[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07586046":3,"trial-entities:NCT07586046":196,"trial-summary:NCT07586046":202},{"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":10,"sponsor_name":12,"lead_sponsor_class":13,"has_dmc":14,"brief_summary":15,"detailed_description":16,"conditions":17,"keywords":19,"study_type":24,"primary_purpose":25,"phases":26,"enrollment_info":28,"interventions":31,"primary_outcomes":38,"secondary_outcomes":47,"sex":60,"minimum_age":61,"maximum_age":62,"healthy_volunteers":63,"eligibility_criteria":64,"std_ages":92,"locations":95,"central_contacts":123,"overall_officials":126,"references":127,"see_also_links":195},"NCT07586046","STU00224943","Defining the Ablative Dose for Y-90 TARE","A Prospective Dose-Escalation Study to Define an Ablative Dose of Yttrium-90 Transarterial Radioembolization Using Advanced Dosimetry and Functional MRI (MARGIN Study)","NOT_YET_RECRUITING","2029-05","2026-05","2026-05-14","Northwestern University","OTHER",true,"This study is being done to help doctors improve how they treat liver tumors that cannot be removed by surgery or treated with standard ablation techniques. The researchers want to find out the best amount of radiation that needs to be delivered to completely destroy (or ablate) parts of the liver that have cancer.","Currently, doctors use Yttrium-90 (Y90) radiation segmentectomy, a treatment that delivers tiny radioactive beads into the blood vessels feeding the liver tumor. These beads give off radiation that helps kill the cancer cells from the inside, right where the tumor is located. This approach allows doctors to target the tumor very precisely, while keeping the rest of the liver as healthy as possible. However, the exact dose needed to fully ablate a tumor without damaging healthy liver tissue is not well established.\n\nTo answer this, the study team will use specialized imaging before and after treatment to evaluate how the radiation is distributed in the liver and how the liver responds over time. These include PET\u002FCT or PET\u002FMRI scans, which are standard medical imaging tests that are not considered experimental. During these scans, a small amount of a safe radioactive substance is injected into their vein. This helps show where the Y90 beads are in their liver.\n\nIn a PET\u002FCT scan, two types of imaging are performed during the same session. The PET scan detects signals from the radioactive substance and shows how your liver is functioning at a molecular level. The CT scan, which uses x-rays to create detailed cross-sectional images of the body, provides a precise anatomical map that helps localize these functional signals. Together, they give a clear picture of both the structure and activity within the liver.\n\nPET\u002FMRI works similarly but uses magnetic fields and radio waves instead of x-rays. It combines the functional information from the PET scan with the highly detailed soft-tissue images from MRI, which can be especially useful in evaluating the liver. Both imaging techniques are done during a single visit, with the PET component typically performed at the same time as the CT or MRI, depending on which machine is used. They will also have a liver MRI with dual contrast (Eovist and extracellular gadolinium), another standard imaging procedure. MRI uses magnets and radio waves to take detailed pictures of your liver. Eovist is a special dye injected into their vein during the scan that helps highlight liver tissue and shows how well different parts of their liver are functioning. Extracellular gadolinium is a more general contrast agent that enhances blood vessels and tissues, providing complementary information. This helps the doctors confirm whether the tumor area was completely treated.\n\nThe goal is to determine the safest and most effective dose of radiation to fully treat cancer while preserving healthy liver tissue. This information may help doctors treat future patients more precisely and safely.