NCT07224841

Development of a cfDNA 5mC/5hmC-based Biomarker Panel to Predict Targeted Therapy Efficacy in mCRC

Development of a cfDNA 5mC/5hmC-based Epigenetic Biomarker Panel to Identify Determinants of Response In VEGF/EGFR-targeted Therapy for Metastatic Colorectal Cancer

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 500 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The EpiDRIVE study aims to identify cfDNA-based epigenetic determinants of response in metastatic colorectal cancer (mCRC) patients treated with EGFR- or VEGF-targeted therapy. By integrating 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiling, this study seeks to develop a predictive biomarker panel capable of differentiating responders from non-responders to targeted therapy.

Detailed description

Metastatic colorectal cancer (mCRC) remains one of the leading causes of cancer-related death. Although targeted agents such as anti-EGFR (cetuximab, panitumumab) and anti-VEGF (bevacizumab) therapies have improved survival, treatment response varies widely even among molecularly defined subgroups. Traditional biomarkers, including RAS/BRAF mutation and tumor sidedness, fail to accurately predict therapeutic efficacy. Recent studies highlight the potential of cell-free DNA (cfDNA) methylation (5mC) and hydroxymethylation (5hmC) as sensitive, non-invasive indicators of tumor biology and treatment dynamics. The EpiDRIVE study integrates cfDNA 5mC/5hmC sequencing and targeted validation to discover and verify epigenetic determinants of therapeutic response. Discovery phase: Whole-genome 5mC/5hmC profiling to identify differentially modified regions between responders and non-responders. Training phase: Targeted sequencing to establish a predictive cfDNA epigenetic panel (EpiDRIVE panel). Validation phase: qPCR-based validation of selected markers in an independent cohort to confirm predictive accuracy. This study aims to provide a non-invasive biomarker framework to predict and monitor efficacy of EGFR- and VEGF-targeted therapies in mCRC, ultimately guiding personalized treatment selection.

Conditions

• CRC (Colorectal Cancer)

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	cfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase)	High-throughput genome-wide sequencing of cfDNA methylation (5mC) and hydroxymethylation (5hmC) profiles from pre-treatment plasma samples in the discovery cohort to identify epigenetic determinants of targeted-therapy response (PFS ≥ 12 months vs \< 12 months).
DIAGNOSTIC_TEST	EpiDRIVE Assay (Targeted Sequencing / qPCR Validation)	Targeted sequencing or qPCR-based validation of cfDNA 5mC/5hmC markers identified from the discovery phase to develop and validate a predictive biomarker model discriminating patients with long vs short progression-free survival after EGFR-/VEGF-targeted therapy.

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