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

ConditionCRC (Colorectal Cancer)
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorCity of Hope Medical Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Disqualifiers

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.

Trial population

Patients diagnosed with Stage IV colorectal adenocarcinoma who received EGFR-targeted or VEGF-targeted therapy and had available pre-treatment plasma samples for cfDNA analysis.

Trial design

Design model

Case-control

Time perspective

Retrospective

Treatments tested in this trial

  • 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.

Treatment groups

500 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Discovery Cohort - Long PFS Group (Responder)1 intervention
Group B: Discovery Cohort - Short PFS Group (Non-Responder)1 intervention
Group C: Training Cohort - Long PFS Group (Responder)1 intervention
Group D: Training Cohort - Short PFS Group (Non-Responder)1 intervention
Group E: Validation Cohort - Long PFS Group (Responder)1 intervention
Group F: Validation Cohort - Short PFS Group (Non-Responder)1 intervention

Trial outcomes

Primary outcomes

1

Progression-Free Survival (PFS) according to cfDNA 5mC/5hmC biomarker profile

Progression-free survival (PFS) among patients with metastatic colorectal cancer (mCRC) receiving EGFR- or VEGF-targeted therapy, stratified by cfDNA 5mC/5hmC-based biomarker status.

Time frame
Up to 36 months from therapy initiation

Secondary outcomes

1

Overall Survival (OS)

Time from initiation of EGFR- or VEGF-targeted therapy to death from any cause. Overall survival will be analyzed in relation to cfDNA 5mC/5hmC biomarker-defined groups (high vs low EpiDRIVE score) to assess whether epigenetic cfDNA profiles are associated with differences in survival outcomes.

Time frame
Up to 60 months from therapy initiation

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

City of Hope Medical Center

Lead sponsor

Source ClinicalTrials.gov
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