\n\nYttrium-90 and the imaging methods used in this study, including PET\u002FCT, PET\u002FMRI, and dual contrast MRI, are FDA-approved.",[18],"HCC - Hepatocellular Carcinoma",[20,21,22,23],"MARGIN","HCC","Y90","Liver Cancer","INTERVENTIONAL","TREATMENT",[27],"PHASE2",{"count":29,"type":30},30,"ESTIMATED",[32],{"type":13,"name":33,"description":34,"armGroupLabels":35},"Yttrium-90 Radiation Segmentectomy (Y90 RS) using glass microspheres","The objective of this study is to define an optimal \"ablative dose\" range for Y90 Radiation Segmentectomy that achieves complete sectoral ablation detectable on dual contrast MRI and to determine whether this dose-response relationship differs between cirrhotic and non-cirrhotic patients.",[36,37],"Cirrhotic","Non-cirrhotic",[39,43],{"measure":40,"description":41,"timeFrame":42},"Ablative Dose Threshold for Y90 Radiation Segmentectomy","To prospectively define the \"ablative dose\" threshold for Y90 Radiation Segmentectomy (RS) using post-treatment PET dosimetry and hepatobiliary phase MRI","From enrollment to the end of post-treatment Y90 12 month follow up visit",{"measure":44,"description":45,"timeFrame":46},"Impact of Cirrhosis on Ablative Dose Requirements","To determine whether cirrhotic patients require a higher threshold dose for ablation compared to non- cirrhotic patients","From enrollment to enrollment to post-treatment Y-90 12 month follow-up visit",[48,52,56],{"measure":49,"description":50,"timeFrame":51},"Correlation of Y90 Dose with Imaging Biomarkers","To evaluate the correlation between delivered Y90 dose and imaging biomarkers, including signal loss on hepatobiliary phase MRI, ablative margins, extracellular volume fraction, and perfusion changes","Assessed at 1, 4-9, and 12 month follow up visits",{"measure":53,"description":54,"timeFrame":55},"Tumor Response and Time-to-Progression Assessment","To assess tumor response by mRECIST and determine time to progression (TTP)","From enrollment to end of post-treatment Y-90 12 month follow up visit",{"measure":57,"description":58,"timeFrame":59},"Safety and Tolerability of Escalating Y90 Doses","To assess the safety and tolerability of escalating segmental Y90 doses (200- 500 Gy) using Bayesian optimal interval (BOIN) dose-escalation design under Data and Safety Monitoring Committee (DSMC) oversight","From enrollment to end of post-treatment Y90 12 month follow up visit","ALL","18 Years",null,false,{"inclusion":65,"exclusion":81,"raw_text":91},[66,67,68,69,70,71,72,73,74,75,76,77,78,79,80],"Diagnosis of hepatocellular carcinoma (HCC), cholangiocarcinoma, or liver-dominant metastatic disease not amenable to surgical resection or ablation.","Age ≥18 years.","Tumor size ≤5 cm requiring treatment of ≤2 Couinaud segments.","Child-Pugh class A or B liver function","Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.","Adequate organ and bone marrow function as defined below:","Leukocytes (WBC) ≥ 3,000\u002FmcL","Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL","Hemoglobin ≥ 9 g\u002FdL","Platelets ≥ 50,000\u002FmcL","Total bilirubin ≤ 3.0 mg\u002FdL","AST ≤ 100 U\u002FL, ALT ≤ 120 U\u002FL","Creatinine ≤ 2.0 mg\u002FdL or estimated GFR ≥ 40 mL\u002Fmin\u002F1.73 m²","Ability to undergo imaging and laboratory evaluations required by the study.","Ability to understand and willingness to sign a written informed consent document.",[82,83,84,85,86,87,88,89,90],"Extrahepatic metastases.","Pregnant or breastfeeding individuals.","Tumors requiring treatment of more than two Couinaud segments.","Known hypersensitivity to gadolinium-based contrast agents.","Contraindications to MRI (e.g., incompatible pacemakers, claustrophobia unresponsive to sedation).","Coagulopathy or clinical instability precluding angiographic intervention.","Prisoners or individuals under legal custody.","Adults unable to consent.","Individuals under 18 years of age.","Inclusion Criteria:\n\n* Diagnosis of hepatocellular carcinoma (HCC), cholangiocarcinoma, or liver-dominant metastatic disease not amenable to surgical resection or ablation.