Stereotactic Brain-directed Radiation With or Without Aguix Gadolinium-Based Nanoparticles in Brain Metastases
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
1 other identifier
interventional
134
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2021
Longer than P75 for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 30, 2021
CompletedFirst Posted
Study publicly available on registry
May 25, 2021
CompletedStudy Start
First participant enrolled
September 15, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 1, 2029
March 19, 2026
March 1, 2026
6.5 years
April 30, 2021
March 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Local Recurrence
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 Outcomes (19)
Overall Survival (OS)
Time from enrollment to 12 months
Progression-Free Survival (PFS)
Time from enrollment to 12 months
Time to Progression (TTP)
Time from enrollment to 12 months
Death due to neurologic causes
From enrollment to 12 months
Performance status
From enrollment to 12 months
- +14 more secondary outcomes
Study Arms (2)
Stereotactic Radiation plus AGuIX gadolinium-based nanoparticles
EXPERIMENTALRandomly 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.
Stereotactic Radiation plus placebo
EXPERIMENTALRandomly 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.
Interventions
Focused radiation beams to treat tumors
Intravenous injection
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Brigham and Women's Hospitallead
- TherAguixcollaborator
- Dana-Farber Cancer Institutecollaborator
Study Sites (2)
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Related Publications (1)
Bennett S, Verry C, Kaza E, Miao X, Dufort S, Boux F, Cremillieux Y, de Beaumont O, Le Duc G, Berbeco R, Sudhyadhom A. Quantifying gadolinium-based nanoparticle uptake distributions in brain metastases via magnetic resonance imaging. Sci Rep. 2024 May 25;14(1):11959. doi: 10.1038/s41598-024-62389-1.
PMID: 38796495DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ayal Aizer, MD, MHS
Brigham and Women's Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
April 30, 2021
First Posted
May 25, 2021
Study Start
September 15, 2021
Primary Completion (Estimated)
April 1, 2028
Study Completion (Estimated)
May 1, 2029
Last Updated
March 19, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
- Access Criteria
- Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
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.