Blood test measuring cfDNA methylation 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

Observational City of Hope Medical Center · NCT07224815

This project will test whether a blood test that measures cfDNA 5mC/5hmC patterns can predict which people with metastatic colorectal cancer will respond to first-line FOLFOX or FOLFIRI chemotherapy.

Quick facts

Study typeObservational
Enrollment600 (estimated)
Ages18 Years and up
SexAll
SponsorCity of Hope Medical Center Academic / other
Drugs / interventionschemotherapy
Locations1 site (Duarte, California)
Trial IDNCT07224815 on ClinicalTrials.gov

What this trial studies

The EpiCORE program uses genome-wide profiling of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in circulating cell-free DNA to identify epigenetic signatures linked to response to first-line FOLFOX or FOLFIRI in metastatic colorectal cancer. In a discovery phase, researchers will sequence cfDNA 5mC/5hmC across the genome from pre-treatment plasma to find candidate regions associated with response. A training phase will apply targeted sequencing and modeling to refine predictive loci, followed by a validation phase using qPCR-based assays to confirm the finalized EpiCORE panel. Clinical response will be correlated with RECIST 1.1 or progression-free survival measures along with RAS/BRAF status to establish predictive performance.

Who should consider this trial

Good fit: Ideal candidates are people with histologically confirmed metastatic colorectal adenocarcinoma who received first-line FOLFOX or FOLFIRI, have available pre-treatment plasma or serum for cfDNA analysis, and have documented RAS/BRAF status and treatment response data.

Not a fit: Patients without adequate pre-treatment cfDNA samples, with non-adenocarcinoma histology, active inflammatory/autoimmune conditions that may alter cfDNA methylation, or concurrent malignancies requiring systemic therapy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, the test could let doctors select the most effective first-line chemotherapy sooner and spare patients from ineffective treatments.

How similar studies have performed: Early research on cfDNA methylation and hydroxymethylation has shown promise for tumor detection and monitoring, but this specific approach to predict chemotherapy response in metastatic colorectal cancer still requires validation in larger cohorts.

Eligibility criteria

Show full inclusion / exclusion criteria
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.

Where this trial is running

Duarte, California

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions CRCColorectal cancer5mC5hmCRAS/BRAF mutationFOLFOXFOLFIRIhydroxymethylation
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.