ctDNA in Genetic Profiling and Clinical Outcomes of Advanced Biliary Tract Cancer

NCT ID: NCT07151118

Last Updated: 2025-09-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-09-01

Study Completion Date

2027-08-31

Brief Summary

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This prospective, multicenter, observational study aims to evaluate the role of circulating tumor DNA (ctDNA) in advanced or metastatic biliary tract cancer (BTC) patients in Korea. Tissue-based genomic profiling is often limited due to the anatomical challenges of tumor biopsy and insufficient DNA quality. ctDNA analysis offers a minimally invasive alternative for identifying actionable genetic alterations, including Fibroblast Growth Factor Receptor 2 (FGFR2) fusions, Isocitrate Dehydrogenase 1 (IDH1) mutations, and Human Epidermal Growth Factor Receptor 2 (HER2) amplifications. The study will recruit 100 patients across 11 institutions and assess the concordance between ctDNA and tissue genomic profiling, as well as the clinical relevance of ctDNA in predicting treatment outcomes and prognosis.

Detailed Description

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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 provides limited survival benefit, with median overall survival around 11-12 months. Targeted therapies, such as FGFR inhibitors for FGFR2 fusions and IDH1 inhibitors, as well as immune checkpoint inhibitors, have improved outcomes in subsets of patients. However, tumor tissue acquisition remains challenging in BTC, limiting the ability to perform comprehensive genomic profiling.

Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for molecular profiling, treatment monitoring, and prognosis assessment. Prior studies demonstrated acceptable concordance between ctDNA-based and tissue-based next-generation sequencing, particularly for FGFR2 fusions, and highlighted the potential of ctDNA in identifying additional genomic alterations not detected in tissue samples.

This prospective study will enroll 100 Korean patients with advanced or metastatic BTC from 11 hospitals. Approximately two-thirds of patients will provide blood samples prior to first-line systemic therapy, while one-third will provide samples before subsequent therapy. Additional blood draws will be performed at progression in patients harboring FGFR2 fusion, IDH1 mutation, or HER2 amplification. Collected samples will be analyzed by a central laboratory (SCL Healthcare, a precision medicine service provider specializing in biomarker-based diagnostics).

The primary objective is to evaluate the frequency of actionable genomic alterations, especially FGFR2 fusions, detected by ctDNA in advanced BTC patients. Secondary objectives include:

* Assessing the concordance between ctDNA and tissue genomic profiling
* Evaluating the proportion of patients who received targeted therapy based on ctDNA results (e.g., pemigatinib \[Pemazyre®\])
* Exploring associations between ctDNA maximum variant allele frequency (max VAF) and survival outcomes
* Identifying potential resistance mechanisms and clonal evolution during targeted therapy

This study is expected to provide robust evidence for the clinical utility of ctDNA in BTC and contribute to the establishment of precision medicine approaches, potentially supporting future guideline development and regulatory approval of ctDNA assays in Korea and globally.

Conditions

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Biliary Tract Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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 blood samples for circulating tumor DNA (ctDNA) analysis before systemic therapy or prior to subsequent treatment.

Blood Sampling for ctDNA Analysis

Intervention Type OTHER

Approximately 20 mL of peripheral blood will be collected from patients with advanced biliary tract cancer. Samples will be obtained prior to systemic therapy initiation (in about two-thirds of patients) or prior to subsequent therapy (in about one-third of patients). Additional blood draws may be performed at progression in patients with FGFR2 fusion, IDH1 mutation, or HER2 amplification. Collected samples will be centrally analyzed for genomic alterations using ctDNA profiling.

Interventions

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Blood Sampling for ctDNA Analysis

Approximately 20 mL of peripheral blood will be collected from patients with advanced biliary tract cancer. Samples will be obtained prior to systemic therapy initiation (in about two-thirds of patients) or prior to subsequent therapy (in about one-third of patients). Additional blood draws may be performed at progression in patients with FGFR2 fusion, IDH1 mutation, or HER2 amplification. Collected samples will be centrally analyzed for genomic alterations using ctDNA profiling.

Intervention Type OTHER

Other Intervention Names

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Liquid Biopsy; Plasma Collection

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed advanced or metastatic biliary tract cancer (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder carcinoma)
* Patients meeting one of the following conditions:

* Prior to initiation of first-line systemic therapy
* Patients who previously received systemic therapy and are able to provide a blood sample prior to initiation of subsequent therapy
* Age ≥ 19 years at the time of enrollment
* Willingness and ability to provide blood samples for ctDNA analysis

Exclusion Criteria

* Refusal to provide blood samples for ctDNA testing
* Inability to provide written informed consent
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Handok Inc.

INDUSTRY

Sponsor Role collaborator

CHA University

OTHER

Sponsor Role lead

Responsible Party

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Hong Jae Chon

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hong Jae Chon

Role: PRINCIPAL_INVESTIGATOR

Principal Investigator

Locations

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CHA Bundang Medical Center

Seongnam-si, Gyeonggi-do, South Korea

Site Status

Countries

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South Korea

Central Contacts

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Hong Jae Chon, MD. PhD

Role: CONTACT

82-31-780-3928

Hong Jae Chon, MD. PhD

Role: CONTACT

82-31-780-3928

References

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Other Identifiers

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CHAMC2025-03-041

Identifier Type: -

Identifier Source: org_study_id

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