Biliary Tract CancerNCT07142226
Role of ctDNA in Genetic Profiling & Outcomes for Advanced BTC
An observational study of Biliary Tract Cancer, run by CHA University at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Biliary Tract Cancer
- What is being tested?
- Circulating Tumor DNA (ctDNA) Testing (ctDNA-based Next-Generation Sequencing (NGS))
- How many people
- 200 participants
- Where
- 1 siteSouth Korea
- Study dates
- 1 Sep 2025to 31 Jan 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
Bundang CHA Medical Center
Seongnam-si, Gyeonggi-do, 13496
Hong Jae Chon, MD. PhD, 82-31-780-3928, minidoctor@cha.ac.kr
About this study
Official title: Role of Circulating Tumor DNA (ctDNA) in Genetic Profiling and Clinical Outcomes for Advanced Biliary Tract Cancer (BTC) Patients - A Multicenter, Prospective, Observational Epidemiology Study
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.
Read the detailed description
Biliary tract cancer (BTC) encompasses a rare and diverse group of tumors characterized by varying anatomical locations-including extrahepatic, intrahepatic, and gallbladder lesions. Therapeutic innovations in advanced BTC are hindered by the rarity and heterogeneity of its subtypes, with particularly high incidence and mortality rates observed in Korea.
Recent advances in molecular profiling have enabled the identification of potential therapeutic targets for BTC. These findings have led to the approval of several therapies for BTC, including those targeting IDH1 mutations, FGFR2 fusions, ERBB2 amplifications, as well as immunotherapies for DNA mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) subtypes. Genomic profiling is essential to detect these targetable alterations, helping to guide appropriate, targeted therapies for patients with BTC. Traditional genomic profiling is typically conducted using formalin-fixed paraffin-embedded (FFPE) tumor tissues; therefore, the challenge of obtaining adequate tumor tissue samples in BTC can impede molecular evaluations. Circulating tumor DNA (ctDNA) from blood may offer an alternative to tissue-based analysis.
In a previous study, the investigators assessed the concordance between ctDNA and tissue genomic profiling in a large cohort of Asian patients with advanced BTC and evaluated the feasibility of liquid biopsy in the treatment of BTC. As a result, ctDNA-based genotyping exhibited acceptable concordance with tissue genomic profiling for clinically significant mutations classified as tier 1 or 2, with a sensitivity of 84.8% and a positive predictive value (PPV) of 79.4%. Notably, high concordance of actionable alterations between ctDNA and tissue for IDH1 mutations was observed, with 100% sensitivity (5/5) and 71.4% PPV (5/7), and for FGFR2 fusions with 66.7% sensitivity (2/3) and 100% PPV (2/2). Additionally, using ctDNA, five IDH1 mutations were identified in tissue samples and two additional IDH1 mutations were detected only in ctDNA.
The IDH1 mutations have significant clinical implications for patients with BTC due to their considerable frequency (approximately 13% in intrahepatic cholangiocarcinoma; range, 9-20%) and the availability of targeted therapy; ivosidenib was approved by both the U.S. Food and Drug Administration (FDA) and the Ministry of Food and Drug Safety (MFDS) in Korea. Although relatively high concordance between ctDNA and tumor tissue for IDH1 mutations was found, the occurrence of these alterations was low, and a more comprehensive comparative analysis is warranted. Therefore, the validation of ctDNA genomic profiling in a larger cohort of patients with BTC is not just a suggestion, but a pressing need to establish its potential as a promising approach for guiding personalized treatment strategies.
Justification for ctDNA in BTC:
The Korean Cancer Study Group (KCSG) Biliary Tract Cancer Subcommittee includes nearly 100 specialists from hospitals across the country. However, not all hospitals in Korea have in-house capabilities for NGS (Next-Generation Sequencing), making it challenging to implement NGS as recommended in biliary tract cancer treatment guidelines. In contrast, ctDNA allows for the detection of a patient's genetic alterations through a simple, non-invasive blood sampling process. This method can identify targetable alterations, facilitating appropriate treatments. Additionally, ctDNA offers a shorter turnaround time, which can help shorten diagnostic timelines and streamline patient access to treatments like ivosidenib.
