CRC (Colorectal Cancer)
Conditions
Keywords
CRC, Colorectal cancer, 5mC, 5hmC, RAS/BRAF mutation, FOLFOX, FOLFIRI, hydroxymethylation
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. Training phase: Targeted sequencing and model construction based on candidate loci. Validation phase: qPCR-based testing to confirm predictive accuracy of the finalized EpiCORE panel. This study aims to establish a robust cfDNA biomarker framework for predicting and monitoring chemotherapy response in mCRC, contributing to individualized therapeutic decision-making.
Interventions
DIAGNOSTIC_TESTcfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase)
Genome-wide profiling of cfDNA methylation and hydroxymethylation from pre-treatment plasma to identify molecular determinants associated with chemotherapy efficacy (PFS ≥ 12M vs \< 12M).
DIAGNOSTIC_TESTEpiCORE Assay (Targeted Sequencing / qPCR Validation)
Targeted validation of cfDNA 5mC/5hmC markers from discovery phase using sequencing and qPCR to build and validate a predictive model for first-line chemotherapy response.
Sponsors
City of Hope Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS): | Up to 60 months from initiation of first-line chemotherapy | Time from chemotherapy initiation to death from any cause |
Countries
United States
Contacts
CONTACTAjay Goel, PhD
PRINCIPAL_INVESTIGATORAjay Goel, PhD
City of Hope Medical Center
Outcome results
None listed