Epigenetic Signature for CRC Early Detection (epiCED)

City of Hope

Status: Active, not recruiting

Conditions: Early Detection of Cancer; DNA Methylation; Colorectal Cancer (Diagnosis); Non-cancer Controls; Cell Free DNA

Study type: Observational

Funder types: Other

Identifiers

NCT07224854

23228/epiCED

Details and patient eligibility

About

The epiCED is a noninvasive blood-based assay designed for early detection of colorectal cancer (CRC) using circulating cell-free DNA (cfDNA) 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) epigenetic markers. This study leverages retrospective, multi-center cohorts of CRC patients and non-cancer controls to discover and validate a robust cfDNA methylation signature. Small-scale sequencing and machine learning-based modeling will be applied to identify a minimal panel of methylation markers that can accurately discriminate CRC from non-cancer individuals, including early-stage disease. The ultimate goal is to develop a clinically practical, noninvasive screening tool that enables population-level early detection and improves patient outcomes.

Full description

The epiCED is a noninvasive, blood-based approach aimed at early detection of colorectal cancer (CRC) using circulating cell-free DNA (cfDNA) 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) epigenetic markers. Early detection of CRC is critical for improving patient outcomes, but current diagnostic tools-including colonoscopy, CT, and MRI-are either invasive, costly, or insufficiently sensitive for early-stage disease, limiting their use for population-wide screening.

This study will utilize retrospective, multi-center cohorts comprising adult participants (≥18 years) with confirmed CRC and non-cancer controls, including healthy volunteers and individuals with benign gastrointestinal conditions. Blood samples will be subjected to cfDNA extraction and small-scale epigenetic sequencing to profile 5mC and 5hmC patterns.

During the discovery phase, differential methylation analysis and machine learning-based feature selection will be applied to identify a minimal set of cfDNA methylation markers that optimally discriminate CRC from non-cancer individuals. In the training and validation phase, the identified signature will be evaluated across independent international multi-center cohorts to ensure reproducibility, robustness, and early-stage detection performance.

The primary objectives are to:

• Develop a cfDNA methylation panel capable of accurately distinguishing CRC patients from non-cancer controls.
• Validate the panel's ability to detect early-stage CRC.
• Secondary objectives include evaluating the association of the methylation signature with clinical parameters, tumor stage, and demographic factors. By integrating high-resolution cfDNA methylation profiling with advanced computational modeling, epiCED aims to provide a scalable, cost-effective, and clinically practical tool for noninvasive early detection of colorectal cancer.

Enrollment: 500 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Adults aged ≥18 years at the time of sample collection.
• Patients with confirmed CRC or non-cancer controls.
• Availability of retrospective blood samples collected according to institutional protocols.
• Willingness to allow use of de-identified clinical and demographic data.

Exclusion criteria

• Concurrent malignancies outside the gastrointestinal tract (unless in complete remission ≥5 years).
• Samples with insufficient volume or poor cfDNA quality.
• Recent chemotherapy, radiotherapy, or major surgery within 4 weeks prior to blood collection (if prospective samples).
• Any condition precluding reliable sample analysis or participation.

Trial design

500 participants in 2 patient groups

CRC

Description:

Adult patients with confirmed colorectal cancer from international centers.

Control

Description:

Non-cancer individuals, including healthy volunteers or patients with benign gastrointestinal conditions.