[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07266363":3,"trial-entities:NCT07266363":139,"trial-summary:NCT07266363":143},{"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":25,"primary_purpose":26,"phases":27,"enrollment_info":28,"interventions":31,"primary_outcomes":51,"secondary_outcomes":56,"sex":65,"minimum_age":66,"maximum_age":26,"healthy_volunteers":67,"eligibility_criteria":68,"std_ages":80,"locations":83,"central_contacts":98,"overall_officials":100,"references":103,"see_also_links":138},"NCT07266363","23228\u002FSYNERGY","Integrated Cf-miRNA and Exosomal miRNA Signature for Early Detection of Esophageal Squamous Cell Carcinoma","SYNERGY Study: Early Detection Through Integrated Evaluation of Cell-Free and Exosomal microRNAs for Biomarker-Guided Screening of Esophageal Squamous Cell Carcinoma","RECRUITING","2028-06-18","2026-07","2026-07-07","2025-01-15","City of Hope Medical Center","OTHER",false,"Esophageal squamous cell carcinoma (ESCC) remains a highly lethal cancer worldwide, largely due to late diagnosis. Current screening methods such as upper endoscopy are invasive, operator-dependent, and limited in their ability to detect early-stage lesions.\n\nTo address this clinical need, the SYNERGY study seeks to develop a non-invasive, blood-based biomarker assay that integrates cell-free microRNAs (cf-miRNAs) and exosomal microRNAs (exo-miRNAs) to detect ESCC at an early and potentially curable stage.\n\nThis multicenter translational study includes discovery, training, and validation phases using preoperative plasma or serum samples. By combining the tumor specificity of exosomal miRNAs with the systemic sensitivity of cf-miRNAs, SYNERGY aims to construct a robust diagnostic model with high sensitivity and specificity for early ESCC detection.","Esophageal cancer is the 11th most common cancer globally and the 7th leading cause of cancer-related death, with an estimated 511,000 new cases and 445,000 deaths annually. ESCC accounts for the majority of cases worldwide. Despite advances in endoscopy and therapy, outcomes for advanced ESCC remain poor, highlighting the pressing need for sensitive, minimally invasive early detection strategies.\n\nExosomal miRNAs (exo-miRNAs) are selectively released by tumor cells and remain stable in circulation, enabling reliable detection of tumor-specific signals. Cell-free miRNAs (cf-miRNAs) circulate broadly and can reflect overall tumor burden, metastatic spread, and microenvironmental changes.\n\nPrevious ESCC biomarker studies were limited by small validation cohorts and reliance on tissue-based public datasets that do not fully capture circulating biomarker patterns. The SYNERGY study addresses these limitations through comprehensive discovery analysis and multi-cohort blood-based validation.",[19],"ESCC",[21,22,23,24],"Exosomal miRNAs","Cell-free miRNAs","Esophageal squamous cell carcinoma","Liquid biopsy","OBSERVATIONAL",null,[],{"count":29,"type":30},600,"ESTIMATED",[32,39,45],{"type":33,"name":34,"description":35,"armGroupLabels":36},"DIAGNOSTIC_TEST","Small RNA sequencing of exo- and cf-miRNAs","Identification of differentially expressed cf-miRNAs",[37,38],"Discovery cohort (ESCC)","Discovery cohort (NDC)",{"type":33,"name":40,"description":41,"armGroupLabels":42},"RT-qPCR quantification of cf- and exo-miRNAs (SYNERGY assay)","RT-qPCR quantification of cf- and exo-miRNAs, and construction of machine learning classifier",[43,44],"Testing cohort (ESCC)","Testing cohort (NDC)",{"type":33,"name":46,"description":47,"armGroupLabels":48},"PCR-based