[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07224841":3,"trial-entities:NCT07224841":149,"trial-summary:NCT07224841":153},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":20,"study_type":30,"primary_purpose":31,"phases":32,"enrollment_info":33,"interventions":36,"primary_outcomes":52,"secondary_outcomes":57,"sex":62,"minimum_age":63,"maximum_age":31,"healthy_volunteers":15,"eligibility_criteria":64,"std_ages":77,"locations":80,"central_contacts":95,"overall_officials":98,"references":101,"see_also_links":148},"NCT07224841","23228\u002FEpiDRIVE","Development of a cfDNA 5mC\u002F5hmC-based Biomarker Panel to Predict Targeted Therapy Efficacy in mCRC","Development of a cfDNA 5mC\u002F5hmC-based Epigenetic Biomarker Panel to Identify Determinants of Response In VEGF\u002FEGFR-targeted Therapy for Metastatic Colorectal Cancer","RECRUITING","2028-06-18","2026-07","2026-07-07","2024-06-21","City of Hope Medical Center","OTHER",false,"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.\n\nBy 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.","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.\n\nTraditional biomarkers, including RAS\u002FBRAF mutation and tumor sidedness, fail to accurately predict therapeutic efficacy.\n\nRecent 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.\n\nThe EpiDRIVE study integrates cfDNA 5mC\u002F5hmC sequencing and targeted validation to discover and verify epigenetic determinants of therapeutic response.\n\nDiscovery phase: Whole-genome 5mC\u002F5hmC profiling to identify differentially modified regions between responders and non-responders.\n\nTraining phase: Targeted sequencing to establish a predictive cfDNA epigenetic panel (EpiDRIVE panel).\n\nValidation phase: qPCR-based validation of selected markers in an independent cohort to confirm predictive accuracy.\n\nThis study aims to provide a non-invasive biomarker framework to predict and monitor efficacy of EGFR- and VEGF-targeted therapies in mCRC, ultimately guiding personalized treatment selection.",[19],"CRC (Colorectal Cancer)",[21,22,23,24,25,26,27,28,29],"mCRC","Target therapy","5mc\u002F5hmc","5-hydroxymethylation","Metastatic colorectal cancer","anti-EGFR therapy","anti-VEGF therapy","RAS\u002FBRAF mutation","5-methylcytosine","OBSERVATIONAL",null,[],{"count":34,"type":35},500,"ESTIMATED",[37,44],{"type":38,"name":39,"description":40,"armGroupLabels":41},"DIAGNOSTIC_TEST","cfDNA 5mC\u002F5hmC Sequencing (EpiDRIVE Discovery Phase)","High-throughput genome-wide sequencing of cfDNA methylation (5mC) and hydroxymethylation (5hmC) profiles from pre-treatment plasma samples in the discovery cohort to identify epigenetic determinants of targeted-therapy response (PFS ≥ 12 months vs \\\u003C 12 months).",[42,43],"Discovery Cohort - Long PFS Group (Responder)","Discovery Cohort - Short PFS Group (Non-Responder)",{"type":38,"name":45,"description":46,"armGroupLabels":47},"EpiDRIVE Assay (Targeted Sequencing \u002F qPCR Validation)","Targeted sequencing or qPCR-based validation of cfDNA 5mC\u002F5hmC markers identified from the discovery phase to develop and validate a predictive biomarker model discriminating patients with long vs short progression-free survival after EGFR-\u002FVEGF-targeted therapy.",[48,49,50,51],"Training Cohort - Long PFS Group (Responder)","Training Cohort - Short PFS Group (Non-Responder)","Validation Cohort - Long PFS Group (Responder)","Validation Cohort - Short PFS Group (Non-Responder)",[53],{"measure":54,"description":55,"timeFrame":56},"Progression-Free Survival (PFS) according to cfDNA 5mC\u002F5hmC biomarker profile","Progression-free survival (PFS) among patients with metastatic colorectal cancer (mCRC) receiving EGFR- or VEGF-targeted therapy, stratified by cfDNA 5mC\u002F5hmC-based