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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
134
Focused radiation beams to treat tumors
Intravenous injection
Intravenous infusion
Brigham and Women's Hospital
Boston, Massachusetts, United States
RECRUITINGDana Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGLocal 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.
Time frame: From enrollment to 6 months
Overall Survival (OS)
Assessed with log-rank test
Time frame: Time from enrollment to 12 months
Progression-Free Survival (PFS)
Assessed with log-rank test
Time frame: Time from enrollment to 12 months
Time to Progression (TTP)
Assessed with log-rank test
Time frame: Time from enrollment to 12 months
Death due to neurologic causes
Assessed with Gray's test
Time frame: From enrollment to 12 months
Performance status
Karnofsky performance status, assessed longitudinally (longitudinal regression)
Time frame: From enrollment to 12 months
Ability to complete activities of daily living
Questionnaire - EQ-5D, assessed longitudinally (longitudinal regression)
Time frame: From enrollment to 12 months
Incidence and time to detection of new brain metastases
Assessed with log-rank test
Time frame: From enrollment to 12 months
Incidence and time to detection of radiation necrosis
Assessed with log-rank test
Time frame: From enrollment to 12 months
Incidence and time to detection of leptomeningeal disease
Assessed with log-rank test
Time frame: From enrollment to 12 months
Incidence and time to detection of progressive intracranial disease
Assessed with log-rank test
Time frame: From enrollment to 12 months
Incidence and time to detection of salvage craniotomy
Assessed with log-rank test
Time frame: From enrollment to 12 months
Incidence and time to additional radiotherapeutic treatments
Assessed with log-rank test
Time frame: From enrollment to 12 months
Incidence and time to the development of seizures
Assessed with log-rank test
Time frame: From enrollment to 12 months
Steroid use
Assessed longitudinally (longitudinal regression)
Time frame: From enrollment to 12 months
Local recurrence at one year in metastases treated radiotherapeutically
Assessed using RECIST (response evaluation criteria in solid tumors) criteria
Time frame: From enrollment to 12 months
Neurocognitive function: verbal learning and memory
Hopkins Verbal Learning Test - Revised (HVLT-R)
Time frame: From enrollment to 12 months
Neurocognitive function: visual attention and task switching
Trail Making Test Part A and B (TMT)
Time frame: From enrollment to 12 months
Neurocognitive function: verbal fluency
Controlled Word Association Test (COWAT)
Time frame: From enrollment to 12 months
Neurocognitive function: cognitive impairment
Mini Mental Status Examination (MMSE)
Time frame: From enrollment to 12 months
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