Development of a cfDNA 5mC/5hmC-based Epigenetic Biomarker Panel to Predict Chemotherapy Efficacy in Metastatic Colorectal Cancer
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 600
- Locations
- 1
- Primary Endpoint
- Progression-Free Survival (PFS)
Study Overview
Brief Summary
The EpiCORE study aims to identify cfDNA-based epigenetic markers predictive of response to first-line chemotherapy (FOLFOX or FOLFIRI) in metastatic colorectal cancer (mCRC).
By integrating 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiling, this study seeks to establish a non-invasive biomarker panel capable of distinguishing responders from non-responders.
Detailed Description
Despite the introduction of multi-agent chemotherapy regimens such as FOLFOX (5-FU, leucovorin, oxaliplatin) and FOLFIRI (5-FU, leucovorin, irinotecan), treatment outcomes in metastatic colorectal cancer (mCRC) remain highly variable.
Current predictive biomarkers, such as RAS/BRAF mutation or microsatellite instability, fail to accurately forecast response to cytotoxic chemotherapy.
Emerging evidence suggests that cfDNA methylation (5mC) and hydroxymethylation (5hmC) patterns reflect tumor biology and drug sensitivity, offering a promising avenue for precision chemotherapy.
The EpiCORE study integrates genome-wide 5mC/5hmC sequencing and targeted validation assays to identify and confirm epigenetic determinants of chemotherapy efficacy.
Discovery phase: Genome-wide 5mC/5hmC profiling of cfDNA from patients treated with first-line FOLFOX or FOLFIRI to identify candidate regions associated with treatment response.
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Retrospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Validation Cohort - PFS < 12 Months (Non-Responder)
Independent validation cohort with poor PFS analyzed to assess specificity and model performance.
Intervention: EpiCORE Assay (Targeted Sequencing / qPCR Validation) (Diagnostic Test)
Validation Cohort - PFS ≥ 12 Months (Responder)
Independent validation cohort analyzed with qPCR-based EpiCORE assay to confirm biomarker predictive accuracy.
Intervention: EpiCORE Assay (Targeted Sequencing / qPCR Validation) (Diagnostic Test)
Discovery Cohort - PFS ≥ 12 Months (Responder)
Patients with mCRC who achieved progression-free survival ≥ 12 months after first-line chemotherapy (FOLFOX or FOLFIRI).
cfDNA 5mC/5hmC sequencing performed to identify epigenetic determinants of durable response.
Intervention: cfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase) (Diagnostic Test)
Discovery Cohort - PFS < 12 Months (Non-Responder)
Patients with progression-free survival < 12 months after first-line chemotherapy.
Compared with responders to identify epigenetic features associated with resistance.
Intervention: cfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase) (Diagnostic Test)
Training Cohort - PFS ≥ 12 Months (Responder)
Independent mCRC cohort with long PFS (≥12M). Targeted sequencing (EpiCORE assay) to refine predictive markers.
Intervention: EpiCORE Assay (Targeted Sequencing / qPCR Validation) (Diagnostic Test)
Training Cohort - PFS < 12 Months (Non-Responder)
Independent mCRC cohort with short PFS (<12M). Targeted sequencing to validate resistance-associated markers.
Intervention: EpiCORE Assay (Targeted Sequencing / qPCR Validation) (Diagnostic Test)
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: Up to 36 months from initiation of first-line chemotherapy
Progression-free survival (PFS) is defined as the time from initiation of first-line chemotherapy (FOLFOX or FOLFIRI) to the date of documented disease progression or death from any cause, whichever occurs first. The primary objective of the EpiCORE study is to evaluate whether cfDNA 5mC/5hmC-based biomarker profiles (EpiCORE panel) are associated with differences in PFS among patients with metastatic colorectal cancer (mCRC).
Secondary Outcomes
- Overall Survival (OS):(Up to 60 months from initiation of first-line chemotherapy)