\n* Age ≥18 years.\n* Tumor size ≤5 cm requiring treatment of ≤2 Couinaud segments.\n* Child-Pugh class A or B liver function\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.\n* Adequate organ and bone marrow function as defined below:\n* Leukocytes (WBC) ≥ 3,000\u002FmcL\n* Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL\n* Hemoglobin ≥ 9 g\u002FdL\n* Platelets ≥ 50,000\u002FmcL\n* Total bilirubin ≤ 3.0 mg\u002FdL\n* AST ≤ 100 U\u002FL, ALT ≤ 120 U\u002FL\n* Creatinine ≤ 2.0 mg\u002FdL or estimated GFR ≥ 40 mL\u002Fmin\u002F1.73 m²\n* Ability to undergo imaging and laboratory evaluations required by the study.\n* Ability to understand and willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n* Extrahepatic metastases.\n* Pregnant or breastfeeding individuals.\n* Tumors requiring treatment of more than two Couinaud segments.\n* Known hypersensitivity to gadolinium-based contrast agents.\n* Contraindications to MRI (e.g., incompatible pacemakers, claustrophobia unresponsive to sedation).\n* Coagulopathy or clinical instability precluding angiographic intervention.\n* Prisoners or individuals under legal custody.\n* Adults unable to consent.\n* Individuals under 18 years of age.",[93,94],"ADULT","OLDER_ADULT",[96],{"facility":12,"city":97,"state":98,"zip":99,"country":100,"contacts":101,"geoPoint":120},"Chicago","Illinois","60611","United States",[102,107,111,113,116,118],{"name":103,"role":104,"phone":105,"email":106},"Andrew C Gordon, MD, PhD","CONTACT","(561)703-0134","andrew.gordon@nm.org",{"name":108,"role":104,"phone":109,"email":110},"Cameron Khakpour, BA","312-926-5509","cameron.khakpour@northwestern.edu",{"name":103,"role":112},"PRINCIPAL_INVESTIGATOR",{"name":114,"role":115},"Robert J Lewandowski, MD, FSIR","SUB_INVESTIGATOR",{"name":117,"role":115},"Amir A Borhani, MD",{"name":119,"role":115},"Saad E Abu Zahra, MD",{"lat":121,"lon":122},41.85003,-87.65005,[124,125],{"name":103,"role":104,"phone":105,"email":106},{"name":108,"role":104,"phone":109,"email":110},[],[128,132,135,138,141,144,147,150,153,156,159,162,165,168,171,174,177,180,183,186,189,192],{"pmid":129,"type":130,"citation":131},"33189539","BACKGROUND","Gordon AC, Gates VL, White SB, Harris KR, Procissi D, Zhang Z, Li W, Samaan D, Nicolai JR, Mouli SK, Sato KT, Ryu RK, Omary RA, Salem R, Lewandowski RJ, Larson AC. Correlation and Agreement of Yttrium-90 Positron Emission Tomography\u002FComputed Tomography with Ex Vivo Radioembolization Microsphere Deposition in the Rabbit VX2 Liver Tumor Model. J Vasc Interv Radiol. 2021 Jan;32(1):23-32.e1. doi: 10.1016\u002Fj.jvir.2020.09.016. Epub 2020 Nov 12.",{"pmid":133,"type":130,"citation":134},"29944086","Luetkens JA, Klein S, Traber F, Schmeel FC, Sprinkart AM, Kuetting DLR, Block W, Uschner FE, Schierwagen R, Hittatiya K, Kristiansen G, Gieseke J, Schild HH, Trebicka J, Kukuk GM. Quantification of Liver Fibrosis at T1 and T2 Mapping with Extracellular Volume Fraction MRI: Preclinical Results. Radiology. 2018 Sep;288(3):748-754. doi: 10.1148\u002Fradiol.2018180051. Epub 2018 Jun 26.",{"pmid":136,"type":130,"citation":137},"33216180","Syed M, Shah J, Montazeri SA, Grajo JR, Geller B, Toskich B. Analysis of dynamic hepatobiliary contrast-enhanced MRI signal intensity after Yttrium-90 radioembolization with glass microspheres for the treatment of hepatocellular carcinoma. Abdom Radiol (NY). 2021 May;46(5):2182-2187. doi: 10.1007\u002Fs00261-020-02855-2. Epub 2020 Nov 20.",{"pmid":139,"type":130,"citation":140},"34597229","Borhani AA, Elsayes KM, Catania R, Kambadakone A, Furlan A, Kierans AS, Kamath A, Harmath C, Horvat N, Humar A, Kielar AZ. Imaging Evaluation of Living Liver Donor Candidates: Techniques, Protocols, and Anatomy. Radiographics. 