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

November 3, 2025 updated by: City of Hope Medical Center

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

600

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients diagnosed with Stage IV colorectal adenocarcinoma who received first-line FOLFOX or FOLFIRI chemotherapy and have available pre-treatment serum or plasma samples for cfDNA analysis.

Description

Inclusion Criteria:

  • Histologically confirmed metastatic colorectal adenocarcinoma (mCRC).
  • Received first-line chemotherapy (FOLFOX or FOLFIRI).
  • Availability of pre-treatment serum or plasma samples for cfDNA 5mC/5hmC analysis.
  • Documented radiologic or clinical response evaluation (RECIST 1.1 or PFS-based).
  • RAS/BRAF mutation status available.

Exclusion Criteria:

  • Inadequate cfDNA yield or poor DNA quality.
  • Non-adenocarcinoma histology.
  • Active inflammatory or autoimmune disease that may alter cfDNA methylation.
  • Concomitant malignancy requiring systemic therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Discovery Cohort - PFS ≥ 12 Months (Responder)

Patients with mCRC who achieved progression-free survival ≥ 12 months after first-line chemotherapy (FOLFOX or FOLFIRI).

cfDNA 5mC/5hmC sequencing performed to identify epigenetic determinants of durable response.
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).
Discovery Cohort - PFS < 12 Months (Non-Responder)

Patients with progression-free survival < 12 months after first-line chemotherapy.

Compared with responders to identify epigenetic features associated with resistance.
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).
Training Cohort - PFS ≥ 12 Months (Responder)
Independent mCRC cohort with long PFS (≥12M). Targeted sequencing (EpiCORE assay) to refine predictive markers.
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.
Training Cohort - PFS < 12 Months (Non-Responder)
Independent mCRC cohort with short PFS (<12M). Targeted sequencing to validate resistance-associated markers.
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.
Validation Cohort - PFS ≥ 12 Months (Responder)
Independent validation cohort analyzed with qPCR-based EpiCORE assay to confirm biomarker predictive accuracy.
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.
Validation Cohort - PFS < 12 Months (Non-Responder)
Independent validation cohort with poor PFS analyzed to assess specificity and model performance.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: Up to 36 months from initiation of first-line chemotherapy

Progression-free survival (PFS) is defined as the time from initiation of first-line chemotherapy (FOLFOX or FOLFIRI) to the date of documented disease progression or death from any cause, whichever occurs first.

The primary objective of the EpiCORE study is to evaluate whether cfDNA 5mC/5hmC-based biomarker profiles (EpiCORE panel) are associated with differences in PFS among patients with metastatic colorectal cancer (mCRC).
Up to 36 months from initiation of first-line chemotherapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS):
Time Frame: Up to 60 months from initiation of first-line chemotherapy
Time from chemotherapy initiation to death from any cause
Up to 60 months from initiation of first-line chemotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Investigators

  • Principal Investigator: Ajay Goel, PhD, City of Hope Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 21, 2024

Primary Completion (Estimated)

June 18, 2026

Study Completion (Estimated)

June 18, 2026

Study Registration Dates

First Submitted

November 3, 2025

First Submitted That Met QC Criteria

November 3, 2025

First Posted (Estimated)

November 5, 2025

Study Record Updates

Last Update Posted (Estimated)

November 5, 2025

Last Update Submitted That Met QC Criteria

November 3, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23228/EpiCORE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data collected for the study will be made available to others, including de-identified participant data, at publication, via a signed data access agreement and at the discretion of the investigators' approval of the proposed use of such data.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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