Defining the Ablative Dose for Y-90 TARE (MARGIN)
10 septembre 2026 mis à jour par: Andrew Gordon, Northwestern University
A Prospective Dose-Escalation Study to Define an Ablative Dose of Yttrium-90 Transarterial Radioembolization Using Advanced Dosimetry and Functional MRI (MARGIN Study)
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.
Aperçu de l'étude
Statut
Recrutement
Les conditions
Intervention / Traitement
Description détaillée
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.
To 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 imaging procedures include PET/CT or PET/MRI 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 a participant's vein. This helps show where the Y90 beads are located in the participant's liver.
In a PET/CT scan, two types of imaging are performed during the same session. The PET scan detects signals from the radioactive substance and shows how the participant's 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.
PET/MRI 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. Participants will also undergo a liver MRI with dual contrast using Eovist and extracellular gadolinium, another standard imaging procedure. MRI uses magnets and radio waves to take detailed pictures of the liver. Eovist is a special dye injected into a participant's vein during the scan that helps highlight liver tissue and shows how well different parts of the liver are functioning. Extracellular gadolinium is a more general contrast agent that enhances blood vessels and tissues, providing complementary information. This imaging helps the doctors confirm whether the tumor area was completely treated.
The 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.
Yttrium-90 and the imaging methods used in this study, including PET/CT, PET/MRI, and dual contrast MRI, are FDA-approved.
Type d'étude
Interventionnel
Inscription (Estimé)
30
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Coordonnées de l'étude
- Nom: Andrew C Gordon, MD, PhD
- Numéro de téléphone: (561)703-0134
- E-mail: andrew.gordon@nm.org
Sauvegarde des contacts de l'étude
- Nom: Saad Abu Zahra, MD
- Numéro de téléphone: 646-996-2817
- E-mail: saad.abuzahra@northwestern.edu
Lieux d'étude
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-
Illinois
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Chicago, Illinois, États-Unis, 60611
- Recrutement
- Northwestern University
-
Contact:
- Andrew C Gordon, MD, PhD
- Numéro de téléphone: (561)703-0134
- E-mail: andrew.gordon@nm.org
-
Chercheur principal:
- Andrew C Gordon, MD, PhD
-
Sous-enquêteur:
- Robert J Lewandowski, MD, FSIR
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Sous-enquêteur:
- Amir A Borhani, MD
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Sous-enquêteur:
- Saad E Abu Zahra, MD
-
Contact:
- Saad Abu Zahra, MD
- Numéro de téléphone: 646-996-2817
- E-mail: saad.abuzahra@northwestern.edu
-
-
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Non
La description
Inclusion Criteria:
- Diagnosis of hepatocellular carcinoma (HCC), cholangiocarcinoma, or liver-dominant metastatic disease not amenable to surgical resection or ablation.
- Age ≥18 years.
- 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/mcL
- Absolute neutrophil count (ANC) ≥ 1,500/mcL
- Hemoglobin ≥ 9 g/dL
- Platelets ≥ 50,000/mcL
- Total bilirubin ≤ 3.0 mg/dL
- AST ≤ 100 U/L, ALT ≤ 120 U/L
- Creatinine ≤ 2.0 mg/dL or estimated GFR ≥ 40 mL/min/1.73 m²
- Ability to undergo imaging and laboratory evaluations required by the study.
- Ability to understand and willingness to sign a written informed consent document.
Exclusion Criteria:
- 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.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Comparateur actif: Cirrhotic
Cirrhotic patients will begin at 300 Gy.
Dose escalation will proceed in 100 Gy increments within each arm, with safety continuously evaluated by the Data Safety Monitoring Committee
|
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.
|
|
Comparateur actif: Non-cirrhotic
Non-cirrhotic patients will begin at a dose of 200 Gy.
