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Radiotherapy of Multiple Brain Metastases Using AGuIX® (NANORAD2)

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ClinicalTrials.gov Identifier: NCT03818386
Recruitment Status : Recruiting
First Posted : January 28, 2019
Last Update Posted : April 5, 2019
Sponsor:
Collaborator:
NH TherAguix SAS
Information provided by (Responsible Party):
University Hospital, Grenoble

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
Brain Metastases, Adult Radiotherapy Drug: AGuIX® Radiation: Whole Brain Radiation Therapy 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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 : March 26, 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2022

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)
  • S1: AGuIX® injection before the first radiation session
  • S6: 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)
  • S1: AGuIX® injection before the first radiation session
  • S6: AGuIX® injection before the sixth radiation session
Other Name: Gadolinium-chelated polysiloxane based nanoparticles

Radiation: Whole Brain Radiation Therapy
30 Gy in 10 fractions of 3 Gy over 2-3 weeks
Other Name: 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 Name: WBRT




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Neurocognitive evaluation [ Time Frame: at Day 0, 6 weeks, 3, 6, 9, 12 months ]
    Neurocognitive test (MoCA)

  4. 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

  5. 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

  6. 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

  7. 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

  8. Intracranial progression-free survival, brain survival [ Time Frame: at 12 months ]
    Death related to brain metastases progression

  9. Overall survival [ Time Frame: at 12 months ]
    Death

  10. Change in steroid dependence [ Time Frame: at 6 weeks and 3, 6, 9 and 12 months ]
    Reporting of daily steroid dose

  11. 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)

  12. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03818386


Contacts
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Contact: Camille VERRY, MD +33 (0)4 76 76 54 35 cverry@chu-grenoble.fr
Contact: Anais ADOLLE +33 (0)4 76 76 68 13 aadolle@chu-grenoble.fr

Locations
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France
Centre hospitalier universitaire Grenoble-Alpes Recruiting
Grenoble, Rhones-Alpes, France, 38700
Contact: Camille VERRY    +33476765435    cverry@chu-grenoble.fr   
Contact: Anaïs ADOLLE    +33476766813    aadolle@chu-grenoble.fr   
CRLCC - Institut Bergonié Not yet recruiting
Bordeau, France, 33000
Principal Investigator: PAUL SARGOS, MD PHD         
Crlcc Francois Baclesse Not yet recruiting
Caen, France, 14000
Principal Investigator: DINU STEFAN, MD         
Centre Antoine Lacassagne Not yet recruiting
Nice, France, 06189
Principal Investigator: JEROME DOYEN, MD         
Hôpital Européen Georges Pompidou Not yet recruiting
Paris, France, 75015
Principal Investigator: PHILIPPE GIRAUD, MD, PHD         
Pitié Salpêtrière - Charles Foix Not yet recruiting
Paris, France, 75651
Principal Investigator: LOIC FEUVERT, MD         
Crlcc Paul Strauss Not yet recruiting
Strasbourg, France, 67085
Principal Investigator: GEORGE NOEL, MD PHD         
Icl Alexis Vautrin Not yet recruiting
Vandœuvre-lès-Nancy, France
Principal Investigator: GUILLAUME VOGIN, MD         
Sponsors and Collaborators
University Hospital, Grenoble
NH TherAguix SAS
Investigators
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Principal Investigator: Camille VERRY, MD University Hospital, Grenoble

Publications:
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Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT03818386     History of Changes
Other Study ID Numbers: 38RC18.085
First Posted: January 28, 2019    Key Record Dates
Last Update Posted: April 5, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Neoplasm Metastasis
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases