Radiotherapy of Multiple Brain Metastases Using AGuIX® (NANORAD2)

Grenoble Alpes University Hospital Center (CHU)

Status and phase: Active, not recruiting; Phase 2

Conditions: Brain Metastases, Adult; Radiotherapy

Treatments: Radiation: Whole Brain Radiation Therapy; Drug: AGuIX®

Study type: Interventional

Funder types: Other

Identifiers

NCT03818386

38RC18.085

Details and patient eligibility

About

This is a Prospective Randomized Open Blinded Endpoint phase II clinical trial. The study will be adaptive: an interim analysis is planned after enrolment of 20 patients in each arm of treatment (WBRT and AGuIX® + WBRT), to select and continue the study with group(s) that present the best response rate to the experimental treatment (AGuIX® + WBRT).

The main endpoint will be evaluated by a blinded endpoint committee.

Full description

The occurrence of brain metastases is a common event in the history of cancer and negatively affects the life expectancy of patients. Their incidence varies between 15 and 50% according to the histologic types. Surgery, stereotactic radiosurgery, radiotherapy and chemotherapy are the main treatments currently proposed.

For patients with multiple brain metastases, whole brain radiation therapy (WBRT) remains the standard of care. However, the median overall survival is less than 6 months and new approaches need to be developed to improve treatment of these patients.

In this context, the weak control of the disease comes from three main factors: the multiplicity of the brain lesions, the radioresistance of certain histologies and the poor distribution of cytotoxic agents in brain metastases.

The use of radiosensitizing agents is here of great interest. The radiosensitizing agent chosen in this study is AGuIX®. It is a Gadolinium-chelated polysiloxane based nanoparticle developed by NH TherAguix company for its theranostic properties (radiosensitization and diagnosis by multimodal imaging). Preclinical studies have demonstrated the radiosensitizing effect of AGuIX® in vivo in 8 tumor models xenografted in rodents, and particularly in brain tumors.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with brain metastases, from a histologically confirmed solid tumor, eligible for WBRT

• At least 18 years old

• Signed informed consent after informing the patient

• ECOG (Eastern Cooperative Oncology Group) performance status 0-2

• Extracranial disease:

  • Complete or partial response or stability under systemic treatment
  • No extracranial disease
  • Or first line of treatment

• Life expectancy greater than 6 weeks

• Effective contraceptive method for all patient of childbearing potential

• Affiliated to a social security regimen

Exclusion criteria

• Leptomeningeal metastasis
• Evidence of metastasis with recent large hemorrhage
• Progressive and threatening extracranial disease under systemic treatment
• Previous cranial irradiation (except stereotactic irradiation)
• Known contra-indication, sensitivity or allergy to gadolinium
• Known contra-indication for Magnetic Resonance Imaging
• Renal insufficiency (glomerular filtration rate ≤ 50 mL/min/1.73m²)
• Pregnancy or breastfeeding
• Subject under administrative or judicial control

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 2 patient groups

AGuIX® + Whole Brain Radiation Therapy

Experimental group

Description:

Intervention: Drug: AGuIX® + WBRT Other Names: Gadolinium-chelated polysiloxane based nanoparticles 3 intravenous injections at 100mg/kg * D0: AGuIX® injection followed by MRI (within 7 days before commencement of WBRT) * Fr1: AGuIX® injection before the first radiation session * Fr6: AGuIX® injection before the sixth radiation session 30 Gy in 10 fractions of 3 Gy over 2-3 weeks

Treatment:

Drug: AGuIX®

Radiation: Whole Brain Radiation Therapy

Whole Brain Radiation Therapy

Active Comparator group

Description:

Intervention: Radiation: Whole Brain Radiation Therapy ( WBRT) 30 Gy in 10 fractions of 3 Gy over 2-3 weeks

Treatment:

Radiation: Whole Brain Radiation Therapy