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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04899908
Other study ID # 20-240
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date September 15, 2021
Est. completion date February 2026

Study information

Verified date September 2023
Source Dana-Farber Cancer Institute
Contact Ayal Aizer, MD, MHS
Phone (617) 732-7560
Email aaaizer@partners.org
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 134
Est. completion date February 2026
Est. primary completion date February 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

Radiation:
Stereotactic Radiation
Focused radiation beams to treat tumors
Drug:
AGuIX gadolinium-based nanoparticles
Intravenous injection
Other:
Placebo
Intravenous infusion

Locations

Country Name City State
United States Brigham and Women's Hospital Boston Massachusetts
United States Dana Farber Cancer Institute Boston Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
Dana-Farber Cancer Institute NH TherAguix SAS

Country where clinical trial is conducted

United States, 

Outcome

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