Defining the Ablative Dose for Y-90 TARE (MARGIN)

May 7, 2026 updated by: 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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Andrew C Gordon, MD, PhD
        • Sub-Investigator:
          • Robert J Lewandowski, MD, FSIR
        • Sub-Investigator:
          • Amir A Borhani, MD
        • Sub-Investigator:
          • Saad E Abu Zahra, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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
Other: 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.
Active Comparator: 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.
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ablative Dose Threshold for Y90 Radiation Segmentectomy
Time Frame: 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
Time Frame: 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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation of Y90 Dose with Imaging Biomarkers
Time Frame: 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
Time Frame: 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
Time Frame: 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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathologic Necrosis in Explanted Tumors
Time Frame: 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
Time Frame: 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

February 1, 2029

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

May 7, 2026

First Submitted That Met QC Criteria

May 7, 2026

First Posted (Actual)

May 14, 2026

Study Record Updates

Last Update Posted (Actual)

May 14, 2026

Last Update Submitted That Met QC Criteria

May 7, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU00224943

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HCC - Hepatocellular Carcinoma

Clinical Trials on Yttrium-90 Radiation Segmentectomy (Y90 RS) using glass microspheres

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Paraguay

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe