AGuIX Nanoparticles + Stereotactic Radiation for Brain Metastases

Recruiting at 1 trial location

Overseen By Ivy Ricca, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Disqualifiers: Leptomeningeal disease, Pregnancy, Breastfeeding, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 1-2 weeks

134 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether AGuIX nanoparticles (gadolinium-based nanoparticles) can enhance the effectiveness of radiation therapy for individuals with brain metastases, which are cancer cells that have spread to the brain. The goal is to determine if these particles improve cancer control when radiation alone is insufficient. Participants will receive either the nanoparticles with their radiation or a placebo to compare effects. The trial seeks individuals whose cancer has spread to the brain and includes conditions like melanoma or HER2-positive breast cancer that do not respond well to other treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AGuIX gadolinium-based nanoparticles are generally safe. In a previous study, these nanoparticles were used with whole-brain radiation therapy, and the results indicated that the treatment was well-tolerated, with few serious side effects.

These tiny particles help direct radiation to tumors and have been studied in various contexts. Even when combined with radiation therapy, which can be taxing on the body, they have not caused major problems, suggesting they are reasonably safe for humans.

For those considering joining the trial, existing data suggests that the nanoparticles are generally safe and may enhance the effectiveness of radiation treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AGuIX gadolinium-based nanoparticles because they represent a novel approach to treating brain metastases. Unlike standard treatments that primarily focus on radiation alone, AGuIX nanoparticles enhance the effects of stereotactic radiation by targeting tumor cells more precisely. This means the nanoparticles can potentially increase the effectiveness of radiation therapy, offering a more targeted attack on cancer cells while sparing healthy tissue. Additionally, gadolinium-based agents are known for their imaging properties, which could improve how doctors monitor and adjust treatment in real time. This combination of enhanced precision and imaging capability is what sets AGuIX apart from typical radiation treatments.

What evidence suggests that AGuIX gadolinium-based nanoparticles could be an effective treatment for brain metastases?

Research has shown that AGuIX gadolinium-based nanoparticles can enhance the effectiveness of radiation therapy for brain metastases by making cancer cells more sensitive to radiation. In this trial, one group of participants will receive Stereotactic Radiation plus AGuIX gadolinium-based nanoparticles. Studies indicate that AGuIX can accumulate in brain tumors, allowing for more precise targeting of radiation. Early research provides evidence that using AGuIX with radiation can improve tumor control. This method could potentially enhance radiation therapy for difficult-to-treat brain metastases. ^{1 2 3 4 5}

Who Is on the Research Team?

Ayal Aizer, MD, MPH

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults with brain metastases from solid tumors like lung, breast, or gastrointestinal cancer. They must have a Karnofsky performance status of at least 70 and a lesion ≥2cm. Patients should not be pregnant or breastfeeding, able to undergo MRI and gadolinium use, and expected to live at least 3 more months.

Inclusion Criteria

My melanoma has spread to my brain and is growing despite having immunotherapy.

Your kidneys are working well, filtering at a rate of at least 60 mL/min/1.73m2.

I am able to care for myself but cannot do normal activities or work.

Exclusion Criteria

Breastfeeding women

I have brain metastases near critical areas and they've been heavily treated with radiation.

Pregnant women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive stereotactic radiation with or without AGuIX gadolinium-based nanoparticles

1-2 weeks

3-6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• AGuIX gadolinium-based nanoparticles

Trial Overview The study tests if AGuIX nanoparticles can make stereotactic radiation more effective in treating brain metastases that are hard to control with radiation alone. Participants will either receive the nanoparticles with radiation or a placebo with radiation.

How Is the Trial Designed?

Group I: Stereotactic Radiation plus placebo Experimental Treatment 2 Interventions

Randomly 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.

Group II: Stereotactic Radiation plus AGuIX gadolinium-based nanoparticles Experimental Treatment 2 Interventions

Randomly 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.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

NH TherAguix SAS

Collaborator

Trials

4

Recruited

350+

Published Research Related to This Trial

AGuIX® nanoparticles, which are very small and made from a polysiloxane matrix with gadolinium, have shown no toxicity in animal studies, indicating a good safety profile for potential clinical use.

