Development of a cfDNA 5mC/5hmC-based Epigenetic Biomarker Panel to Predict Chemotherapy Efficacy in Metastatic Colorectal Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 600
- 试验地点
- 2
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: 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).
次要结局
- Overall Survival (OS):(Up to 60 months from initiation of first-line chemotherapy)