[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07224724":3,"trial-entities:NCT07224724":116,"trial-summary:NCT07224724":120},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":6,"overall_status":7,"completion_date":8,"status_verified_date":9,"last_update_date":10,"start_date":11,"sponsor_name":12,"lead_sponsor_class":13,"has_dmc":14,"brief_summary":15,"detailed_description":16,"conditions":17,"keywords":20,"study_type":25,"primary_purpose":26,"phases":27,"enrollment_info":28,"interventions":31,"primary_outcomes":40,"secondary_outcomes":45,"sex":52,"minimum_age":53,"maximum_age":26,"healthy_volunteers":14,"eligibility_criteria":54,"std_ages":66,"locations":69,"central_contacts":84,"overall_officials":86,"references":89,"see_also_links":115},"NCT07224724","23228\u002FEXELION","Exosome-derived Extrahepatic Metastasis Detection By Liquid Biopsy In Colorectal Cancer Liver Metastases","RECRUITING","2028-06-18","2026-07","2026-07-07","2024-06-01","City of Hope Medical Center","OTHER",false,"Colorectal cancer is the third most common malignancy worldwide, and prognosis largely depends on how effectively metastatic disease is managed. The liver is the most frequent and prognostically important site of metastasis, and patients responding well to chemotherapy may become candidates for curative hepatic resection. However, the presence of extrahepatic metastasis (EHM) critically influences treatment eligibility and survival. Although clinical scores such as the Fong and Beppu systems include EHM as a determinant, its detection by imaging remains limited, especially for small or occult lesions. Accurate identification of EHM is also essential when considering liver transplantation for unresectable colorectal liver metastases (CRLM), where EHM remains an exclusion criterion.\n\nThe EXELION Study aims to develop a non-invasive diagnostic model using serum exosomal microRNAs (miRNAs) to detect both hepatic and extrahepatic metastases in patients with CRLM. By integrating circulating miRNA profiling with machine learning-based analysis, this study seeks to supplement imaging diagnostics, improve treatment stratification, and enhance clinical decision-making for metastatic colorectal cancer.","Despite improvements in diagnostic imaging-such as CT, MRI, and PET-CT-the sensitivity of EHM detection remains limited, particularly for small or occult lesions in the lung, peritoneum, or lymph nodes. As a result, patients may be inappropriately excluded from curative surgery or exposed to non-beneficial interventions. Thus, there is a pressing need for novel, non-invasive biomarkers capable of detecting EHM with higher accuracy than imaging alone.\n\nMicroRNAs (miRNAs), especially those encapsulated within exosomes, have emerged as stable and reproducible biomarkers reflecting tumor dynamics. Recent studies have shown that circulating miRNA signatures are associated with liver metastasis, therapeutic response, and recurrence risk in CRC. However, their utility for detecting extrahepatic metastasis has not yet been validated in clinical cohorts.\n\nIn this research effort, the investigators will leverage small RNA sequencing and machine learning to develop a predictive model for the presence of hepatic and extrahepatic metastases in patients with CRLM. The research plan will consist of three phases:\n\n1. A discovery phase, identifying candidate miRNAs associated with the presence of EHM using next-generation sequencing (NGS) or microarray-based profiling of serum exosomal miRNAs.\n2. A model development phase, establishing a quantitative reverse transcription PCR (RT-qPCR) assay and training a predictive algorithm.\n3. A validation phase, independently testing the predictive accuracy of the model in an external cohort.