Dose escalation will proceed in 100 Gy increments within each arm, with safety continuously evaluated by the Data Safety Monitoring Committee.
|
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.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Ablative Dose Threshold for Y90 Radiation Segmentectomy
Délai: From enrollment to the end of post-treatment Y90 12 month follow up visit
|
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
|
|
Impact of Cirrhosis on Ablative Dose Requirements
Délai: From enrollment to enrollment to post-treatment Y-90 12 month follow-up visit
|
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
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Correlation of Y90 Dose with Imaging Biomarkers
Délai: Assessed at 1, 4-9, and 12 month follow up visits
|
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
|
|
Tumor Response and Time-to-Progression Assessment
Délai: From enrollment to end of post-treatment Y-90 12 month follow up visit
|
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
|
|
Safety and Tolerability of Escalating Y90 Doses
Délai: From enrollment to end of post-treatment Y90 12 month follow up visit
|
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
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Pathologic Necrosis in Explanted Tumors
Délai: From enrollment to end of post-treatment Y90 12 month follow-up visit
|
To evaluate complete pathological necrosis in explanted tumors from patients who undergo liver resection or transplantation
|
From enrollment to end of post-treatment Y90 12 month follow-up visit
|
|
Early Imaging Biomarkers for Ablation Success
Délai: From enrollment to post-treatment Y90 12 month follow-up visit
|
To identify novel early imaging biomarkers (Eovist hepatobiliary phase defects, extracellular volume mapping, perfusion changes) that may serve as surrogates for ablation success
|
From enrollment to post-treatment Y90 12 month follow-up visit
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011 Sep 22;365(12):1118-27. doi: 10.1056/NEJMra1001683. No abstract available.
- Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis. 2005;25(2):181-200. doi: 10.1055/s-2005-871198.
- 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/caac.21660. Epub 2021 Feb 4.
- 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/jama.2010.262.
- Befeler AS, Di Bisceglie AM. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology. 2002 May;122(6):1609-19. doi: 10.1053/gast.2002.33411.
- 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/j.jvir.2021.01.282. Epub 2021 Apr 9.
- 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/S2468-1253(20)30290-9. Epub 2020 Nov 7.
- 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/Computed 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/j.jvir.2020.09.016. Epub 2020 Nov 12.
- 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/radiol.2018180051. Epub 2018 Jun 26.
- 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/s00261-020-02855-2. Epub 2020 Nov 20.
- 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/rg.2021210012.
- 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/hep.22747.
- 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/jnumed.114.145177. Epub 2015 Feb 12.
- 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/jnumed.110.080986. Epub 2010 Dec 13.
- Kao YH, Tan EH, Lim KY, Ng CE, Goh SW. Yttrium-90 internal pair production imaging using first generation PET/CT provides high-resolution images for qualitative diagnostic purposes. Br J Radiol. 2012 Jul;85(1015):1018-9. doi: 10.1259/bjr/33524085. Epub 2011 Oct 5.
- 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/journal.pone.0055742. Epub 2013 Feb 6.
- 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/hep.31819. Epub 2021 Jun 11.
- 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/s00259-020-04976-8. Epub 2020 Aug 4.
- 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/j.jvir.2024.12.016. Epub 2024 Dec 19.
- 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/hep.27057. Epub 2014 May 27.
- 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/j.ijrobp.2009.10.062. Epub 2010 Apr 24.
- 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/j.gastro.2016.08.029. Epub 2016 Aug 27.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
15 mai 2026
Achèvement primaire (Estimé)
1 février 2029
Achèvement de l'étude (Estimé)
1 mai 2029
Dates d'inscription aux études
Première soumission
7 mai 2026
Première soumission répondant aux critères de contrôle qualité
7 mai 2026
Première publication (Réel)
14 mai 2026
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
15 septembre 2026
Dernière mise à jour soumise répondant aux critères de contrôle qualité
10 septembre 2026
Dernière vérification
1 mai 2026
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Tumeurs par site
- Tumeurs
- Tumeurs par type histologique
- Tumeurs du système digestif
- Maladies du système digestif
- Maladies du foie
- Tumeurs, glandulaires et épithéliales
- Adénocarcinome
- Carcinome
- Conditions pathologiques, signes et symptômes
- Constatations morphologiques et microscopiques
- Carcinome hépatocellulaire
- Tumeurs du foie
- Marges d'excision
Autres numéros d'identification d'étude
- STU00224943
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
NON
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Non
Étudie un produit d'appareil réglementé par la FDA américaine
Non
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .