Clinical trial · Observational
Development of a cfDNA 5mC/5hmC-based Biomarker Panel to Predict Targeted Therapy Efficacy in mCRC
Development of a cfDNA 5mC/5hmC-based Epigenetic Biomarker Panel to Identify Determinants of Response In VEGF/EGFR-targeted Therapy for Metastatic Colorectal Cancer
NCT07224841CI-TRIAL-00117129EpiDRIVErecruitingClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| CRC (Colorectal Cancer) | Colorectal Carcinoma | ALIAS | 0.85 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| cfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase) | Diagnostic Test | — | UNRESOLVED |
| EpiDRIVE Assay (Targeted Sequencing / qPCR Validation) | Diagnostic Test | — | UNRESOLVED |
Design
Arms and outcomes
Arms (6)
- label
- Discovery Cohort - Long PFS Group (Responder)
- description
- 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.
- interventionNames
- Diagnostic Test: cfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase)
- label
- Discovery Cohort - Short PFS Group (Non-Responder)
- description
- 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.
- interventionNames
- Diagnostic Test: cfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase)
- label
- Training Cohort - Long PFS Group (Responder)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * 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. Exclusion Criteria: * 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.
References
Publications (15)
- BACKGROUNDXu C, Mannucci A, Esposito F, Oliveres H, Alonso-Orduna V, Yubero A, Fernandez-Martos C, Salud A, Gallego J, Martin-Richard M, Fernandez-Plana J, Guillot M, Aparicio J, Fakih M, Kopetz S, Feliu J, Maurel J, Goel A. An Exosome-Based Liquid Biopsy Predicts Depth of Response and Survival Outcomes to Cetuximab and Panitumumab in Metastatic Colorectal Cancer: The EXONERATE Study. Clin Cancer Res. 2025 Mar 17;31(6):1002-1015. doi: 10.1158/1078-0432.CCR-24-1934. PMID 39820673
- BACKGROUNDKoroukian SM, Booker BD, Vu L, Schumacher FR, Rose J, Cooper GS, Selfridge JE, Markt SC. Receipt of Targeted Therapy and Survival Outcomes in Patients With Metastatic Colorectal Cancer. JAMA Netw Open. 2023 Jan 3;6(1):e2250030. doi: 10.1001/jamanetworkopen.2022.50030. PMID 36656585
- BACKGROUNDTirendi S, Marengo B, Domenicotti C, Bassi AM, Almonti V, Vernazza S. Colorectal cancer and therapy response: a focus on the main mechanisms involved. Front Oncol. 2023 Jul 19;13:1208140. doi: 10.3389/fonc.2023.1208140. eCollection 2023. PMID 37538108
- BACKGROUNDXie YH, Chen YX, Fang JY. Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther. 2020 Mar 20;5(1):22. doi: 10.1038/s41392-020-0116-z. PMID 32296018
- BACKGROUNDCai Z, Zhang J, He Y, Xia L, Dong X, Chen G, Zhou Y, Hu X, Zhong S, Wang Y, Chen H, Xie D, Liu X, Liu J. Liquid biopsy by combining 5-hydroxymethylcytosine signatures of plasma cell-free DNA and protein biomarkers for diagnosis and prognosis of hepatocellular carcinoma. ESMO Open. 2021 Feb;6(1):100021. doi: 10.1016/j.esmoop.2020.100021. Epub 2021 Jan 25. PMID 33508734
- BACKGROUNDZeng C, Stroup EK, Zhang Z, Chiu BC, Zhang W. Towards precision medicine: advances in 5-hydroxymethylcytosine cancer biomarker discovery in liquid biopsy. Cancer Commun (Lond). 2019 Mar 29;39(1):12. doi: 10.1186/s40880-019-0356-x. PMID 30922396