\n\nThis diagnostic framework is provisionally termed \"EXELION\" (Exosome-derived Extrahepatic Metastasis Detection by LIquid Biopsy in Colorectal Cancer Liver Metastases). At the end of this study, the EXELION assay is expected to serve as a non-invasive tool to assist clinical decision-making by accurately predicting the presence of extrahepatic metastasis in patients with CRLM.",[18,19],"Colorectal Cancer Liver Metastases (CRLM)","Metastatic Colorectal Carcinoma (mCRC)",[21,22,23,24],"CRC","Extrahepatic metastasis","liquid biopsy","Early detection","OBSERVATIONAL",null,[],{"count":29,"type":30},500,"ESTIMATED",[32],{"type":13,"name":33,"description":34,"armGroupLabels":35},"EXELION","A panel of exosomal microRNA, whose expression level is tested in serum or plasma",[36,37,38,39],"Extrahepatic liver metastasis patients(Training Cohort)","Non-extrahepatic liver metastasis patients (Training Cohort)","Non-extrahepatic liver metastasis patients (Validation Cohort)","Non-extrahepatic liver metastasis patients(Discovery Cohort)",[41],{"measure":42,"description":43,"timeFrame":44},"Sensitivity","True positive rate: the probability of a positive test result, conditioned on the individual truly being positive","Through study completion, an average of 1 year",[46,49],{"measure":47,"description":48,"timeFrame":44},"Specificity","True negative rate: the probability of a negative test result, conditioned on the individual truly being negative",{"measure":50,"description":51,"timeFrame":44},"Accuracy","A measure of trueness: proportion of correct predictions (both true positives and true negatives) among the total number of cases examined","ALL","18 Years",{"inclusion":55,"exclusion":61,"raw_text":65},[56,57,58,59,60],"Adults (≥18 years old)","Histologically- or cytologically-confirmed colorectal cancer that is metastatic","Availability of pre-treatment plasma samples","Written informed consent provided","Sufficient clinical and imaging data to determine presence\u002Fabsence of extrahepatic metastasis",[62,63,64],"Prior malignancies within 5 years","Poor sample quality or hemolysis","Inability to provide informed consent","Inclusion Criteria:\n\n* Adults (≥18 years old)\n* Histologically- or cytologically-confirmed colorectal cancer that is metastatic\n* Availability of pre-treatment plasma samples\n* Written informed consent provided\n* Sufficient clinical and imaging data to determine presence\u002Fabsence of extrahepatic metastasis\n\nExclusion Criteria:\n\n* Prior malignancies within 5 years\n* Poor sample quality or hemolysis\n* Inability to provide informed consent",[67,68],"ADULT","OLDER_ADULT",[70],{"facility":12,"status":7,"city":71,"state":72,"zip":73,"country":74,"contacts":75,"geoPoint":81},"Duarte","California","91010","United States",[76],{"name":77,"role":78,"phone":79,"email":80},"Ajay Goel, PhD","CONTACT","626-218-3452","AJGOEL@COH.ORG",{"lat":82,"lon":83},34.13945,-117.97729,[85],{"name":77,"role":78,"phone":79,"email":80},[87],{"name":77,"affiliation":12,"role":88},"PRINCIPAL_INVESTIGATOR",[90,94,97,100,103,106,109,112],{"pmid":91,"type":92,"citation":93},"39306468","BACKGROUND","Adam R, Piedvache C, Chiche L, Adam JP, Salame E, Bucur P, Cherqui D, Scatton O, Granger V, Ducreux M, Cillo U, Cauchy F, Mabrut JY, Verslype C, Coubeau L, Hardwigsen J, Boleslawski E, Muscari F, Jeddou H, Pezet D, Heyd B, Lucidi V, Geboes K, Lerut J, Majno P, Grimaldi L, Levi F, Lewin M, Gelli M; Collaborative TransMet group. Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): results from a multicentre, open-label, prospective, randomised controlled trial. Lancet. 2024 Sep 21;404(10458):1107-1118. doi: 10.1016\u002FS0140-6736(24)01595-2.",{"pmid":95,"type":92,"citation":96},"34212254","Giuliante F, Vigano L, De Rose AM, Mirza DF, Lapointe R, Kaiser G, Barroso E, Ferrero A, Isoniemi H, Lopez-Ben S, Popescu I, Ouellet JF, Hubert C, Regimbeau JM, Lin JK, Skipenko OG, Ardito F, Adam R. Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry. Ann Surg Oncol. 2021 Dec;28(13):8198-8208. doi: 10.1245\u002Fs10434-021-10220-w. Epub 2021 Jul 1.",{"pmid":98,"type":92,"citation":99},"19647200","Carpizo DR, D'Angelica M. Liver resection for metastatic colorectal cancer in the presence of extrahepatic disease. Lancet Oncol. 