validation (SYNERGY assay)","PCR-based validation of the SYNERGY miRNA panel",[49,50],"Training cohort (ESCC)","Training cohort (NDC)",[52],{"measure":53,"description":54,"timeFrame":55},"Sensitivity","Comparison of Pathological Diagnosis and the SYNERGY Assay","At study completion, an average of one year",[57,61],{"measure":58,"description":59,"timeFrame":60},"AUC","AUC of integrated cf- + exo-miRNA model","At Study completion, an average of one year",{"measure":62,"description":63,"timeFrame":64},"Specificity","Description: Comparison of Pathological Diagnosis and the SYNERGY Assay","Time Frame: At study completion, , an average of one year","ALL","18 Years",true,{"inclusion":69,"exclusion":74,"raw_text":79},[70,71,72,73],"Adults age 18 to 90 years","Histologically confirmed esophageal squamous cell carcinoma","No prior systemic therapy before sample collection","For control groups: absence of malignant disease",[75,76,77,78],"Lack of informed consent","Inadequate sample volume or RNA quality","Prior cancer within 5 years (except localized cancers)","Active systemic inflammation that may alter circulating RNA profiles","Inclusion Criteria:\n\n* Adults age 18 to 90 years\n* Histologically confirmed esophageal squamous cell carcinoma\n* No prior systemic therapy before sample collection\n* For control groups: absence of malignant disease\n\nExclusion Criteria:\n\n* Lack of informed consent\n* Inadequate sample volume or RNA quality\n* Prior cancer within 5 years (except localized cancers)\n* Active systemic inflammation that may alter circulating RNA profiles",[81,82],"ADULT","OLDER_ADULT",[84],{"facility":13,"status":8,"city":85,"state":86,"zip":87,"country":88,"contacts":89,"geoPoint":95},"Monrovia","California","91016","United States",[90],{"name":91,"role":92,"phone":93,"email":94},"Ajay Goel, PhD","CONTACT","626-218-3452","ajgoel@coh.org",{"lat":96,"lon":97},34.14806,-117.99895,[99],{"name":91,"role":92,"phone":93,"email":94},[101],{"name":91,"affiliation":13,"role":102},"PRINCIPAL_INVESTIGATOR",[104,108,111,114,117,120,123,126,129,132,135],{"pmid":105,"type":106,"citation":107},"30387125","BACKGROUND","Mao Y, Fu Z, Zhang Y, Dong L, Zhang Y, Zhang Q, Li X, Wang C. A six-microRNA risk score model predicts prognosis in esophageal squamous cell carcinoma. J Cell Physiol. 2019 May;234(5):6810-6819. doi: 10.1002\u002Fjcp.27429. Epub 2018 Nov 1.",{"pmid":109,"type":106,"citation":110},"38956246","Li T, Sun G, Ye H, Song C, Shen Y, Cheng Y, Zou Y, Fang Z, Shi J, Wang K, Dai L, Wang P. ESCCPred: a machine learning model for diagnostic prediction of early esophageal squamous cell carcinoma using autoantibody profiles. Br J Cancer. 2024 Sep;131(5):883-894. doi: 10.1038\u002Fs41416-024-02781-w. Epub 2024 Jul 2.",{"pmid":112,"type":106,"citation":113},"37399999","Li K, Lin Y, Zhou Y, Xiong X, Wang L, Li J, Zhou F, Guo Y, Chen S, Chen Y, Tang H, Qiu X, Cai S, Zhang D, Bremer E, Jim Yeung SC, Zhang H. Salivary Extracellular MicroRNAs for Early Detection and Prognostication of Esophageal Cancer: A Clinical Study. Gastroenterology. 2023 Oct;165(4):932-945.e9. doi: 10.1053\u002Fj.gastro.2023.06.021. Epub 2023 Jul 1.",{"pmid":115,"type":106,"citation":116},"35148754","Miyoshi J, Zhu Z, Luo A, Toden S, Zhou X, Izumi D, Kanda M, Takayama T, Parker IM, Wang M, Gao F, Zaidi AH, Baba H, Kodera Y, Cui Y, Wang X, Liu Z, Goel A. A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study. Mol Cancer. 