Development of a cfDNA 5mC/5hmC-based Epigenetic Biomarker Panel to Identify Determinants of Response In VEGF/EGFR-targeted Therapy for Metastatic Colorectal Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS) according to cfDNA 5mC/5hmC biomarker profile
研究概览
简要总结
The EpiDRIVE study aims to identify cfDNA-based epigenetic determinants of response in metastatic colorectal cancer (mCRC) patients treated with EGFR- or VEGF-targeted therapy.
By integrating 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiling, this study seeks to develop a predictive biomarker panel capable of differentiating responders from non-responders to targeted therapy.
详细描述
Metastatic colorectal cancer (mCRC) remains one of the leading causes of cancer-related death. Although targeted agents such as anti-EGFR (cetuximab, panitumumab) and anti-VEGF (bevacizumab) therapies have improved survival, treatment response varies widely even among molecularly defined subgroups.
Traditional biomarkers, including RAS/BRAF mutation and tumor sidedness, fail to accurately predict therapeutic efficacy.
Recent studies highlight the potential of cell-free DNA (cfDNA) methylation (5mC) and hydroxymethylation (5hmC) as sensitive, non-invasive indicators of tumor biology and treatment dynamics.
The EpiDRIVE study integrates cfDNA 5mC/5hmC sequencing and targeted validation to discover and verify epigenetic determinants of therapeutic response.
Discovery phase: Whole-genome 5mC/5hmC profiling to identify differentially modified regions between responders and non-responders.
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 EGFR-targeted therapy (cetuximab/panitumumab) or VEGF-targeted therapy (bevacizumab).
- •Availability of pre-treatment plasma sample for cfDNA analysis.
- •Documented radiologic response evaluation (RECIST 1.1).
- •RAS/BRAF mutation status known.
排除标准
- •Inadequate cfDNA quality or low cfDNA yield.
- •Non-adenocarcinoma histology.
- •Concurrent or prior other active malignancy.
- •Active inflammatory or autoimmune disease affecting cfDNA methylation profiles.
研究组 & 干预措施
Discovery Cohort - Long PFS Group (Responder)
Patients with metastatic colorectal cancer (mCRC) who received EGFR- or VEGF-targeted therapy and achieved a progression-free survival (PFS) ≥ 12 months, classified as clinical responders.
Pre-treatment plasma cfDNA samples were analyzed by genome-wide 5mC/5hmC sequencing to identify epigenetic determinants associated with durable treatment response.
干预措施: cfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase) (Diagnostic Test)
Discovery Cohort - Short PFS Group (Non-Responder)
Patients with mCRC who received EGFR- or VEGF-targeted therapy and showed progression-free survival (PFS) < 12 months, classified as non-responders.
Pre-treatment cfDNA samples were analyzed using genome-wide 5mC/5hmC sequencing and compared with long-PFS responders to identify differential methylation and hydroxymethylation patterns associated with resistance.
干预措施: cfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase) (Diagnostic Test)
Training Cohort - Long PFS Group (Responder)
Independent mCRC cohort with PFS ≥ 12 months following EGFR- or VEGF-targeted therapy.
Candidate cfDNA 5mC/5hmC markers identified in the discovery phase were validated using targeted sequencing (EpiDRIVE assay) to construct the predictive epigenetic biomarker panel.
干预措施: EpiDRIVE Assay (Targeted Sequencing / qPCR Validation) (Diagnostic Test)
Training Cohort - Short PFS Group (Non-Responder)
Independent mCRC patients with PFS < 12 months after targeted therapy. Targeted sequencing using the EpiDRIVE assay was conducted to refine and optimize the predictive model by comparing short- vs long-PFS cases.
干预措施: EpiDRIVE Assay (Targeted Sequencing / qPCR Validation) (Diagnostic Test)
Validation Cohort - Long PFS Group (Responder)
Separate validation cohort of mCRC patients achieving PFS ≥ 12 months under EGFR- or VEGF-targeted therapy.
qPCR-based EpiDRIVE assay was used to confirm predictive accuracy of the cfDNA 5mC/5hmC biomarker panel in identifying durable responders.
干预措施: EpiDRIVE Assay (Targeted Sequencing / qPCR Validation) (Diagnostic Test)
Validation Cohort - Short PFS Group (Non-Responder)
Independent validation cohort of mCRC patients with PFS < 12 months after targeted therapy.
cfDNA was analyzed using the qPCR-based EpiDRIVE assay to assess model specificity and distinguish non-responders from long-term responders.
干预措施: EpiDRIVE Assay (Targeted Sequencing / qPCR Validation) (Diagnostic Test)
结局指标
主要结局
Progression-Free Survival (PFS) according to cfDNA 5mC/5hmC biomarker profile
时间窗: Up to 36 months from therapy initiation
Progression-free survival (PFS) among patients with metastatic colorectal cancer (mCRC) receiving EGFR- or VEGF-targeted therapy, stratified by cfDNA 5mC/5hmC-based biomarker status.
次要结局
- Overall Survival (OS)(Up to 60 months from therapy initiation)