Clinical trial NCT04899908: Stereotactic Brain-directed Radiation With or Without Aguix Gadolinium-Based Nanoparticles in Brain Metastases
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Brain Cancer
Brain Metastases
Melanoma
Lung Cancer
Breast Cancer
HER2-positive Breast Cancer
Colorectal Cancer
Gastrointestinal Cancer
SRS
SRT
Whole Brain Radiation
Stereotactic Radiation
AGuIX
Nanoparticle
Cystic
Brain Tumor
Keywords: Brain Cancer
Brain Metastases
Melanoma
Lung Cancer
Breast Cancer
HER2-positive Breast Cancer
Colorectal Cancer
Gastrointestinal Cancer
SRS
SRT
Whole brain radiation
Stereotactic Radiation
AGuIX
Nanoparticle
Cystic
Brain Tumor
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: NH TherAguix SAS
First posted: 2021-05-25
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Local Recurrence
timeFrame: From enrollment to 6 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Time from enrollment to 12 months
measure: Progression-Free Survival (PFS)
timeFrame: Time from enrollment to 12 months
measure: Time to Progression (TTP)
timeFrame: Time from enrollment to 12 months
measure: Death due to neurologic causes
timeFrame: From enrollment to 12 months
measure: Performance status
timeFrame: From enrollment to 12 months
measure: Ability to complete activities of daily living
timeFrame: From enrollment to 12 months
measure: Incidence and time to detection of new brain metastases
timeFrame: From enrollment to 12 months
measure: Incidence and time to detection of radiation necrosis
timeFrame: From enrollment to 12 months
measure: Incidence and time to detection of leptomeningeal disease
timeFrame: From enrollment to 12 months
measure: Incidence and time to detection of progressive intracranial disease
timeFrame: From enrollment to 12 months
measure: Incidence and time to detection of salvage craniotomy
timeFrame: From enrollment to 12 months
measure: Incidence and time to additional radiotherapeutic treatments
timeFrame: From enrollment to 12 months
measure: Incidence and time to the development of seizures
timeFrame: From enrollment to 12 months
measure: Steroid use
timeFrame: From enrollment to 12 months
measure: Local recurrence at one year in metastases treated radiotherapeutically
timeFrame: From enrollment to 12 months
measure: Neurocognitive function: verbal learning and memory
timeFrame: From enrollment to 12 months
measure: Neurocognitive function: visual attention and task switching
timeFrame: From enrollment to 12 months
measure: Neurocognitive function: verbal fluency
timeFrame: From enrollment to 12 months
measure: Neurocognitive function: cognitive impairment
timeFrame: From enrollment to 12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Ayal Aizer, MD, MHS
role: PRINCIPAL_INVESTIGATOR
References: