Stereotactic Brain-directed Radiation With or Without Aguix Gadolinium-Based Nanoparticles in Brain Metastases

March 17, 2026 updated by: Ayal A. Aizer, MD, Brigham and Women's Hospital

A Double-blind, Phase II Randomized Study of Brain-directed Stereotactic Radiation With or Without AGuIX Gadolinium-based Nanoparticles in the Management of Brain Metastases at Higher Risk of Local Recurrence With Radiation Alone

The purpose of this study is to determine whether AGuIX (Activation and Guidance of Irradiation by X-ray) gadolinium-based nanoparticles make radiation work more effectively in the treatment of patients with brain metastases that are more difficult to control with stereotactic radiation alone.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This research study is a double-blind, randomized phase II clinical trial of brain-directed stereotactic radiation with or without AGuIX (Activation and Guidance of Irradiation by X-ray) gadolinium-based nanoparticles in the management of brain metastases at higher-risk of local recurrence with radiation alone.

The study agent (AGuIX gadolinium-based nanoparticles) has two main parts. The first is gadolinium, also known as "contrast," which is typically injected into a vein during a MRI scan. The second part is a nanoparticle (linked to the gadolinium) that may make focused radiation work more effectively. The AGuIX gadolinium-based nanoparticles are deposited within the brain metastases via the bloodstream and then the brain metastases are radiated.

The U.S. Food and Drug Administration (FDA) has not approved AGuIX gadolinium-based nanoparticles as a treatment for any disease. AGuIX gadolinium-based nanoparticles have been tested in other studies for safety and efficacy in patients with brain metastases who are also receiving radiation.

This study seeks to determine whether AGuIX gadolinium-based nanoparticles improve outcomes relative to placebo.Participants will be "randomized" into one of the study groups:

  • Group A: Radiation plus AGuIX gadolinium-based nanoparticles
  • Group B: Radiation plus placebo

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

NH TherAguix, the manufacturer of the AGuIX gadolinium-based nanoparticles, is supporting this research study by providing the AGuIX gadolinium-based nanoparticles that will be evaluated in this study.

NH TherAguix is also covering the cost of the study.

It is expected that about 134 people will take part in this research study.

Study Type

Interventional

Enrollment (Estimated)

134

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 Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants must have a biopsy proven solid malignancy and at least one intracranial measurable lesion spanning ≥5mm in maximal unidimensional size and radiographically consistent with or pathologically proven to be a brain metastasis AND meet one of the following additional criteria regarding the primary site or nature of the intracranial disease:

    • Melanoma with intracranial growth consistent with tumor progression despite immunotherapy
    • Gastrointestinal primary
    • HER2 positive breast cancer (subtype assessed using most representative tissue available in opinion of enrolling clinician and/or study PI)
    • Cystic metastases
    • Metastases ≥2cm in maximal unidimensional size
    • Locally recurrent metastases after prior stereotactic radiation
    • Locally recurrent metastases after prior whole brain radiation *Patients with metastases from melanoma, GI primaries, or HER2+ breast cancer, as well as those with cystic metastases or metastases ≥2cm in maximal unidimensional size, who have local recurrences after prior brain-directed radiation can only be treated in the strata permitting prior radiation (last two strata above)
  • Age ≥18 years at diagnosis of brain metastases
  • Estimated glomerular filtration rate of ≥ 60 mL/min/1.73m2
  • Karnofsky performance status of at least 70 (i.e. at minimum, "cares for self" but "unable to carry on normal activity or do active work")
  • Estimated survival based on extracranial disease of at least 3 months in the opinion of the enrolling clinician and/or study PI
  • Ability to understand and the willingness to sign a written informed consent document
  • The effects of AGuIX on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of the therapeutic component of study participation

Exclusion Criteria:

  • Participants who cannot undergo a brain MRI
  • Participants who cannot receive gadolinium
  • Participants with widespread, definitive leptomeningeal disease
  • Patients requiring radiation to either >10 targets (if naïve to whole brain radiation) or >20 targets (if whole brain radiation has been given previously) per the discretion of the treating clinician and/or study PI
  • Pregnant women are excluded from this study because of the potential deleterious effects of gadolinium on the developing fetus. Because there is an unknown but potential risk for adverse events in nursing infants, women who are breastfeeding are not eligible for this study
  • In cohorts who have received prior brain-directed radiation, patients are not eligible for this study if they have active (at the time of protocol screening) brain metastases that require radiation that are in or within 1.0cm of the brainstem, eyes, optic nerves, or optic chiasm if the juxtaposed organ at risk (i.e. brainstem, eyes, optic nerves, or optic chiasm) has previously received either >6.0 Gy in a single fraction or, if prior radiation was fractionated, a cumulative dose in 2.0 Gy equivalents, using an alpha/beta ratio of 2, of >40.0 Gy. In addition, all patients who have had prior brain-directed radiation, regardless of technique/dose/fractionation, are not eligible for the study until written approval is provided by the study/site PI

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Stereotactic Radiation plus AGuIX gadolinium-based nanoparticles

Randomly assigned participants will receive:

  • AGuIX gadolinium-based nanoparticles 3-5 days before radiation is initiated

  • AGuIX gadolinium-based up to 2x during radiation, depending on standard of care radiation treatment.

    • If standard of care radiation treatment involves only one day of radiation, participant will receive AGuIX gadolinium-based nanoparticles on the day of radiation.
    • If standard of care radiation treatment involves 5 or 6 days of radiation, participant will receive AGuIX gadolinium-based nanoparticles two-times (2x) in total, on the first and third day of radiation.
Radiation: Stereotactic Radiation
Focused radiation beams to treat tumors
Other Names:
  • Stereotactic Radiotherapy
Drug: AGuIX gadolinium-based nanoparticles
Intravenous injection
Experimental: Stereotactic Radiation plus placebo

Randomly assigned participants will receive:

  • Placebo 3-5 days before radiation is initiated

  • Placebo up to 2x during radiation, depending on standard of care radiation treatment.

    • If standard of care radiation treatment involves only one day of radiation participant will receive Placebo on the day of radiation.
    • If standard of care radiation treatment involves 5 or 6 days of radiation participant will receive Placebo two-times (2x) in total, on the first and third day of radiation.
Other: Placebo
Intravenous infusion
Other Names:
  • Saline
Radiation: Stereotactic Radiation
Focused radiation beams to treat tumors
Other Names:
  • Stereotactic Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Local Recurrence
Time Frame: From enrollment to 6 months
Assessed with Response Assessment in Neuro-Oncology (RANO) - Brain Metastasis Guidelines Time to local failure on a per metastasis basis will be performed using the log-rank test.
From enrollment to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Time from enrollment to 12 months
Assessed with log-rank test
Time from enrollment to 12 months
Progression-Free Survival (PFS)
Time Frame: Time from enrollment to 12 months
Assessed with log-rank test
Time from enrollment to 12 months
Time to Progression (TTP)
Time Frame: Time from enrollment to 12 months
Assessed with log-rank test
Time from enrollment to 12 months
Death due to neurologic causes
Time Frame: From enrollment to 12 months
Assessed with Gray's test
From enrollment to 12 months
Performance status
Time Frame: From enrollment to 12 months
Karnofsky performance status, assessed longitudinally (longitudinal regression)
From enrollment to 12 months
Ability to complete activities of daily living
Time Frame: From enrollment to 12 months
Questionnaire - EQ-5D, assessed longitudinally (longitudinal regression)
From enrollment to 12 months
Incidence and time to detection of new brain metastases
Time Frame: From enrollment to 12 months
Assessed with log-rank test
From enrollment to 12 months
Incidence and time to detection of radiation necrosis
Time Frame: From enrollment to 12 months
Assessed with log-rank test
From enrollment to 12 months
Incidence and time to detection of leptomeningeal disease
Time Frame: From enrollment to 12 months
Assessed with log-rank test
From enrollment to 12 months
Incidence and time to detection of progressive intracranial disease
Time Frame: From enrollment to 12 months
Assessed with log-rank test
From enrollment to 12 months
Incidence and time to detection of salvage craniotomy
Time Frame: From enrollment to 12 months
Assessed with log-rank test
From enrollment to 12 months
Incidence and time to additional radiotherapeutic treatments
Time Frame: From enrollment to 12 months
Assessed with log-rank test
From enrollment to 12 months
Incidence and time to the development of seizures
Time Frame: From enrollment to 12 months
Assessed with log-rank test
From enrollment to 12 months
Steroid use
Time Frame: From enrollment to 12 months
Assessed longitudinally (longitudinal regression)
From enrollment to 12 months
Local recurrence at one year in metastases treated radiotherapeutically
Time Frame: From enrollment to 12 months
Assessed using RECIST (response evaluation criteria in solid tumors) criteria
From enrollment to 12 months
Neurocognitive function: verbal learning and memory
Time Frame: From enrollment to 12 months
Hopkins Verbal Learning Test - Revised (HVLT-R)
From enrollment to 12 months
Neurocognitive function: visual attention and task switching
Time Frame: From enrollment to 12 months
Trail Making Test Part A and B (TMT)
From enrollment to 12 months
Neurocognitive function: verbal fluency
Time Frame: From enrollment to 12 months
Controlled Word Association Test (COWAT)
From enrollment to 12 months
Neurocognitive function: cognitive impairment
Time Frame: From enrollment to 12 months
Mini Mental Status Examination (MMSE)
From enrollment to 12 months

Collaborators and Investigators

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

Sponsor

Brigham and Women's Hospital

Collaborators

Dana-Farber Cancer Institute
TherAguix

Investigators

  • Principal Investigator: Ayal Aizer, MD, MHS, Brigham and Women's Hospital

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 (Actual)

September 15, 2021

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

April 30, 2021

First Submitted That Met QC Criteria

May 19, 2021

First Posted (Actual)

May 25, 2021

Study Record Updates

Last Update Posted (Actual)

March 19, 2026

Last Update Submitted That Met QC Criteria

March 17, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20-240

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

IPD Sharing Time Frame

Data can be shared no earlier than 1 year following the date of publication

IPD Sharing Access Criteria

Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

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.

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