biomarker status.","Up to 36 months from therapy initiation",[58],{"measure":59,"description":60,"timeFrame":61},"Overall Survival (OS)","Time from initiation of EGFR- or VEGF-targeted therapy to death from any cause. Overall survival will be analyzed in relation to cfDNA 5mC\u002F5hmC biomarker-defined groups (high vs low EpiDRIVE score) to assess whether epigenetic cfDNA profiles are associated with differences in survival outcomes.","Up to 60 months from therapy initiation","ALL","18 Years",{"inclusion":65,"exclusion":71,"raw_text":76},[66,67,68,69,70],"Histologically confirmed metastatic colorectal adenocarcinoma (mCRC).","Received EGFR-targeted therapy (cetuximab\u002Fpanitumumab) or VEGF-targeted therapy (bevacizumab).","Availability of pre-treatment plasma sample for cfDNA analysis.","Documented radiologic response evaluation (RECIST 1.1).","RAS\u002FBRAF mutation status known.",[72,73,74,75],"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.","Inclusion Criteria:\n\n* Histologically confirmed metastatic colorectal adenocarcinoma (mCRC).\n* Received EGFR-targeted therapy (cetuximab\u002Fpanitumumab) or VEGF-targeted therapy (bevacizumab).\n* Availability of pre-treatment plasma sample for cfDNA analysis.\n* Documented radiologic response evaluation (RECIST 1.1).\n* RAS\u002FBRAF mutation status known.\n\nExclusion Criteria:\n\n* Inadequate cfDNA quality or low cfDNA yield.\n* Non-adenocarcinoma histology.\n* Concurrent or prior other active malignancy.\n* Active inflammatory or autoimmune disease affecting cfDNA methylation profiles.",[78,79],"ADULT","OLDER_ADULT",[81],{"facility":13,"status":8,"city":82,"state":83,"zip":84,"country":85,"contacts":86,"geoPoint":92},"Duarte","California","91016","United States",[87],{"name":88,"role":89,"phone":90,"email":91},"Ajay Goel, PhD","CONTACT","626-218-3452","ajgoel@coh.org",{"lat":93,"lon":94},34.13945,-117.97729,[96],{"name":88,"role":89,"phone":97,"email":91},"626-359-8111",[99],{"name":88,"affiliation":13,"role":100},"PRINCIPAL_INVESTIGATOR",[102,106,109,112,115,118,121,124,127,130,133,136,139,142,145],{"pmid":103,"type":104,"citation":105},"39820673","BACKGROUND","Xu 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\u002F1078-0432.CCR-24-1934.",{"pmid":107,"type":104,"citation":108},"36656585","Koroukian 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\u002Fjamanetworkopen.2022.50030.",{"pmid":110,"type":104,"citation":111},"37538108","Tirendi 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\u002Ffonc.2023.1208140. eCollection 2023.",{"pmid":113,"type":104,"citation":114},"32296018","Xie 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\u002Fs41392-020-0116-z.",{"pmid":116,"type":104,"citation":117},"33508734","Cai 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\u002Fj.esmoop.2020.100021. Epub 2021 Jan 25.",{"pmid":119,"type":104,"citation":120},"30922396","Zeng 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\u002Fs40880-019-0356-x.",{"pmid":122,"type":104,"citation":123},"39393034","West-Szymanski DC, Zhang Z, Cui XL, Kowitwanich K, Gao L, Deng Z, Dougherty U, Williams C, Merkle S, He C, Zhang W, Bissonnette M. 5-Hydroxymethylated Biomarkers in Cell-Free DNA Predict Occult Colorectal Cancer up to 36 Months Before Diagnosis in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. JCO Precis Oncol. 2024 Oct;8:e2400277. doi: 10.1200\u002FPO.24.00277. Epub 2024 Oct 11.",{"pmid":125,"type":104,"citation":126},"38464122","West-Szymanski DC, Zhang Z, Cui XL, Kowitwanich K, Gao L, Deng Z, Dougherty U, Williams C, Merkle S, Moore M, He C, Bissonnette M, Zhang W. Machine learning identifies cell-free DNA 5-hydroxymethylation biomarkers that detect occult colorectal cancer in PLCO Screening Trial subjects. bioRxiv [Preprint]. 