Long-Term Benefits:
As demonstrated in a recently published study by Immune \& Biotech Diagnostics (IMBDx, Seoul, South Korea), IMBDx's ctDNA test, Alpha Liquid 100, not only identified all five cases of IDH1 mutation detected by conventional tissue NGS but also identified two additional IDH1 mutations that tissue NGS failed to detect. This capability could enable more patients to access treatment with ivosidenib. Moreover, if ctDNA-based NGS testing becomes routine within the KCSG Biliary Tract Cancer Subcommittee, which includes a substantial number of specialists dedicated to treating biliary tract cancer in Korea, it is likely that the use of ctDNA for IDH1 mutation detection will continue beyond this study.
- Conditions
- Biliary Tract Cancer
- Being tested
- Circulating Tumor DNA (ctDNA) Testing (ctDNA-based Next-Generation Sequencing (NGS))
- Keywords
- Biliary Tract Cancer, Biomarker, IDH1 mutation, FGFR2 fusion, Biomarker Analysis, Circulating Tumor DNA (ctDNA)
- Medical subject headings
- Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Circulating Tumor DNA (ctDNA) Testing (ctDNA-based Next-Generation Sequencing (NGS))Genetic
Also called Liquid Biopsy, Alpha Liquid 100
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Genetic: Circulating Tumor DNA (ctDNA) Testing (ctDNA-based Next-Generation Sequencing (NGS)) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Within 4 weeks of study enrollment, prior to initiation of systemic therapy
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: From baseline through study completion, up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2025
- Study start1 Sep 2025
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Biliary Tract CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CHA University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hong Jae Chon, CHA University
- Investigators
- Hong Jae Chon, MD. PhD, Principal investigator, Principal Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07142226
- Sponsor's protocol ID
- CHAMC2025-03-043
- Status last verified
- Mar 2026
- First submitted
- 18 Aug 2025
- Last updated
- 18 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Baria K, De Toni EN, Yu B, Jiang Z, Kabadi SM, Malvezzi M. Worldwide Incidence and Mortality of Biliary Tract Cancer. Gastro Hep Adv. 2022 Apr 15;1(4):618-626. doi: 10.1016/j.gastha.2022.04.007. eCollection 2022.
PubMed 39132071Valle 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.
PubMed 28818953Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DV, Borad MJ, Bridgewater J, Harris WP, Murphy AG, Oh DY, Whisenant J, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Fan B, Wu B, Chamberlain CX, Jiang L, Gliser C, Pandya SS, Valle JW, Zhu AX. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Jun;21(6):796-807. doi: 10.1016/S1470-2045(20)30157-1. Epub 2020 May 13.
PubMed 32416072Zhu AX, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DVT, Borad MJ, Bridgewater JA, Harris WP, Murphy AG, Oh DY, Whisenant JR, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Chamberlain CX, Aguado-Fraile E, Choe S, Wu B, Liu H, Gliser C, Pandya SS, Valle JW, Abou-Alfa GK. Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation: The Phase 3 Randomized Clinical ClarIDHy Trial. JAMA Oncol. 2021 Nov 1;7(11):1669-1677. doi: 10.1001/jamaoncol.2021.3836.
PubMed 34554208Abou-Alfa GK, Sahai V, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R, Paulson AS, Borad MJ, Gallinson D, Murphy AG, Oh DY, Dotan E, Catenacci DV, Van Cutsem E, Ji T, Lihou CF, Zhen H, Feliz L, Vogel A. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020 May;21(5):671-684. doi: 10.1016/S1470-2045(20)30109-1. Epub 2020 Mar 20.