2021 Oct;41(6):1572-1591. doi: 10.1148\u002Frg.2021210012.",{"pmid":142,"type":130,"citation":143},"20233824","Riaz A, Miller FH, Kulik LM, Nikolaidis P, Yaghmai V, Lewandowski RJ, Mulcahy MF, Ryu RK, Sato KT, Gupta R, Wang E, Baker T, Abecassis M, Benson AB 3rd, Nemcek AA Jr, Omary R, Salem R. Imaging response in the primary index lesion and clinical outcomes following transarterial locoregional therapy for hepatocellular carcinoma. JAMA. 2010 Mar 17;303(11):1062-9. doi: 10.1001\u002Fjama.2010.262.",{"pmid":145,"type":130,"citation":146},"19133645","Riaz A, Kulik L, Lewandowski RJ, Ryu RK, Giakoumis Spear G, Mulcahy MF, Abecassis M, Baker T, Gates V, Nayar R, Miller FH, Sato KT, Omary RA, Salem R. Radiologic-pathologic correlation of hepatocellular carcinoma treated with internal radiation using yttrium-90 microspheres. Hepatology. 2009 Apr;49(4):1185-93. doi: 10.1002\u002Fhep.22747.",{"pmid":148,"type":130,"citation":149},"33166497","Garin E, Tselikas L, Guiu B, Chalaye J, Edeline J, de Baere T, Assenat E, Tacher V, Robert C, Terroir-Cassou-Mounat M, Mariano-Goulart D, Amaddeo G, Palard X, Hollebecque A, Kafrouni M, Regnault H, Boudjema K, Grimaldi S, Fourcade M, Kobeiter H, Vibert E, Le Sourd S, Piron L, Sommacale D, Laffont S, Campillo-Gimenez B, Rolland Y; DOSISPHERE-01 Study Group. Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial. Lancet Gastroenterol Hepatol. 2021 Jan;6(1):17-29. doi: 10.1016\u002FS2468-1253(20)30290-9. Epub 2020 Nov 7.",{"pmid":151,"type":130,"citation":152},"25678490","Garin E, Rolland Y, Edeline J, Icard N, Lenoir L, Laffont S, Mesbah H, Breton M, Sulpice L, Boudjema K, Rohou T, Raoul JL, Clement B, Boucher E. Personalized dosimetry with intensification using 90Y-loaded glass microsphere radioembolization induces prolonged overall survival in hepatocellular carcinoma patients with portal vein thrombosis. J Nucl Med. 2015 Mar;56(3):339-46. doi: 10.2967\u002Fjnumed.114.145177. Epub 2015 Feb 12.",{"pmid":154,"type":130,"citation":155},"33839262","Mouli SK, Raiter S, Harris K, Mylarapu A, Burks M, Li W, Gordon AC, Khan A, Matsumoto M, Bailey KL, Pasciak AS, Manupipatpong S, Weiss CR, Casalino D, Miller FH, Gates VL, Hohlastos E, Lewandowski RJ, Kim DH, Dreher MR, Salem R. Yttrium-90 Radioembolization to the Prostate Gland: Proof of Concept in a Canine Model and Clinical Translation. J Vasc Interv Radiol. 2021 Aug;32(8):1103-1112.e12. doi: 10.1016\u002Fj.jvir.2021.01.282. Epub 2021 Apr 9.",{"pmid":157,"type":130,"citation":158},"21149493","Gates VL, Esmail AA, Marshall K, Spies S, Salem R. Internal pair production of 90Y permits hepatic localization of microspheres using routine PET: proof of concept. J Nucl Med. 2011 Jan;52(1):72-6. doi: 10.2967\u002Fjnumed.110.080986. Epub 2010 Dec 13.",{"pmid":160,"type":130,"citation":161},"21976634","Kao YH, Tan EH, Lim KY, Ng CE, Goh SW. Yttrium-90 internal pair production imaging using first generation PET\u002FCT provides high-resolution images for qualitative diagnostic purposes. Br J Radiol. 2012 Jul;85(1015):1018-9. doi: 10.1259\u002Fbjr\u002F33524085. Epub 2011 Oct 5.",{"pmid":163,"type":130,"citation":164},"23405207","Elschot M, Vermolen BJ, Lam MG, de Keizer B, van den Bosch MA, de Jong HW. Quantitative comparison of PET and Bremsstrahlung SPECT for imaging the in vivo yttrium-90 microsphere distribution after liver radioembolization. PLoS One. 2013;8(2):e55742. doi: 10.1371\u002Fjournal.pone.0055742. Epub 2013 Feb 6.",{"pmid":166,"type":130,"citation":167},"33739462","Salem R, Johnson GE, Kim E, Riaz A, Bishay V, Boucher E, Fowers K, Lewandowski R, Padia SA. Yttrium-90 Radioembolization for the Treatment of Solitary, Unresectable HCC: The LEGACY Study. Hepatology. 2021 Nov;74(5):2342-2352. doi: 10.1002\u002Fhep.31819. Epub 2021 Jun 11.",{"pmid":169,"type":130,"citation":170},"32749512","Gabr A, Riaz A, Johnson GE, Kim E, Padia S, Lewandowski RJ, Salem R. Correlation of Y90-absorbed radiation dose to pathological necrosis in hepatocellular carcinoma: confirmatory multicenter analysis in 45 explants. Eur J Nucl Med Mol Imaging. 