Recruiting

EGFR & VEGF-targeted Therapy

Sponsor:

City of Hope Medical Center

Code:

NCT07224841

Conditions

CRC (Colorectal Cancer)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

cfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase)

EpiDRIVE Assay (Targeted Sequencing / qPCR Validation)

Study Details

Brief 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.

Conditions

CRC (Colorectal Cancer)

Study ID

NCT07224841

Start date

Jun 21, 2024

Status verified date

Jul, 2026

Completion date

Jun 18, 2028

Anticipated

Primary completion date

Jun 18, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

500 participants

Anticipated

Interventions and Outcome Measures

Arms

Discovery Cohort - Long PFS Group (Responder)

Patients with metastatic colorectal cancer (mCRC) who received EGFR- or VEGF-targeted therapy and achieved a progression-free survival (PFS) ≥ 12 months, classified as clinical responders.

Pre-treatment plasma cfDNA samples were analyzed by genome-wide 5mC/5hmC sequencing to identify epigenetic determinants associated with durable treatment response.

Discovery Cohort - Short PFS Group (Non-Responder)

Patients with mCRC who received EGFR- or VEGF-targeted therapy and showed progression-free survival (PFS) < 12 months, classified as non-responders.

Pre-treatment cfDNA samples were analyzed using genome-wide 5mC/5hmC sequencing and compared with long-PFS responders to identify differential methylation and hydroxymethylation patterns associated with resistance.

Training Cohort - Long PFS Group (Responder)

Independent mCRC cohort with PFS ≥ 12 months following EGFR- or VEGF-targeted therapy.

Candidate cfDNA 5mC/5hmC markers identified in the discovery phase were validated using targeted sequencing (EpiDRIVE assay) to construct the predictive epigenetic biomarker panel.

Training Cohort - Short PFS Group (Non-Responder)

Independent mCRC patients with PFS < 12 months after targeted therapy. Targeted sequencing using the EpiDRIVE assay was conducted to refine and optimize the predictive model by comparing short- vs long-PFS cases.

Validation Cohort - Long PFS Group (Responder)

Separate validation cohort of mCRC patients achieving PFS ≥ 12 months under EGFR- or VEGF-targeted therapy.

qPCR-based EpiDRIVE assay was used to confirm predictive accuracy of the cfDNA 5mC/5hmC biomarker panel in identifying durable responders.

Validation Cohort - Short PFS Group (Non-Responder)

Independent validation cohort of mCRC patients with PFS < 12 months after targeted therapy.

cfDNA was analyzed using the qPCR-based EpiDRIVE assay to assess model specificity and distinguish non-responders from long-term responders.

Interventions

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).

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.

Primary outcome measure

  • Progression-Free Survival (PFS) according to cfDNA 5mC/5hmC biomarker profile [ Time Frame: Up to 36 months from therapy initiation ]

Central Contacts and Locations

Central contacts

Ajay Goel, PhD

626-359-8111ajgoel@coh.org

Locations

City of Hope Medical Center

Recruiting

Duarte, California, United States, 91016

Contacts

Ajay Goel, PhD

626-218-3452ajgoel@coh.org

More Information

Sponsor

City of Hope Medical Center

Last update posted

Jul 7, 2026

Last verified

Jul, 2026

Keywords

  • mCRC
  • Target therapy
  • 5mc/5hmc
  • 5-hydroxymethylation
  • Metastatic colorectal cancer
  • anti-EGFR therapy
  • anti-VEGF therapy
  • RAS/BRAF mutation
  • 5-methylcytosine

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by City of Hope Medical Center on 2026-07-07.