PubMed 32203698Javle M, Roychowdhury S, Kelley RK, Sadeghi S, Macarulla T, Weiss KH, Waldschmidt DT, Goyal L, Borbath I, El-Khoueiry A, Borad MJ, Yong WP, Philip PA, Bitzer M, Tanasanvimon S, Li A, Pande A, Soifer HS, Shepherd SP, Moran S, Zhu AX, Bekaii-Saab TS, Abou-Alfa GK. Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study. Lancet Gastroenterol Hepatol. 2021 Oct;6(10):803-815. doi: 10.1016/S2468-1253(21)00196-5. Epub 2021 Aug 3.
PubMed 34358484Javle M, Borad MJ, Azad NS, Kurzrock R, Abou-Alfa GK, George B, Hainsworth J, Meric-Bernstam F, Swanton C, Sweeney CJ, Friedman CF, Bose R, Spigel DR, Wang Y, Levy J, Schulze K, Cuchelkar V, Patel A, Burris H. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2021 Sep;22(9):1290-1300. doi: 10.1016/S1470-2045(21)00336-3. Epub 2021 Jul 30.
PubMed 34339623Le DT, Kim TW, Van Cutsem E, Geva R, Jager D, Hara H, Burge M, O'Neil B, Kavan P, Yoshino T, Guimbaud R, Taniguchi H, Elez E, Al-Batran SE, Boland PM, Crocenzi T, Atreya CE, Cui Y, Dai T, Marinello P, Diaz LA Jr, Andre T. Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: KEYNOTE-164. J Clin Oncol. 2020 Jan 1;38(1):11-19. doi: 10.1200/JCO.19.02107. Epub 2019 Nov 14.
PubMed 31725351Lamarca A, Kapacee Z, Breeze M, Bell C, Belcher D, Staiger H, Taylor C, McNamara MG, Hubner RA, Valle JW. Molecular Profiling in Daily Clinical Practice: Practicalities in Advanced Cholangiocarcinoma and Other Biliary Tract Cancers. J Clin Med. 2020 Sep 3;9(9):2854. doi: 10.3390/jcm9092854.
PubMed 32899345Strickler JH, Loree JM, Ahronian LG, Parikh AR, Niedzwiecki D, Pereira AAL, McKinney M, Korn WM, Atreya CE, Banks KC, Nagy RJ, Meric-Bernstam F, Lanman RB, Talasaz A, Tsigelny IF, Corcoran RB, Kopetz S. Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer. Cancer Discov. 2018 Feb;8(2):164-173. doi: 10.1158/2159-8290.CD-17-1009. Epub 2017 Dec 1.
PubMed 29196463Goyal L, Saha SK, Liu LY, Siravegna G, Leshchiner I, Ahronian LG, Lennerz JK, Vu P, Deshpande V, Kambadakone A, Mussolin B, Reyes S, Henderson L, Sun JE, Van Seventer EE, Gurski JM Jr, Baltschukat S, Schacher-Engstler B, Barys L, Stamm C, Furet P, Ryan DP, Stone JR, Iafrate AJ, Getz G, Porta DG, Tiedt R, Bardelli A, Juric D, Corcoran RB, Bardeesy N, Zhu AX. Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive Cholangiocarcinoma. Cancer Discov. 2017 Mar;7(3):252-263. doi: 10.1158/2159-8290.CD-16-1000. Epub 2016 Dec 29.
PubMed 28034880Miller AM, Shah RH, Pentsova EI, Pourmaleki M, Briggs S, Distefano N, Zheng Y, Skakodub A, Mehta SA, Campos C, Hsieh WY, Selcuklu SD, Ling L, Meng F, Jing X, Samoila A, Bale TA, Tsui DWY, Grommes C, Viale A, Souweidane MM, Tabar V, Brennan CW, Reiner AS, Rosenblum M, Panageas KS, DeAngelis LM, Young RJ, Berger MF, Mellinghoff IK. Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid. Nature. 2019 Jan;565(7741):654-658. doi: 10.1038/s41586-019-0882-3. Epub 2019 Jan 23.
