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NANORAD2: Radiotherapy of Multiple Brain Metastases Using AGuIX®

Sponsor
University Hospital, Grenoble (Other)
Overall Status
Recruiting
CT.gov ID
NCT03818386
Collaborator
NH TherAguix SAS (Other)
100
Enrollment
15
Locations
2
Arms
47.2
Anticipated Duration (Months)
6.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Prospective Randomized Open Blinded Endpoint phase II clinical trial.Prospective Randomized Open Blinded Endpoint phase II clinical trial.
Masking:
Single (Outcomes Assessor)
Masking Description:
The main endpoint will be evaluated by a blinded endpoint committee.
Primary Purpose:
Treatment
Official Title:
Radiotherapy of Multiple Brain Metastases Using AGuIX® Gadolinium-chelated Polysiloxane Based Nanoparticles: a Prospective Randomized Phase II Clinical Trial.
Actual Study Start Date :
Mar 26, 2019
Anticipated Primary Completion Date :
Mar 1, 2023
Anticipated Study Completion Date :
Mar 1, 2023

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Best objective intracranial response rate - intent-to-treat [at 6 weeks]

      Evaluation of brain metastases response, according to RECIST v1.1 criteria (or modified RECIST) by MRI, with MRI centralized reading

    2. Best objective intracranial response rate - intent-to-treat [at 3 months]

      Evaluation of brain metastases response, according to RECIST v1.1 criteria (or modified RECIST) by MRI, with MRI centralized reading

    Secondary Outcome Measures

    1. Evaluation of the quality of life [at D0, 6 weeks, 3, 6, 9, 12 months]

      Quality of life test score EORTC QLQ C30

    2. Evaluation of the quality of life [at day 0, 6 weeks, 3, 6, 9, 12 months]

      Quality of life test score EORTC QLQ BN20

    3. Neurocognitive evaluation [at Day 0, 6 weeks, 3, 6, 9, 12 months]

      Neurocognitive test (MoCA)

    4. Best objective intracranial response rate - per-protocol [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

    5. Evaluation of the intracranial response rate [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

    6. Evaluation of individual metastasis response [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

    7. Intracranial progression-free survival [at 12 months]

      Evaluation of the time between the start of the treatment and the occurence of intracranial progression or neuriologic death

    8. Intracranial progression-free survival, brain survival [at 12 months]

      Death related to brain metastases progression

    9. Overall survival [at 12 months]

      Death

    10. Change in steroid dependence [at 6 weeks and 3, 6, 9 and 12 months]

      Reporting of daily steroid dose

    11. Incidence of adverse events [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)

    12. MRI study of the distribution of the product in brain metastases [Day 0]

      MRI evaluation of contrast enhancement at D0 after AGuIX® injection

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Institut Régional du Cancer Montpellier Occitanie France 34298
    2 Institut Claudius Regaud Institut Universitaire du Cancer Toulouse Oncopole Radiothérapie Toulouse Occitanie France 31059
    3 Centre Leon Berard Lyon Lyon Rhones Alpes France 69373
    4 Centre Hospitalier Annecy Genevois Annecy Rhones-Alpes France 74374
    5 Centre hospitalier universitaire Grenoble-Alpes Grenoble Rhones-Alpes France 38700
    6 CRLCC - Institut Bergonié Bordeaux France 33000
    7 Crlcc Francois Baclesse Caen France 14000
    8 Centre Georges François Leclerc Dijon France 21079
    9 Centre OSCAR LAMBRET Lille France 59000
    10 Hospices Civils de Lyon-Hôpital Lyon Sud Lyon France 69495
    11 Hôpital Européen Georges Pompidou Paris France 75015
    12 La Pitié Salpêtrière - Charles Foix Paris France 75651
    13 Institut Curie Saint Cloud Saint-Cloud France 92210
    14 Crlcc Paul Strauss Strasbourg France 67085
    15 Institut de Cancérologie de Lorraine ALEXIS VAUTRIN Vandœuvre-lès-Nancy France 54519

    Sponsors and Collaborators

    • University Hospital, Grenoble
    • NH TherAguix SAS

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    University Hospital, Grenoble
    ClinicalTrials.gov Identifier:
    NCT03818386
    Other Study ID Numbers:
    • 38RC18.085
    First Posted:
    Jan 28, 2019
    Last Update Posted:
    Jul 14, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by University Hospital, Grenoble
    gadolinium nanoparticles
    AGuIX
    Additional relevant MeSH terms:
    Neoplasm Metastasis
    Brain Neoplasms

    Study Results

    No Results Posted as of Jul 14, 2022