Radiotherapy of Multiple Brain Metastases Using AGuIX® (NANORAD2)

June 13, 2024 updated by: University Hospital, Grenoble

Radiotherapy of Multiple Brain Metastases Using AGuIX® Gadolinium-chelated Polysiloxane Based Nanoparticles: a Prospective Randomized Phase II Clinical Trial.

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bordeaux, France, 33000
        • CRLCC - Institut Bergonié
      • Caen, France, 14000
        • Crlcc Francois Baclesse
      • Dijon, France, 21079
        • Centre Georges François Leclerc
      • Lyon, France, 69495
        • Hospices Civils de Lyon-Hopital Lyon Sud
      • Paris, France, 75015
        • Hôpital Européen Georges Pompidou
      • Paris, France, 75651
        • La Pitié Salpêtrière - Charles Foix
      • Saint-Cloud, France, 92210
        • Institut Curie Saint Cloud
      • Strasbourg, France, 67085
        • Crlcc Paul Strauss
      • Vandœuvre-lès-Nancy, France, 54519
        • Institut de Cancérologie de Lorraine Alexis Vautrin
    • Occitanie
      • Montpellier, Occitanie, France, 34298
        • Institut Régional du Cancer
      • Toulouse, Occitanie, France, 31059
        • Institut Claudius Regaud Institut Universitaire du Cancer Toulouse Oncopole Radiothérapie
    • Rhones Alpes
      • Lyon, Rhones Alpes, France, 69373
        • Centre Léon Berard Lyon
    • Rhones-Alpes
      • Annecy, Rhones-Alpes, France, 74374
        • Centre Hospitalier Annecy Genevois
      • Grenoble, Rhones-Alpes, France, 38700
        • Centre Hospitalier Universitaire Grenoble-Alpes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AGuIX® + Whole Brain Radiation Therapy

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
Drug: AGuIX®

3 intravenous injection 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
Other Names:
  • Gadolinium-chelated polysiloxane based nanoparticles
Radiation: Whole Brain Radiation Therapy
30 Gy in 10 fractions of 3 Gy over 2-3 weeks
Other Names:
  • WBRT
Active Comparator: Whole Brain Radiation Therapy
Intervention: Radiation: Whole Brain Radiation Therapy ( WBRT) 30 Gy in 10 fractions of 3 Gy over 2-3 weeks
Radiation: Whole Brain Radiation Therapy
30 Gy in 10 fractions of 3 Gy over 2-3 weeks
Other Names:
  • WBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best objective intracranial response rate - intent-to-treat
Time Frame: at 6 weeks
Evaluation of brain metastases response, according to RECIST v1.1 criteria (or modified RECIST) by MRI, with MRI centralized reading
at 6 weeks
Best objective intracranial response rate - intent-to-treat
Time Frame: at 3 months
Evaluation of brain metastases response, according to RECIST v1.1 criteria (or modified RECIST) by MRI, with MRI centralized reading
at 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of the quality of life
Time Frame: at D0, 6 weeks, 3, 6, 9, 12 months
Quality of life test score EORTC QLQ C30
at D0, 6 weeks, 3, 6, 9, 12 months
Evaluation of the quality of life
Time Frame: at day 0, 6 weeks, 3, 6, 9, 12 months
Quality of life test score EORTC QLQ BN20
at day 0, 6 weeks, 3, 6, 9, 12 months
Neurocognitive evaluation
Time Frame: at Day 0, 6 weeks, 3, 6, 9, 12 months
Neurocognitive test (MoCA)
at Day 0, 6 weeks, 3, 6, 9, 12 months
Best objective intracranial response rate - per-protocol
Time Frame: at 6 weeks and 3 months
Evaluation of brain metastases response on per-protocol population, according to RECIST v1.1 criteria (or modified RECIST), by MRI with centralized reading
at 6 weeks and 3 months
Evaluation of the intracranial response rate
Time Frame: for 12 months
Evaluation of brain metastases response, according to RANO, to RECIST v1.1 criteria, and as the evolution of the sum of longest diameters (for all metastases with a sum of diameters > 1cm), by MRI, at 6 weeks and 3, 6, 9 and 12 months
for 12 months
Evaluation of individual metastasis response
Time Frame: at 6 weeks and 3, 6, 9 and 12 months
Evaluation of individual brain metastasis response, for all metastases with the sum of diameters > 1cm, by MRI rate
at 6 weeks and 3, 6, 9 and 12 months
Intracranial progression-free survival
Time Frame: at 12 months
Evaluation of the time between the start of the treatment and the occurence of intracranial progression or neuriologic death
at 12 months
Intracranial progression-free survival, brain survival
Time Frame: at 12 months
Death related to brain metastases progression
at 12 months
Overall survival
Time Frame: at 12 months
Death
at 12 months
Change in steroid dependence
Time Frame: at 6 weeks and 3, 6, 9 and 12 months
Reporting of daily steroid dose
at 6 weeks and 3, 6, 9 and 12 months
Incidence of adverse events
Time Frame: at 6 weeks and 3, 6, 9 and 12 months
Reporting of adverse events by type, frequency and severity for both treatments (WBRT and AGuIX® + WBRT)
at 6 weeks and 3, 6, 9 and 12 months
MRI study of the distribution of the product in brain metastases
Time Frame: Day 0
MRI evaluation of contrast enhancement at D0 after AGuIX® injection
Day 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Grenoble

Collaborators

NH TherAguix SAS

Investigators

  • Principal Investigator: Camille VERRY, MD, University Hospital, Grenoble

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 26, 2019

Primary Completion (Estimated)

June 26, 2024

Study Completion (Estimated)

March 26, 2025

Study Registration Dates

First Submitted

December 11, 2018

First Submitted That Met QC Criteria

January 24, 2019

First Posted (Actual)

January 28, 2019

Study Record Updates

Last Update Posted (Actual)

June 14, 2024

Last Update Submitted That Met QC Criteria

June 13, 2024

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38RC18.085

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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