Profiling & Outcomes for Advanced BTC

ConditionBiliary Tract Cancer

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age19+

SponsorCHA University

About this trial

Biliary tract cancer (BTC) is a rare and heterogeneous disease with high incidence and mortality in Korea. Molecular profiling has enabled the identification of actionable alterations such as Isocitrate Dehydrogenase 1 (IDH1) mutations, FGFR2 fusions, ERBB2 amplifications, and dMMR/MSI-H status. However, the utility of tumor tissue-based next-generation sequencing (NGS) is often limited by difficulties in obtaining adequate tissue samples and the lack of in-house sequencing capacity across many hospitals.

Circulating tumor DNA (ctDNA) analysis offers a minimally invasive alternative that can provide rapid and reliable genomic profiling. In a previous study, ctDNA testing showed high concordance with tissue-based genomic profiling for clinically significant alterations, particularly IDH1 mutations, and identified additional mutations not detected in tumor tissue. These findings suggest that ctDNA may expand access to targeted therapies such as ivosidenib .

This multicenter, prospective, observational epidemiology study, organized by the Korean Cancer Study Group (KCSG) Biliary Tract Cancer Subcommittee, will evaluate the clinical utility of ctDNA-based genomic profiling in patients with advanced BTC. The study will assess concordance between ctDNA and tumor tissue sequencing, describe the prevalence of actionable alterations, and explore the impact of ctDNA testing on treatment decisions and clinical outcomes. By leveraging a nationwide network of BTC specialists, this study seeks to validate ctDNA as a feasible and scalable tool for precision oncology, supporting timely and personalized therapy for patients with BTC.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients with histologically confirmed advanced or metastatic biliary tract cancer (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer).

Patients prior to initiation of first-line systemic chemotherapy, or

Patients previously treated with systemic chemotherapy who can provide a blood sample immediately before starting subsequent therapy.

Age ≥ 19 years at the time of enrollment.

Disqualifiers

Patients who refuse to provide blood samples for ctDNA testing.

Patients unable to provide written informed consent.

Patients concurrently enrolled in a similar study within the same institution. Prior screening will be performed to prevent duplicate enrollment.

Trial population

Patients with histologically confirmed advanced or metastatic biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. Eligible patients are either treatment-naïve prior to first-line systemic chemotherapy or previously treated patients able to provide a blood sample before starting subsequent therapy. All participants must be 19 years of age or older and willing to provide blood samples for ctDNA analysis.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Circulating Tumor DNA (ctDNA) Testing (ctDNA-based Next-Generation Sequencing (NGS))
Genetic
Peripheral blood will be collected from patients with advanced biliary tract cancer for circulating tumor DNA (ctDNA) testing. Next-generation sequencing (NGS) will be performed to detect clinically relevant genomic alterations, including IDH1 mutations, FGFR2 fusions, ERBB2 amplifications, and MSI-H/dMMR. The ctDNA results will be compared with tissue-based genomic profiling to evaluate concordance and clinical utility.

Treatment groups

200 Participants

are divided into 1 treatment group

Group A: Group 1: Advanced BTC Patients1 intervention

Trial outcomes

Primary outcomes

Concordance Between ctDNA and Tissue-Based Genomic Profiling

The proportion of concordance between circulating tumor DNA (ctDNA)-based next-generation sequencing (NGS) and tissue-based genomic profiling in detecting clinically relevant genetic alterations (e.g., IDH1 mutations, FGFR2 fusions, ERBB2 amplifications, MSI-H/dMMR) among patients with advanced biliary tract cancer.

Time frame

Within 4 weeks of study enrollment, prior to initiation of systemic therapy

Secondary outcomes

Detection Rate of Actionable Alterations using ctDNA

To determine the detection rate of clinically significant alterations such as IDH1 mutations, FGFR2 fusions, and ERBB2 amplifications by ctDNA analysis.

Time frame

At baseline (prior to treatment initiation, within 4 weeks of enrollment)

Positive Predictive Value (PPV) and Sensitivity of ctDNA

To assess the PPV and sensitivity of ctDNA profiling compared with matched tissue NGS results.

Time frame

At baseline (prior to treatment initiation, within 4 weeks of enrollment)

Feasibility of ctDNA Testing in Clinical Practice

To evaluate the feasibility of ctDNA analysis in a real-world multicenter setting, including sample collection success rate, assay success rate, and turnaround time.

Time frame

From baseline through study completion, up to 24 months

Other outcomes

Correlation between Genetic Alterations and Clinical Outcomes

To explore associations between specific genetic alterations (e.g., IDH1 mutations, FGFR2 fusions) and clinical outcomes such as overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

Time frame

From baseline through follow-up, up to 36 months

Identification of ctDNA-only Mutations

To investigate genetic alterations detected exclusively by ctDNA but not by tissue-based NGS, with a particular focus on IDH1 mutations.

Time frame

At baseline (prior to treatment initiation, within 4 weeks of enrollment)

Implementation within KCSG Biliary Tract Cancer Network

To assess the potential for ctDNA-based genomic testing to be integrated into routine practice across the Korean Cancer Study Group (KCSG) Biliary Tract Cancer Subcommittee network and its implications for future treatment guidelines.

Time frame

From baseline through study completion, 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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