PubMed 30675060Hwang S, Woo S, Kang B, Kang H, Kim JS, Lee SH, Kwon CI, Kyung DS, Kim HP, Kim G, Kim C, Chon HJ. Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer. J Hepatol. 2025 Apr;82(4):649-657. doi: 10.1016/j.jhep.2024.10.020. Epub 2024 Oct 21.
PubMed 39442892Boscoe AN, Rolland C, Kelley RK. Frequency and prognostic significance of isocitrate dehydrogenase 1 mutations in cholangiocarcinoma: a systematic literature review. J Gastrointest Oncol. 2019 Aug;10(4):751-765. doi: 10.21037/jgo.2019.03.10.
PubMed 31392056
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Circulating Tumor DNA (ctDNA) in Genetic Profiling and Clinical Outcomes for Advanced Biliary Tract Cancer (BTC) Patients - A Multicenter, Prospective, Observational Epidemiology Study
- ClinicalTrials.gov ID
- NCT07142226
- Acronym / sponsor ID
- CHAMC2025-03-043
- Conditions
- Biliary Tract Cancer
- Keywords
- Biliary Tract Cancer, Biomarker, IDH1 mutation, FGFR2 fusion, Biomarker Analysis, Circulating Tumor DNA (ctDNA)
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- CHA UniversityUniversity, hospital or other
- Study start
- 1 Sep 2025 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Jan 2027 (estimated)
- First posted
- 26 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Biliary tract cancer (BTC) encompasses a rare and diverse group of tumors characterized by varying anatomical locations-including extrahepatic, intrahepatic, and gallbladder lesions. Therapeutic innovations in advanced BTC are hindered by the rarity and heterogeneity of its subtypes, with particularly high incidence and mortality rates observed in Korea.
Recent advances in molecular profiling have enabled the identification of potential therapeutic targets for BTC. These findings have led to the approval of several therapies for BTC, including those targeting IDH1 mutations, FGFR2 fusions, ERBB2 amplifications, as well as immunotherapies for DNA mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) subtypes. Genomic profiling is essential to detect these targetable alterations, helping to guide appropriate, targeted therapies for patients with BTC. Traditional genomic profiling is typically conducted using formalin-fixed paraffin-embedded (FFPE) tumor tissues; therefore, the challenge of obtaining adequate tumor tissue samples in BTC can impede molecular evaluations. Circulating tumor DNA (ctDNA) from blood may offer an alternative to tissue-based analysis.
In a previous study, the investigators assessed the concordance between ctDNA and tissue genomic profiling in a large cohort of Asian patients with advanced BTC and evaluated the feasibility of liquid biopsy in the treatment of BTC. As a result, ctDNA-based genotyping exhibited acceptable concordance with tissue genomic profiling for clinically significant mutations classified as tier 1 or 2, with a sensitivity of 84.8% and a positive predictive value (PPV) of 79.4%. Notably, high concordance of actionable alterations between ctDNA and tissue for IDH1 mutations was observed, with 100% sensitivity (5/5) and 71.4% PPV (5/7), and for FGFR2 fusions with 66.7% sensitivity (2/3) and 100% PPV (2/2). Additionally, using ctDNA, five IDH1 mutations were identified in tissue samples and two additional IDH1 mutations were detected only in ctDNA.
The IDH1 mutations have significant clinical implications for patients with BTC due to their considerable frequency (approximately 13% in intrahepatic cholangiocarcinoma; range, 9-20%) and the availability of targeted therapy; ivosidenib was approved by both the U.S. Food and Drug Administration (FDA) and the Ministry of Food and Drug Safety (MFDS) in Korea. Although relatively high concordance between ctDNA and tumor tissue for IDH1 mutations was found, the occurrence of these alterations was low, and a more comprehensive comparative analysis is warranted. Therefore, the validation of ctDNA genomic profiling in a larger cohort of patients with BTC is not just a suggestion, but a pressing need to establish its potential as a promising approach for guiding personalized treatment strategies.