2021 Feb;48(2):580-583. doi: 10.1007\u002Fs00259-020-04976-8. Epub 2020 Aug 4.",{"pmid":172,"type":130,"citation":173},"39709122","Gupta AN, Serhal M, Gordon AC, Gabr A, Kalyan A, Kulik L, Sato KT, Riaz A, Hohlastos ES, Salem R, Lewandowski RJ. Radiation Segmentectomy and Modified Radiation Lobectomy for Unresectable Early-Stage Intrahepatic Cholangiocarcinoma. J Vasc Interv Radiol. 2025 Apr;36(4):650-659. doi: 10.1016\u002Fj.jvir.2024.12.016. Epub 2024 Dec 19.",{"pmid":175,"type":130,"citation":176},"24691943","Vouche M, Habib A, Ward TJ, Kim E, Kulik L, Ganger D, Mulcahy M, Baker T, Abecassis M, Sato KT, Caicedo JC, Fryer J, Hickey R, Hohlastos E, Lewandowski RJ, Salem R. Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: multicenter radiology-pathology correlation and survival of radiation segmentectomy. Hepatology. 2014 Jul;60(1):192-201. doi: 10.1002\u002Fhep.27057. Epub 2014 May 27.",{"pmid":178,"type":130,"citation":179},"20421150","Riaz A, Gates VL, Atassi B, Lewandowski RJ, Mulcahy MF, Ryu RK, Sato KT, Baker T, Kulik L, Gupta R, Abecassis M, Benson AB 3rd, Omary R, Millender L, Kennedy A, Salem R. Radiation segmentectomy: a novel approach to increase safety and efficacy of radioembolization. Int J Radiat Oncol Biol Phys. 2011 Jan 1;79(1):163-71. doi: 10.1016\u002Fj.ijrobp.2009.10.062. Epub 2010 Apr 24.",{"pmid":181,"type":130,"citation":182},"27575820","Salem R, Gordon AC, Mouli S, Hickey R, Kallini J, Gabr A, Mulcahy MF, Baker T, Abecassis M, Miller FH, Yaghmai V, Sato K, Desai K, Thornburg B, Benson AB, Rademaker A, Ganger D, Kulik L, Lewandowski RJ. Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma. Gastroenterology. 2016 Dec;151(6):1155-1163.e2. doi: 10.1053\u002Fj.gastro.2016.08.029. Epub 2016 Aug 27.",{"pmid":184,"type":130,"citation":185},"15918147","Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis. 2005;25(2):181-200. doi: 10.1055\u002Fs-2005-871198.",{"pmid":187,"type":130,"citation":188},"21992124","El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011 Sep 22;365(12):1118-27. doi: 10.1056\u002FNEJMra1001683. No abstract available.",{"pmid":190,"type":130,"citation":191},"12016426","Befeler AS, Di Bisceglie AM. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology. 2002 May;122(6):1609-19. doi: 10.1053\u002Fgast.2002.33411.",{"pmid":193,"type":130,"citation":194},"33538338","Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322\u002Fcaac.21660. Epub 2021 Feb 4.",[],{"nct_id":4,"conditions":197,"biomarkers":201},[198,199,200],"Cholangiocarcinoma","Hepatocellular Carcinoma","Metastatic Malignant Neoplasm",[],{"nct_id":4,"found":14,"summary":203,"prompt_version":213},{"design":204,"status":205,"heading":206,"summary":207,"follow_up":208,"word_count":209,"commitments":210,"compensation":211,"drugs_mentioned":212},"This is an interventional study with a planned enrollment of 30 participants. It is designed to define an optimal \"ablative dose\" range for Y90 Radiation Segmentectomy.","completed","Defining the Ablative Dose for Y-90 TARE in Liver Cancer","This study is investigating Yttrium-90 Radiation Segmentectomy (Y90 RS) using glass microspheres for liver tumors (Hepatocellular Carcinoma or HCC) that cannot be removed by surgery. Doctors want to find the best amount of radiation (ablative dose) needed to completely destroy parts of the liver with cancer, while keeping the rest of your liver healthy. They will also see if this dose is different for people with or without cirrhosis (scarring of the liver). Success for this study means finding the right dose that completely destroys the tumor area, which will be checked using special MRI scans. This study plans to enroll 30 participants, but its current status is unclear.","Participants will be followed for 12 months after treatment to assess the ablative dose threshold and the impact of cirrhosis on dose requirements.",109,"You would receive Yttrium-90 Radiation Segmentectomy. You would also have specialized imaging, including PET\u002FCT or PET\u002FMRI scans, before and after treatment to evaluate the radiation distribution and liver response.","Not stated in the trial record.",[33],"v2"]