Defining the Ablative Dose for Y-90 TARE

Официальное название

A Prospective Dose-Escalation Study to Define an Ablative Dose of Yttrium-90 Transarterial Radioembolization Using Advanced Dosimetry and Functional MRI (MARGIN Study)

Обзор

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.

Подробное описание

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 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 their vein. This helps show where the Y90 beads are in their 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 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.

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. 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.

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.

Вмешательства

• Другое 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.

Первичные конечные точки

• Ablative Dose Threshold for Y90 Radiation Segmentectomy [Срок оценки: From enrollment to the end of post-treatment Y90 12 month follow up visit]
• Impact of Cirrhosis on Ablative Dose Requirements [Срок оценки: From enrollment to enrollment to post-treatment Y-90 12 month follow-up visit]

Вторичные конечные точки (3)

• Correlation of Y90 Dose with Imaging Biomarkers [Срок оценки: Assessed at 1, 4-9, and 12 month follow up visits]
• Tumor Response and Time-to-Progression Assessment [Срок оценки: From enrollment to end of post-treatment Y-90 12 month follow up visit]
• Safety and Tolerability of Escalating Y90 Doses [Срок оценки: From enrollment to end of post-treatment Y90 12 month follow up visit]

Критерии участия

Критерии включения

• 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/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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Northwestern University — Chicago

Публикации

• 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: 10.1 PMID 33189539
• 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. PMID 29944086
• 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. PMID 33216180
• 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. PMID 34597229
• 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. PMID 20233824
• 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. PMID 19133645
• 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 ap PMID 33166497
• 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.11 PMID 25678490

Идентификаторы

NCT: NCT07586046 · STU00224943

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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