NCT07224815

cfDNA 5mC/5hmC Biomarkers to Predict Chemotherapy Response in Metastatic Colorectal Cancer

Development of a cfDNA 5mC/5hmC-based Epigenetic Biomarker Panel to Predict Chemotherapy Efficacy in Metastatic Colorectal Cancer

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 600 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The EpiCORE study aims to identify cfDNA-based epigenetic markers predictive of response to first-line chemotherapy (FOLFOX or FOLFIRI) in metastatic colorectal cancer (mCRC). By integrating 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiling, this study seeks to establish a non-invasive biomarker panel capable of distinguishing responders from non-responders.

Detailed description

Despite the introduction of multi-agent chemotherapy regimens such as FOLFOX (5-FU, leucovorin, oxaliplatin) and FOLFIRI (5-FU, leucovorin, irinotecan), treatment outcomes in metastatic colorectal cancer (mCRC) remain highly variable. Current predictive biomarkers, such as RAS/BRAF mutation or microsatellite instability, fail to accurately forecast response to cytotoxic chemotherapy. Emerging evidence suggests that cfDNA methylation (5mC) and hydroxymethylation (5hmC) patterns reflect tumor biology and drug sensitivity, offering a promising avenue for precision chemotherapy. The EpiCORE study integrates genome-wide 5mC/5hmC sequencing and targeted validation assays to identify and confirm epigenetic determinants of chemotherapy efficacy. Discovery phase: Genome-wide 5mC/5hmC profiling of cfDNA from patients treated with first-line FOLFOX or FOLFIRI to identify candidate regions associated with treatment response. Training phase: Targeted sequencing and model construction based on candidate loci. Validation phase: qPCR-based testing to confirm predictive accuracy of the finalized EpiCORE panel. This study aims to establish a robust cfDNA biomarker framework for predicting and monitoring chemotherapy response in mCRC, contributing to individualized therapeutic decision-making.

Conditions

• CRC (Colorectal Cancer)

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	cfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase)	Genome-wide profiling of cfDNA methylation and hydroxymethylation from pre-treatment plasma to identify molecular determinants associated with chemotherapy efficacy (PFS ≥ 12M vs \< 12M).
DIAGNOSTIC_TEST	EpiCORE Assay (Targeted Sequencing / qPCR Validation)	Targeted validation of cfDNA 5mC/5hmC markers from discovery phase using sequencing and qPCR to build and validate a predictive model for first-line chemotherapy response.

Timeline

• Start date: 2024-06-21
• Primary completion: 2026-06-18
• Completion: 2026-06-18
• First posted: 2025-11-05
• Last updated: 2025-11-05

Locations

1 site across 1 country: United States