2009 Aug;10(8):801-9. doi: 10.1016\u002FS1470-2045(09)70081-6.",{"pmid":101,"type":92,"citation":102},"28009741","Leung U, Gonen M, Allen PJ, Kingham TP, DeMatteo RP, Jarnagin WR, D'Angelica MI. Colorectal Cancer Liver Metastases and Concurrent Extrahepatic Disease Treated With Resection. Ann Surg. 2017 Jan;265(1):158-165. doi: 10.1097\u002FSLA.0000000000001624.",{"pmid":104,"type":92,"citation":105},"38942992","Bojmar L, Zambirinis CP, Hernandez JM, Chakraborty J, Shaashua L, Kim J, Johnson KE, Hanna S, Askan G, Burman J, Ravichandran H, Zheng J, Jolissaint JS, Srouji R, Song Y, Choubey A, Kim HS, Cioffi M, van Beek E, Sigel C, Jessurun J, Velasco Riestra P, Blomstrand H, Jonsson C, Jonsson A, Lauritzen P, Buehring W, Ararso Y, Hernandez D, Vinagolu-Baur JP, Friedman M, Glidden C, Firmenich L, Lieberman G, Mejia DL, Nasar N, Mutvei AP, Paul DM, Bram Y, Costa-Silva B, Basturk O, Boudreau N, Zhang H, Matei IR, Hoshino A, Kelsen D, Sagi I, Scherz A, Scherz-Shouval R, Yarden Y, Oren M, Egeblad M, Lewis JS, Keshari K, Grandgenett PM, Hollingsworth MA, Rajasekhar VK, Healey JH, Bjornsson B, Simeone DM, Tuveson DA, Iacobuzio-Donahue CA, Bromberg J, Vincent CT, O'Reilly EM, DeMatteo RP, Balachandran VP, D'Angelica MI, Kingham TP, Allen PJ, Simpson AL, Elemento O, Sandstrom P, Schwartz RE, Jarnagin WR, Lyden D. Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer. Nat Med. 2024 Aug;30(8):2170-2180. doi: 10.1038\u002Fs41591-024-03075-7. Epub 2024 Jun 28.",{"pmid":107,"type":92,"citation":108},"37471075","Katipally RR, Martinez CA, Pugh SA, Bridgewater JA, Primrose JN, Domingo E, Maughan TS, Talamonti MS, Posner MC, Weichselbaum RR, Pitroda SP; with the S:CORT Consortium. Integrated Clinical-Molecular Classification of Colorectal Liver Metastases: A Biomarker Analysis of the Phase 3 New EPOC Randomized Clinical Trial. JAMA Oncol. 2023 Sep 1;9(9):1245-1254. doi: 10.1001\u002Fjamaoncol.2023.2535.",{"pmid":110,"type":92,"citation":111},"22267596","Mekenkamp LJ, Haan JC, Koopman M, Vink-Borger ME, Israeli D, Teerenstra S, Ylstra B, Meijer GA, Punt CJ, Nagtegaal ID. Chromosome 20p11 gains are associated with liver-specific metastasis in patients with colorectal cancer. Gut. 2013 Jan;62(1):94-101. doi: 10.1136\u002Fgutjnl-2011-301587. Epub 2012 Jan 20.",{"pmid":113,"type":92,"citation":114},"39466980","Mahuron KM, Hernandez MC, Wong P, Fan D, Ituarte PHG, Raoof M, Singh G, Fong Y, Melstrom LG. Liver Resection With Extrahepatic Disease: A Population-Based Analysis of Thoughtful Selection. J Surg Oncol. 2025 Mar;131(3):443-449. doi: 10.1002\u002Fjso.27944. Epub 2024 Oct 28.",[],{"nct_id":4,"conditions":117,"biomarkers":119},[118],"Colorectal Carcinoma",[],{"nct_id":4,"found":121,"summary":122,"prompt_version":132},true,{"design":123,"status":124,"heading":125,"summary":126,"follow_up":127,"word_count":128,"commitments":129,"compensation":130,"drugs_mentioned":131},"This is an observational study, meaning participants are not given a specific treatment but are observed. It aims to enroll 500 participants.","completed","Detecting Extrahepatic Metastasis in Colorectal Cancer Liver Metastases","This study is looking for a better way to find if colorectal cancer (cancer that starts in the colon or rectum) that has spread to the liver has also spread to other parts of the body (extrahepatic metastasis). Currently, imaging tests sometimes miss these small or hidden cancer spots. Researchers are testing a new method called EXELION, which looks at tiny particles called exosomes in your blood. These exosomes contain microRNA, which can show how cancer is behaving. The goal is to see if EXELION can find these extra cancer spots more accurately than current methods. You may be able to join if you are an adult with confirmed metastatic colorectal cancer, have pre-treatment blood samples available, and have enough medical information to know if you have extrahepatic metastasis. The main goal is to see how well EXELION can detect these extra cancer spots.","The primary endpoint, sensitivity, will be measured through study completion, which is an average of 1 year.",144,"Not specified in the trial record.","Not stated in the trial record.",[33],"v2"]