Trials / Recruiting

RecruitingNCT07176962

A Cell-free DNA Methylation Blood-Based Test for Biliary Tract Cancers Screening

A Cell-free DNA Methylation Liquid Biopsy for Diagnosis and Management of Biliary Tract Cancers

Status: Recruiting
Phase: —
Study type: Observational
Enrollment: 1,800 (estimated)

Sponsor: Yingbin Liu, MD, PhD, FACS · Academic / Other
Sex: All
Age: 18 Years – 80 Years
Healthy volunteers: Accepted

Summary

Biliary tract carcinoma (BTC), including gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma, ranks sixth in incidence among gastrointestinal malignancies and tenth in cancer-related mortality worldwide. Due to the lack of specific early symptoms, high malignancy, and frequent recurrence and metastasis, the rate of curative resection is only about 16.5%, and the overall 5-year survival rate is less than 5%. Early and accurate detection is therefore critical for improving patient outcomes. Circulating tumor DNA (ctDNA), a fraction of circulating free DNA (cfDNA), carries genetic and epigenetic information from tumor cells and can be detected even at the early stages of cancer development. Among various liquid biopsy biomarkers, ctDNA methylation shows particular advantages in sensitivity and specificity for early cancer detection and monitoring. This study aims to evaluate the application of cfDNA methylation liquid biopsy in the diagnosis and management of BTC.

Detailed description

Biliary tract carcinoma (BTC), encompassing gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma, is an aggressive malignancy with poor prognosis. Globally, it ranks sixth in incidence among gastrointestinal cancers and tenth in cancer-related mortality. BTC is characterized by the absence of specific early symptoms, high degree of malignancy, and a strong tendency for recurrence and metastasis. The curative resection rate remains around 16.5%, and the overall 5-year survival rate is less than 5%. Biliary tract inflammation (such as cholangitis, acute cholecystitis, sclerosing cholangitis, and autoimmune cholangitis) can lead to abnormal CA19-9 elevation. In addition, IgG4-related sclerosing cholangitis often affects elderly patients and may mimic hilar cholangiocarcinoma, creating diagnostic challenges. Imaging alone often lacks accuracy in differentiating benign from malignant biliary lesions, resulting in misdiagnosis and inappropriate clinical decision-making. The number of patients with incidentally detected BTC during surgery is rapidly increasing, and reoperations impose substantial trauma and socioeconomic burden. Circulating tumor DNA (ctDNA) refers to DNA fragments released into the bloodstream from tumor cells through apoptosis, necrosis, or secretion. ctDNA carries genomic alterations (point mutations, indels, CNVs, fusions), epigenetic modifications (DNA methylation \[5mC\], hydroxymethylation \[5hmC\]), and structural features (fragment length, fragmentation patterns). Circulating free DNA (cfDNA) represents the total extracellular DNA in plasma or serum, of which ctDNA accounts for less than 1%. Accumulating evidence shows that ctDNA is detectable in the early stages of tumorigenesis, highlighting its clinical potential in early detection, diagnosis, treatment guidance, and post-treatment monitoring. The choice of biomarker type is key to liquid biopsy applications, and ctDNA methylation offers distinct advantages. Liquid biopsy analytes include circulating tumor cells (CTCs), ctDNA, exosomes, and microRNAs (miRNAs), each with unique detection characteristics. ctDNA, directly derived from tumor cells, provides relatively high sensitivity for early detection and is currently the most widely used target in clinical practice. Research on ctDNA has focused mainly on methylation, somatic mutations, and copy number variations. Among these, ctDNA methylation balances both signal abundance and signal strength, offering clear advantages over other approaches. Methylation analysis methods include restriction enzyme digestion, affinity enrichment, and bisulfite conversion. Among them, bisulfite-based approaches are the most established and widely used. Therefore, the application of cfDNA methylation liquid biopsy in BTC for early screening, differential diagnosis, prognostic monitoring, and therapeutic guidance holds great significance for improving diagnosis, treatment, and patient outcomes.

Conditions

Timeline

Start date: 2020-01-01
Primary completion: 2026-03-21
Completion: 2026-05-01
First posted: 2025-09-16
Last updated: 2025-09-16

Locations

1 site across 1 country: China

Source: ClinicalTrials.gov record NCT07176962. Inclusion in this directory is not an endorsement.