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Radiosensitization of Multiple Brain Metastases Using AGuIX Gadolinium Based Nanoparticles (NANO-RAD)

This study is currently recruiting participants.
Verified October 2017 by University Hospital, Grenoble
Sponsor:
ClinicalTrials.gov Identifier:
NCT02820454
First Posted: July 1, 2016
Last Update Posted: October 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
NH TherAguix SAS
Information provided by (Responsible Party):
University Hospital, Grenoble
  Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. AGuIX particles may increase the effectiveness of radiation therapy by making tumor cells more sensitive to radiation.

PURPOSE: This first-in-man Phase I trial will study the side effects and best dose of AGuIX when injected together with whole brain radiation therapy in treating patients with multiple brain metastases. The effectiveness of the combination of AGuIX and radiation therapy will be also assessed.


Condition Intervention Phase
Brain Metastases Drug: AGuIX Radiation: whole brain radiation therapy Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Etude Clinique de Phase I de Radiosensibilisation de métastases cérébrales Par Nanoparticules de Gadolinium

Further study details as provided by University Hospital, Grenoble:

Primary Outcome Measures:
  • Maximum-tolerated dose (MTD) of polysiloxane gadolinium-chelates based nanoparticles (AGuIX) given concurrently to the whole brain radiation therapy for the treatment of multiple brain metastases [ Time Frame: 18 months ]
    To determine Maximum-tolerated dose (MTD) of polysiloxane gadolinium-chelates based nanoparticles (AGuIX) given concurrently to the whole brain radiation therapy, according to incidence of dose limiting toxicity (DLT) graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03


Secondary Outcome Measures:
  • Pharmacokinetic characteristics of AGuIX particles after intravenous injection [ Time Frame: 18 months ]
    Cmax

  • Pharmacokinetic characteristics of AGuIX particles after intravenous injection [ Time Frame: 18 months ]
    AUC

  • Pharmacokinetic characteristics of AGuIX particles after intravenous injection [ Time Frame: 18 months ]
    T1/2

  • Distribution of AGuIX particles in brain metastases and surrounding healthy tissue evaluated by MRI [ Time Frame: 30 months ]
    Measure of the T1 contrast enhancement in brain metastases and surrounding healthy tissue after intravenous administration of AGuIX particles

  • Intracranial progression-free survival [ Time Frame: 12 months after radiation ]
    The intracranial progression-free survival will be assessed by MRI (1,3, 6, 9 and 12 months from the date of discovery of the metastases)

  • Overall survival [ Time Frame: 30 months ]
    The overall survival will be assessed starting from the date of discovery of the metastases


Estimated Enrollment: 18
Actual Study Start Date: June 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AGuIX and radiotherapy

Patients receive a single intravenous injection of AGuIX on day 1. Then patients undergo a whole brain radiation therapy, 5 days a week in weeks 1-2. The first radiotherapy session will be performed 4 hours after AGuIX injection.

Five dose escalation cohorts : 15 mg/kg, 30mg/kg, 50mg/kg, 75mg/kg and 100 mg/kg

Drug: AGuIX
A single intravenous injection on day 1. Dose level 1: 15mg/kg; Dose level 2: 30mg/kg, Dose level 3: 50mg/kg; Dose level 4: 75mg/kg; Dose level 5: 100mg/kg
Other Name: Nano-sized gadolinium particles
Radiation: whole brain radiation therapy
30Gy in 10 sessions of 3Gy (5 days a week in weeks 1-2); first session 4 hours after AGuIX injection.

Detailed Description:

The present study will investigate the safety, tolerability and spectrum of side effects of AGuIX in combination with whole brain radiation therapy. As such, this study will characterize the dose limiting toxicities (DLT) and maximum tolerated dose (MTD) of in combination with whole brain radiation therapy in patients with multiple brain metastases.

On day 1, patients will receive a single intravenous injection of AGuIX. An MRI scan will be performed 2 hours after injection to visualize the distribution of AGuIX in brain metastases and surrounding healthy tissue, and to evaluate the contrast enhancement in brain metastases. Then patients will undergo a whole brain radiation therapy, starting 4 hours after AGuIX injection, up to completion of 2 weeks, 5 days a week of treatment (30Gy, 3Gy/fraction).

During the first 24h after injection, several blood draws will be also performed in order to assess the pharmacokinetic of AGuIX.

After completion of study treatment, patients will be followed periodically.

Patients will be enrolled in cohorts and will be treated at sequentially rising dose levels of AGuIX combined with whole brain radiation therapy. Three subjects will initially enter at each dose. If none of the three experiences a dose-limiting toxicity we will proceed to the next dose. If one of the three experiences that level of toxicity, we will accrue 3 more subjects at that dose. If at any time there are two or more dose-limiting toxicities (in the 3-6 subjects) on a given dose, we will drop down to a lower dose. Dose escalation will continue until the MTD of AGuIX and whole brain radiation therapy is established. The MTD will then be one dose below the DLT occurring in at least 1 out of 3 subjects (2 out of 6 patients).

  Eligibility

Information from the National Library of Medicine

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

Inclusion criteria:

  • Patients with brain metastasis ineligible for local treatment by surgery or stereotactic radiation
  • At least 18 years old
  • Secondary brain metastases from a histologically confirmed solid tumor
  • Patient competent to give informed consent (ou Signed informed consent after informing the patient)
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3
  • No prior brain irradiation
  • No renal insufficiency (glomerular filtration rate > 60 mL/min/1.73m²)
  • Normal liver function (bilirubin < 30 µmol/L; Alkaline phosphatase < 400 UI/L; Aspartate aminotransferase (AST) < 75 UI/L; Alanine aminotransferase (ALT) < 175 UI/L)
  • For both male and female patients, effective methods of contraception must be used throughout the study. Acceptable methods of contraception are oral or implantable contraceptives, intrauterine device, condoms, spermicidal gels, or surgical sterilization.
  • Affiliated to a social security scheme or assimilated

Exclusion criteria:

  • Meningeal carcinomatosis
  • Progressive and threatening extracranial disease
  • Previous cranial irradiation (whether whole or partial brain radiation therapy, except stereotactic irradiation) or total body irradiation
  • Known contra-indication, sensitivity or allergy to gadolinium
  • Patients unable to undergo or tolerate Magnetic Resonance Imaging
  • Patients participating in another clinical investigation at the time
  • Protected persons under articles L1121-5 to L1121-8, Code of Public Health
  Contacts and Locations
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): NCT02820454


Contacts
Contact: Camille VERRY, MD 33 4 76 76 54 35 cverry@chu-grenoble.fr
Contact: Géraldine Le Duc, PhD 33 6 87 12 10 40 leduc@nhtheraguix.com

Locations
France
University Hospital Grenoble Recruiting
Grenoble, France, 38100
Contact: Camille VERRY       CVerry@chu-grenoble.fr   
Sponsors and Collaborators
University Hospital, Grenoble
NH TherAguix SAS
Investigators
Principal Investigator: Camille VERRY, MD University Hospital, Grenoble
  More Information

Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT02820454     History of Changes
Other Study ID Numbers: 38RC15.278
2015-004259-30 ( EudraCT Number )
First Submitted: June 2, 2016
First Posted: July 1, 2016
Last Update Posted: October 5, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by University Hospital, Grenoble:
AGuIX
polysiloxane gadolinium-chelates based nanoparticles

Additional relevant MeSH terms:
Neoplasm Metastasis
Brain Neoplasms
Brain Diseases
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Central Nervous System Diseases
Nervous System Diseases