Role of ctDNA in Genetic Profiling & Outcomes for Advanced BTC

NCT07142226 | Recruiting

• 1 other identifier: CHAMC2025-03-043
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Biliary Tract Cancer

Keywords

Biliary Tract Cancer; Biomarker; IDH1 mutation; FGFR2 fusion; Biomarker Analysis; Circulating Tumor DNA (ctDNA)

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (3)

• Detection Rate of Actionable Alterations using ctDNA

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

• Positive Predictive Value (PPV) and Sensitivity of ctDNA

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

• Feasibility of ctDNA Testing in Clinical Practice

  From baseline through study completion, up to 24 months

Other Outcomes (3)

• Correlation between Genetic Alterations and Clinical Outcomes

  From baseline through follow-up, up to 36 months

• Identification of ctDNA-only Mutations

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

• Implementation within KCSG Biliary Tract Cancer Network

  From baseline through study completion, up to 24 months

Study Arms (1)

Group 1: Advanced BTC Patients

Description: Patients with histologically or cytologically confirmed advanced biliary tract cancer (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer) who are enrolled prospectively across participating centers in Korea. Number of Participants: 200 (anticipated) Cohort Type: Single observational cohort

Genetic: Circulating Tumor DNA (ctDNA) Testing (ctDNA-based Next-Generation Sequencing (NGS))

Interventions

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.

Also known as: Liquid Biopsy, Alpha Liquid 100

Group 1: Advanced BTC Patients

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study 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.

You may qualify if:

• Patients with histologically confirmed advanced or metastatic biliary tract cancer (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer).
• Patients who meet one of the following conditions:
• 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.
• Willingness to provide a blood sample for ctDNA analysis.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CHA University: lead

Study Sites (1)

Bundang CHA Medical Center

Seongnam-si, Gyeonggi-do, 13496, South Korea

RECRUITING

Related Publications (14)

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  PMID: 39132071 BACKGROUND

• Valle JW, Lamarca A, Goyal L, Barriuso J, Zhu AX. New Horizons for Precision Medicine in Biliary Tract Cancers. Cancer Discov. 2017 Sep;7(9):943-962. doi: 10.1158/2159-8290.CD-17-0245. Epub 2017 Aug 17.

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  PMID: 32416072 BACKGROUND

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Biospecimen

Retention: SAMPLES WITH DNA

Blood

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Circulating Tumor DNA; Liquid Biopsy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Cell-Free Nucleic Acids; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides; DNA, Neoplasm; DNA; Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Investigative Techniques

Study Officials

• Hong Jae Chon, MD. PhD

  Principal Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hong Jae Chon, MD. PhD

CONTACT

82-31-780-3928; minidoctor@cha.ac.kr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 18, 2025
• First Posted: August 26, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)