2022 Feb 11;21(1):44. doi: 10.1186\u002Fs12943-022-01507-x.",{"pmid":118,"type":106,"citation":119},"39849483","Chen J, Zheng Y, Wang Z, Gao Q, Hao K, Chen X, Ke N, Lv X, Weng J, Zhong Y, Huang Z, Fu M, Zhao L, Lin F, Mi H, Tang H, Yu C, Huang Y. Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma. BMC Med. 2025 Jan 23;23(1):39. doi: 10.1186\u002Fs12916-025-03871-z.",{"pmid":121,"type":106,"citation":122},"36153105","Codipilly DC, Wang KK. Squamous Cell Carcinoma of the Esophagus. Gastroenterol Clin North Am. 2022 Sep;51(3):457-484. doi: 10.1016\u002Fj.gtc.2022.06.005. Epub 2022 Aug 29.",{"pmid":124,"type":106,"citation":125},"21296855","Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322\u002Fcaac.20107. Epub 2011 Feb 4.",{"pmid":127,"type":106,"citation":128},"29709526","Codipilly DC, Qin Y, Dawsey SM, Kisiel J, Topazian M, Ahlquist D, Iyer PG. Screening for esophageal squamous cell carcinoma: recent advances. Gastrointest Endosc. 2018 Sep;88(3):413-426. doi: 10.1016\u002Fj.gie.2018.04.2352. Epub 2018 Apr 27.",{"pmid":130,"type":106,"citation":131},"39182610","Chen J, Liu X, Zhang Z, Su R, Geng Y, Guo Y, Zhang Y, Su M. Early Diagnostic Markers for Esophageal Squamous Cell Carcinoma: Copy Number Alteration Gene Identification and cfDNA Detection. Lab Invest. 2024 Oct;104(10):102127. doi: 10.1016\u002Fj.labinv.2024.102127. Epub 2024 Aug 23.",{"pmid":133,"type":106,"citation":134},"41088482","Ma L, Dou L, Liu Y, Zhang Y, Liu X, Ng HL, Chu J, Liu Y, Li Z, Ke Y, Liu S, He S, Wang G. Development and validation of predictive models combining cell-Free DNA motifs and protein biomarkers for early detection of esophageal squamous cell carcinoma and precancerous lesion. Biomark Res. 2025 Oct 14;13(1):126. doi: 10.1186\u002Fs40364-025-00840-9.",{"pmid":136,"type":106,"citation":137},"39725880","Zheng Y, Xing W, BingWei, Liu X, Liang G, Yuan D, Yang K, Wang W, Chen D, Ma J. Detection of a novel DNA methylation marker panel for esophageal cancer diagnosis using circulating tumor DNA. BMC Cancer. 2024 Dec 26;24(1):1578. doi: 10.1186\u002Fs12885-024-13301-7.",[],{"nct_id":4,"conditions":140,"biomarkers":142},[141],"Esophageal Squamous Cell Carcinoma",[],{"nct_id":4,"found":67,"summary":144,"prompt_version":154},{"design":145,"status":146,"heading":147,"summary":148,"follow_up":149,"word_count":150,"commitments":151,"compensation":152,"drugs_mentioned":153},"This is an observational study, meaning researchers will collect and analyze samples without giving any new treatments. It aims to enroll 600 participants.","completed","SYNERGY Study: Early Detection of Esophageal Squamous Cell Carcinoma","This study, called SYNERGY, is looking for better ways to find esophageal squamous cell carcinoma (ESCC), a type of cancer, early. Currently, ESCC is often found late, making it harder to treat. Researchers are testing a non-invasive (no surgery needed) blood test that looks at tiny genetic materials called cell-free microRNAs (cf-miRNAs) and exosomal microRNAs (exo-miRNAs) in your blood. The goal is to see if these can help detect ESCC at an earlier stage when it might be more curable. They will use different lab tests, including Small RNA sequencing, RT-qPCR quantification, and PCR-based validation, to identify these miRNAs. The study aims to enroll 600 adults, aged 18 to 90, who have been diagnosed with ESCC or are healthy controls without cancer. Success will be measured by how well the test can correctly identify people with ESCC.","The primary endpoint, sensitivity, will be measured at study completion, which is an average of one year.",137,"Not specified in the trial record.","Not stated in the trial record.",[],"v2"]