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

NCT07224815 | Recruiting

• 1 other identifier: 23228/EpiCORE
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

CRC (Colorectal Cancer)

Keywords

CRC; Colorectal cancer; 5mC; 5hmC; RAS/BRAF mutation; FOLFOX; FOLFIRI; hydroxymethylation

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  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 Outcomes (1)

• Overall Survival (OS):

  Up to 60 months from initiation of first-line chemotherapy

Study Arms (6)

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)

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)

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)

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)

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)

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)

Interventions

cfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase) DIAGNOSTIC_TEST

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); Discovery Cohort - PFS ≥ 12 Months (Responder)

EpiCORE Assay (Targeted Sequencing / qPCR Validation) DIAGNOSTIC_TEST

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); Training Cohort - PFS ≥ 12 Months (Responder); Validation Cohort - PFS < 12 Months (Non-Responder); Validation Cohort - PFS ≥ 12 Months (Responder)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Related Publications (17)

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MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Ajay Goel, PhD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ajay Goel, PhD

CONTACT

6263598111; ajgoel@coh.org

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2025
• First Posted: November 5, 2025
• Study Start: June 21, 2024
• Primary Completion (Estimated): June 18, 2026
• Study Completion (Estimated): June 18, 2026
• Last Updated: November 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)