cfDNA blood test using 5mC/5hmC to predict response to EGFR or VEGF targeted therapy in metastatic colorectal cancer

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

Observational City of Hope Medical Center · NCT07224841

This project will test if a blood test that measures cfDNA methylation (5mC/5hmC) can tell which people with metastatic colorectal cancer are likely to respond to EGFR- or VEGF-targeted treatments.

Quick facts

Study typeObservational
Enrollment500 (estimated)
Ages18 Years and up
SexAll
SponsorCity of Hope Medical Center Academic / other
Drugs / interventionscetuximab, panitumumab, bevacizumab
Locations1 site (Duarte, California)
Trial IDNCT07224841 on ClinicalTrials.gov

What this trial studies

The study collects pre-treatment plasma from patients with metastatic colorectal adenocarcinoma who received EGFR- or VEGF-targeted therapy and performs whole-genome 5mC/5hmC profiling to find differences between responders and non-responders. A targeted sequencing training phase will be used to build an EpiDRIVE cfDNA epigenetic panel, followed by qPCR-based validation of selected markers in an independent cohort. Clinical response is defined by documented radiologic evaluation (RECIST 1.1) and known RAS/BRAF status will be incorporated into analyses. The approach aims to produce a non-invasive biomarker panel that could complement existing molecular markers for therapy selection.

Who should consider this trial

Good fit: Ideal candidates are patients with histologically confirmed metastatic colorectal adenocarcinoma who received EGFR- or VEGF-targeted therapy, have a pre-treatment plasma sample available, and have known RAS/BRAF mutation status.

Not a fit: Patients without adequate cfDNA quantity/quality, with non-adenocarcinoma histology, concurrent active other malignancies, or active inflammatory/autoimmune conditions that alter cfDNA methylation profiles may not benefit from this approach.

Why it matters

Potential benefit: If successful, this could provide a simple blood test to help choose the most effective targeted drug and avoid ineffective treatments for people with metastatic colorectal cancer.

How similar studies have performed: Early research supports cfDNA methylation as a promising non-invasive marker, but combined 5mC/5hmC panels specifically for predicting targeted therapy response in mCRC remain exploratory and not yet widely validated.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Histologically confirmed metastatic colorectal adenocarcinoma (mCRC).
* Received EGFR-targeted therapy (cetuximab/panitumumab) or VEGF-targeted therapy (bevacizumab).
* Availability of pre-treatment plasma sample for cfDNA analysis.
* Documented radiologic response evaluation (RECIST 1.1).
* RAS/BRAF mutation status known.

Exclusion Criteria:

* Inadequate cfDNA quality or low cfDNA yield.
* Non-adenocarcinoma histology.
* Concurrent or prior other active malignancy.
* Active inflammatory or autoimmune disease affecting cfDNA methylation profiles.

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 CRCmCRCTarget therapy5mc/5hmc5-hydroxymethylationMetastatic colorectal canceranti-EGFR therapyanti-VEGF therapy
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.