NCT02820454

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Mar 2016

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2016

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

June 2, 2016

Completed
29 days until next milestone

First Posted

Study publicly available on registry

July 1, 2016

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2019

Completed
Last Updated

June 7, 2019

Status Verified

April 1, 2019

Enrollment Period

2.9 years

First QC Date

June 2, 2016

Last Update Submit

June 5, 2019

Conditions

Keywords

AGuIXpolysiloxane gadolinium-chelates based nanoparticles

Outcome Measures

Primary Outcomes (1)

  • 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

    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

    18 months

Secondary Outcomes (6)

  • Pharmacokinetic characteristics of AGuIX particles after intravenous injection

    18 months

  • Pharmacokinetic characteristics of AGuIX particles after intravenous injection

    18 months

  • Pharmacokinetic characteristics of AGuIX particles after intravenous injection

    18 months

  • Distribution of AGuIX particles in brain metastases and surrounding healthy tissue evaluated by MRI

    30 months

  • Intracranial progression-free survival

    12 months after radiation

  • +1 more secondary outcomes

Study Arms (1)

AGuIX and radiotherapy

EXPERIMENTAL

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: AGuIXRadiation: whole brain radiation therapy

Interventions

AGuIXDRUG

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

Also known as: Nano-sized gadolinium particles
AGuIX and radiotherapy

30Gy in 10 sessions of 3Gy (5 days a week in weeks 1-2); first session 4 hours after AGuIX injection.

AGuIX and radiotherapy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital Grenoble

Grenoble, 38100, France

Location

Related Publications (1)

  • Verry C, Sancey L, Dufort S, Le Duc G, Mendoza C, Lux F, Grand S, Arnaud J, Quesada JL, Villa J, Tillement O, Balosso J. Treatment of multiple brain metastases using gadolinium nanoparticles and radiotherapy: NANO-RAD, a phase I study protocol. BMJ Open. 2019 Feb 11;9(2):e023591. doi: 10.1136/bmjopen-2018-023591.

MeSH Terms

Conditions

Brain Neoplasms

Interventions

AGuIX

Condition Hierarchy (Ancestors)

Central Nervous System NeoplasmsNervous System NeoplasmsNeoplasms by SiteNeoplasmsBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Study Officials

  • Camille VERRY, MD

    University Hospital, Grenoble

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 2, 2016

First Posted

July 1, 2016

Study Start

March 1, 2016

Primary Completion

February 1, 2019

Study Completion

February 1, 2019

Last Updated

June 7, 2019

Record last verified: 2019-04

Locations