Defining the Ablative Dose for Y-90 TARE

NCT07586046 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: STU00224943
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HCC - Hepatocellular Carcinoma

Keywords

MARGIN; HCC; Y90; Liver Cancer

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (3)

• Correlation of Y90 Dose with Imaging Biomarkers

  Assessed at 1, 4-9, and 12 month follow up visits

• Tumor Response and Time-to-Progression Assessment

  From enrollment to end of post-treatment Y-90 12 month follow up visit

• Safety and Tolerability of Escalating Y90 Doses

  From enrollment to end of post-treatment Y90 12 month follow up visit

Other Outcomes (2)

• Pathologic Necrosis in Explanted Tumors

  From enrollment to end of post-treatment Y90 12 month follow-up visit

• Early Imaging Biomarkers for Ablation Success

  From enrollment to post-treatment Y90 12 month follow-up visit

Study Arms (2)

Cirrhotic

ACTIVE COMPARATOR

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

Other: Yttrium-90 Radiation Segmentectomy (Y90 RS) using glass microspheres

Non-cirrhotic

ACTIVE COMPARATOR

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.

Other: Yttrium-90 Radiation Segmentectomy (Y90 RS) using glass microspheres

Interventions

Yttrium-90 Radiation Segmentectomy (Y90 RS) using glass microspheres OTHER

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.

Cirrhotic; Non-cirrhotic

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Northwestern University: lead
• Radiological Society of North America: collaborator
• Northwestern University Feinberg School of Medicine: collaborator
• Robert H. Lurie Cancer Center: collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (22)

• 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.

  PMID: 33189539 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 33166497 BACKGROUND

• 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.

  PMID: 25678490 BACKGROUND

• 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.

  PMID: 33839262 BACKGROUND

• 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.

  PMID: 21149493 BACKGROUND

• 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.

  PMID: 21976634 BACKGROUND

• 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.

  PMID: 23405207 BACKGROUND

• 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.

  PMID: 33739462 BACKGROUND

• 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.

  PMID: 32749512 BACKGROUND

• 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.

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  PMID: 33538338 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Margins of Excision; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Andrew C Gordon, MD, PhD

CONTACT

(561)703-0134; andrew.gordon@nm.org

Cameron Khakpour, BA

CONTACT

312-926-5509; cameron.khakpour@northwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: We hypothesize that an optimal ablative dose exists between 200-500 Gy, with increasing ablation rates as dose increases, and that the threshold dose to achieve ablation differs between cirrhotic and non-cirrhotic livers. This hypothesis will be tested using voxel-based Y90 PET dosimetry and hepatobiliary MRI to assess dose-response relationships in both structural and functional imaging endpoints. Non-cirrhotic patients will begin at a dose of 200 Gy, while 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.

Study Record Dates

• First Submitted: May 7, 2026
• First Posted: May 14, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): May 1, 2029
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)