Using nanoparticles to enhance radiation treatment for 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

This study is testing if adding special nanoparticles to radiation therapy can help people with brain metastases get better results than radiation alone.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 134 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Dana-Farber Cancer Institute (Academic / other)
• Drugs / interventions: immunotherapy, radiation
• Locations: 2 sites (Boston, Massachusetts and 1 other locations)
• Trial ID: NCT04899908 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of AGuIX gadolinium-based nanoparticles in combination with stereotactic radiation therapy for patients with brain metastases. It is a double-blind, randomized phase II trial where participants are assigned to receive either radiation with AGuIX nanoparticles or radiation with a placebo. The nanoparticles are designed to improve the efficacy of radiation treatment by being deposited within the brain metastases via the bloodstream. The study aims to determine if this combination leads to better outcomes compared to radiation alone.

Who should consider this trial

Good fit: Ideal candidates include patients with biopsy-proven solid malignancies and measurable brain metastases, particularly those with melanoma, HER2 positive breast cancer, or gastrointestinal cancers.

Not a fit: Patients with brain metastases that are not measurable or those who do not have the specified types of cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with difficult-to-treat brain metastases.

How similar studies have performed: While the use of nanoparticles in radiation therapy is an emerging field, previous studies have shown promise in enhancing treatment efficacy, making this approach both innovative and potentially impactful.

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

Where this trial is running

Boston, Massachusetts and 1 other locations

• Brigham and Women's Hospital — Boston, Massachusetts, United States (Recruiting)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Ayal Aizer, MD, MHS — Brigham and Women's Hospital
• Study coordinator: Ayal Aizer, MD, MHS

Conditions Brain Cancer; Brain Metastases; Melanoma; Lung Cancer; Breast Cancer; HER2-positive Breast Cancer; Colorectal Cancer; Gastrointestinal Cancer