2024 Feb 26:2024.02.25.581955. doi: 10.1101\u002F2024.02.25.581955.",{"pmid":128,"type":104,"citation":129},"39817679","Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025 Jan-Feb;75(1):10-45. doi: 10.3322\u002Fcaac.21871. Epub 2025 Jan 16.",{"pmid":131,"type":104,"citation":132},"40055844","Song D, Zhang Z, Zheng J, Zhang W, Cai J. 5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation. Biomark Res. 2025 Mar 7;13(1):39. doi: 10.1186\u002Fs40364-025-00751-9.",{"pmid":134,"type":104,"citation":135},"40375296","Baldassarre G, L de la Serna I, Vallette FM. Death-ision: the link between cellular resilience and cancer resistance to treatments. Mol Cancer. 2025 May 15;24(1):144. doi: 10.1186\u002Fs12943-025-02339-1.",{"pmid":137,"type":104,"citation":138},"33930176","Ferrara R, Imbimbo M, Malouf R, Paget-Bailly S, Calais F, Marchal C, Westeel V. Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer. Cochrane Database Syst Rev. 2021 Apr 30;4(4):CD013257. doi: 10.1002\u002F14651858.CD013257.pub3.",{"pmid":140,"type":104,"citation":141},"38212123","Guler GD, Ning Y, Coruh C, Mognol GP, Phillips T, Nabiyouni M, Hazen K, Scott A, Volkmuth W, Levy S. Plasma cell-free DNA hydroxymethylation profiling reveals anti-PD-1 treatment response and resistance biology in non-small cell lung cancer. J Immunother Cancer. 2024 Jan 11;12(1):e008028. doi: 10.1136\u002Fjitc-2023-008028.",{"pmid":143,"type":104,"citation":144},"38667328","Shao J, Xu Y, Olsen RJ, Kasparian S, Sun K, Mathur S, Zhang J, He C, Chen SH, Bernicker EH, Li Z. 5-Hydroxymethylcytosine in Cell-Free DNA Predicts Immunotherapy Response in Lung Cancer. Cells. 2024 Apr 19;13(8):715. doi: 10.3390\u002Fcells13080715.",{"pmid":146,"type":104,"citation":147},"37904926","Li Q, Huang CC, Huang S, Tian Y, Huang J, Bitaraf A, Dong X, Nevalanen MT, Patel M, Wong J, Zhang J, Manley BJ, Park JY, Kohli M, Gore EM, Kilari D, Wang L. 5-hydroxymethylcytosine sequencing in plasma cell-free DNA identifies unique epigenomic features in prostate cancer patients resistant to androgen deprivation therapies. medRxiv [Preprint]. 2024 Oct 17:2023.10.13.23296758. doi: 10.1101\u002F2023.10.13.23296758.",[],{"nct_id":4,"conditions":150,"biomarkers":152},[151],"Colorectal Carcinoma",[],{"nct_id":4,"found":154,"summary":155,"prompt_version":165},true,{"design":156,"status":157,"heading":158,"summary":159,"follow_up":160,"word_count":161,"commitments":162,"compensation":163,"drugs_mentioned":164},"This is an observational study planning to include 500 participants with metastatic colorectal cancer. It is not a treatment study, but rather looks at existing data and samples.","completed","Observational Study on cfDNA Biomarkers for Targeted Therapy in mCRC","This observational study, called EpiDRIVE, is looking at how well targeted therapies like cetuximab, panitumumab, and bevacizumab work for people with metastatic colorectal cancer (mCRC). Researchers are studying your blood samples taken before treatment to find special markers in your cell-free DNA (cfDNA) that might predict if these treatments will be effective for you. They are looking at specific changes in your DNA called 5mC and 5hmC. The goal is to develop a test that can help doctors choose the best treatment for you. To join, you need to have mCRC, have received one of these targeted therapies, and have a pre-treatment blood sample available. The study will track how long you live without your cancer getting worse (Progression-Free Survival) for up to 36 months.","Your Progression-Free Survival will be measured for up to 36 months from when your therapy started.",125,"You would need to have a pre-treatment plasma sample available for cfDNA analysis. The study will also use your documented radiologic response evaluations.","Not stated in the trial record.",[],"v2"]