These nanoparticles enhance the effectiveness of radiotherapy by significantly increasing radiosensitivity in various cancer types, including brain and lung cancers, and have successfully progressed to early human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine. Lux, F., Tran, VL., Thomas, E., et al.[2021]

The phase I NANO-RAD trial demonstrated that the gadolinium-based nanoparticle AGuIX can be safely administered in escalating doses up to 100 mg/kg without dose-limiting toxic effects in patients with multiple brain metastases.

AGuIX showed effective targeting and retention in brain metastases, leading to clinical benefits in 13 out of 14 evaluable patients, including tumor stabilization or reduction, suggesting a potential radiosensitizing effect when combined with whole brain radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theranostic AGuIX nanoparticles as radiosensitizer: A phase I, dose-escalation study in patients with multiple brain metastases (NANO-RAD trial). Verry, C., Dufort, S., Villa, J., et al.[2021]

In a phase 1 clinical trial involving 15 patients with various types of brain metastases, Gd-based AGuIX nanoparticles were successfully administered intravenously, showing significant accumulation and enhanced MRI contrast in all cases, comparable to standard contrast agents.

The nanoparticles not only improved imaging but also have radiosensitizing properties, allowing for subsequent radiotherapy sessions, and this promising approach is being further tested in a larger phase 2 trial with 100 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting brain metastases with ultrasmall theranostic nanoparticles, a first-in-human trial from an MRI perspective. Verry, C., Dufort, S., Lemasson, B., et al.[2022]

The NANO-RAD study is a phase I clinical trial investigating the safety and tolerability of AGuIX nanoparticles combined with whole brain radiotherapy (WBRT) in patients with multiple brain metastases, aiming to determine the maximum-tolerated dose.

This study will assess the pharmacokinetics and distribution of AGuIX in brain metastases and surrounding tissue, with a total of 15-18 patients planned for recruitment, highlighting its potential as a radiosensitizer in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of multiple brain metastases using gadolinium nanoparticles and radiotherapy: NANO-RAD, a phase I study protocol. Verry, C., Sancey, L., Dufort, S., et al.[2020]

AGuIX nanoparticles (NPs) demonstrated a strong safety profile in rodents, allowing for effective tumor imaging via MRI for up to 24 hours after a single intravenous dose.

When combined with standard 6-MV radiotherapy, AGuIX NPs not only improved tumor visualization but also contributed to a reduction in tumor volume, highlighting their potential as a theranostic tool for brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI-guided clinical 6-MV radiosensitization of glioma using a unique gadolinium-based nanoparticles injection. Verry, C., Dufort, S., Barbier, EL., et al.[2017]

AGuIX® nanoparticles containing gadolinium can enhance the effectiveness of radiation therapy by increasing tumor cell death and extending the lifespan of animals with brain melanoma metastases.

These nanoparticles can remain in tumor cells for over 24 hours after a single injection, suggesting that they may allow for multiple radiation treatments without the need for repeated doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gadolinium-Based Nanoparticles and Radiation Therapy for Multiple Brain Melanoma Metastases: Proof of Concept before Phase I Trial. Kotb, S., Detappe, A., Lux, F., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04899908

Study Details | NCT04899908 | Stereotactic Brain-directed ... AGuIX gadolinium-based nanoparticles have been tested in other studies for safety and efficacy in patients with brain metastases who are also receiving ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11342789/

NANO-GBM trial of AGuIX nanoparticles with radiotherapy ... AGuIX nanoparticles have shown promise as effective radiosensitizers and contrast agents [6]. Preclinical studies on orthotopic tumor models, ...

3. nature.com nature.com/articles/s41598-024-62389-1

Quantifying gadolinium-based nanoparticle uptake ... This research demonstrates AGuIX's ability to accumulate in brain metastases, with quantifiable uptake via mapping.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6435081/

AGuIX® from bench to bedside—Transfer of an ultrasmall ... AGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates. This nanoparticle has been recently accepted in clinical trials in ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04094077

NCT04094077 | Evaluating AGuIX® Nanoparticles in ... This study evaluates the clinical impact of AGuIX® nanoparticles in combination with Fractionated Stereotactic Radiation in oligo brain metastases.