Recruiting

FOLFOX & FOLFIRI

Sponsor:

City of Hope Medical Center

Code:

NCT07224815

Conditions

CRC (Colorectal Cancer)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

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

EpiCORE Assay (Targeted Sequencing / qPCR Validation)

Study Details

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.

Conditions

CRC (Colorectal Cancer)

Study ID

NCT07224815

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 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.

Study Design

Enrollment

600 participants

Anticipated

Interventions and Outcome Measures

Arms

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.

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.

Training Cohort - PFS ≥ 12 Months (Responder)

Independent mCRC cohort with long PFS (≥12M). Targeted sequencing (EpiCORE assay) to refine predictive markers.

Training Cohort - PFS < 12 Months (Non-Responder)

Independent mCRC cohort with short PFS (<12M). Targeted sequencing to validate resistance-associated markers.

Validation Cohort - PFS ≥ 12 Months (Responder)

Independent validation cohort analyzed with qPCR-based EpiCORE assay to confirm biomarker predictive accuracy.

Validation Cohort - PFS < 12 Months (Non-Responder)

Independent validation cohort with poor PFS analyzed to assess specificity and model performance.

Interventions

cfDNA 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).

EpiCORE 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.

Primary outcome measure

  • Progression-Free Survival (PFS) [ Time Frame: Up to 36 months from initiation of first-line chemotherapy ]

Central Contacts and Locations

Central contacts

Ajay Goel, PhD

6263598111ajgoel@coh.org

Locations

City of Hope Medical Center

Recruiting

Duarte, California, United States, 91010

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

  • CRC
  • Colorectal cancer
  • 5mC
  • 5hmC
  • RAS/BRAF mutation
  • FOLFOX
  • FOLFIRI
  • hydroxymethylation

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.