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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the treatment AGuIX nanoparticles combined with stereotactic radiation for brain metastases?

Research shows that AGuIX nanoparticles, when used with radiation therapy, can increase tumor cell death and improve survival in animal models with brain metastases. Additionally, in early human trials, these nanoparticles have been shown to accumulate in brain tumors and enhance the effectiveness of radiotherapy. ^{1 2 3 4 5}

Is the combination of AGuIX nanoparticles and stereotactic radiation safe for treating brain metastases?

AGuIX nanoparticles have shown a favorable safety profile in animal studies, with no evidence of toxicity in rodents and monkeys. Early human trials have also indicated a good safety profile when used with radiotherapy for brain metastases. ^{1 3 4 5 6}

How is the AGuIX nanoparticles treatment different from other treatments for brain metastases?

The AGuIX nanoparticles treatment is unique because it combines a gadolinium-based nanoparticle with stereotactic radiation, enhancing the effectiveness of radiation therapy by making cancer cells more sensitive to it. This approach also allows for MRI-guided imaging to precisely target tumors, and the nanoparticles can remain in tumor cells for extended periods, potentially reducing the need for multiple administrations. ^{1 2 3 4 6}

Research Team

Ayal Aizer, MD, MPH

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

References

1. Ireland 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). [2021]

2. England pubmed.ncbi.nlm.nih.gov

MRI-guided clinical 6-MV radiosensitization of glioma using a unique gadolinium-based nanoparticles injection. [2017]

3. England pubmed.ncbi.nlm.nih.gov

Treatment of multiple brain metastases using gadolinium nanoparticles and radiotherapy: NANO-RAD, a phase I study protocol. [2020]

4. Australia pubmed.ncbi.nlm.nih.gov

Gadolinium-Based Nanoparticles and Radiation Therapy for Multiple Brain Melanoma Metastases: Proof of Concept before Phase I Trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Targeting brain metastases with ultrasmall theranostic nanoparticles, a first-in-human trial from an MRI perspective. [2022]

6. England pubmed.ncbi.nlm.nih.gov

AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine. [2021]