Justification for ctDNA in BTC:
The Korean Cancer Study Group (KCSG) Biliary Tract Cancer Subcommittee includes nearly 100 specialists from hospitals across the country. However, not all hospitals in Korea have in-house capabilities for NGS (Next-Generation Sequencing), making it challenging to implement NGS as recommended in biliary tract cancer treatment guidelines. In contrast, ctDNA allows for the detection of a patient's genetic alterations through a simple, non-invasive blood sampling process. This method can identify targetable alterations, facilitating appropriate treatments. Additionally, ctDNA offers a shorter turnaround time, which can help shorten diagnostic timelines and streamline patient access to treatments like ivosidenib.
Long-Term Benefits:
As demonstrated in a recently published study by Immune \& Biotech Diagnostics (IMBDx, Seoul, South Korea), IMBDx's ctDNA test, Alpha Liquid 100, not only identified all five cases of IDH1 mutation detected by conventional tissue NGS but also identified two additional IDH1 mutations that tissue NGS failed to detect. This capability could enable more patients to access treatment with ivosidenib. Moreover, if ctDNA-based NGS testing becomes routine within the KCSG Biliary Tract Cancer Subcommittee, which includes a substantial number of specialists dedicated to treating biliary tract cancer in Korea, it is likely that the use of ctDNA for IDH1 mutation detection will continue beyond this study.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group 1: Advanced BTC Patients | – | Genetic: Circulating Tumor DNA (ctDNA) Testing (ctDNA-based Next-Generation Sequencing (NGS))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 |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- 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:
- Age ≥ 19 years at the time of enrollment.
- Willingness to provide a blood sample for ctDNA analysis.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Circulating Tumor DNA (ctDNA) Testing (ctDNA-based Next-Generation Sequencing (NGS))Also: Liquid Biopsy, Alpha Liquid 100Peripheral 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. | Genetic | Group 1: Advanced BTC Patients |
Primary outcome
Concordance Between ctDNA and Tissue-Based Genomic Profiling
Time frame: Within 4 weeks of study enrollment, prior to initiation of systemic therapy
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.
3 secondary outcomes
Detection Rate of Actionable Alterations using ctDNA
Time frame: At baseline (prior to treatment initiation, within 4 weeks of enrollment)
Positive Predictive Value (PPV) and Sensitivity of ctDNA
Time frame: At baseline (prior to treatment initiation, within 4 weeks of enrollment)
Feasibility of ctDNA Testing in Clinical Practice
Time frame: From baseline through study completion, up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2026.
- Background: PubMed 39132071Baria K, De Toni EN, Yu B, Jiang Z, Kabadi SM, Malvezzi M. Worldwide Incidence and Mortality of Biliary Tract Cancer. Gastro Hep Adv. 2022 Apr 15;1(4):618-626. doi: 10.1016/j.gastha.2022.04.007. eCollection 2022.
- Background: PubMed 28818953Valle 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.
- Background: PubMed 32416072Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DV, Borad MJ, Bridgewater J, Harris WP, Murphy AG, Oh DY, Whisenant J, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Fan B, Wu B, Chamberlain CX, Jiang L, Gliser C, Pandya SS, Valle JW, Zhu AX. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Jun;21(6):796-807. doi: 10.1016/S1470-2045(20)30157-1. Epub 2020 May 13.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hong Jae Chon, MD. PhD principal investigator
Principal Investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Biliary Tract Cancer, run by CHA University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hong Jae Chon, MD. PhD (82-31-780-3928, minidoctor@cha.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concordance Between ctDNA and Tissue-Based Genomic Profiling (time frame: Within 4 weeks of study enrollment, prior to initiation of systemic therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07142226, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2026.