Development of a cfDNA 5mC/5hmC-based Biomarker Panel to Predict Targeted Therapy Efficacy in mCRC

Part of paid clinical trials in Duarte, California.

Sponsor
City of Hope Medical Center
Study ID
NCT07224841
Status
Recruiting
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Conditions

  • CRC (Colorectal Cancer)

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • cfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase) — DIAGNOSTIC_TEST
    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) — DIAGNOSTIC_TEST
    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.

Study Details

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.

Key Dates

Start date
Jun 21, 2024
Status verified
Nov 2025
Primary completion
Jun 18, 2026
Completion
Jun 18, 2026

Study Design

Enrollment
500 participants (estimated)

Arms

  • Arm: 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.
  • Arm: 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.
  • Arm: 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.
  • Arm: 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.
  • Arm: 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.
  • Arm: 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.

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

Locations (1)

FacilityCityStateZIPSite coordinators
City of Hope Medical CenterDuarteCalifornia91016
Ajay Goel, PhD
[email protected]
626-218-3452

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City of Hope Medical Center· Duarte, CA

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