Radiotherapy of Multiple Brain Metastases Using AGuIX®

NCT03818386 | Unknown Phase 2 DMC

• 1 other identifier: 38RC18.085
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 14

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.

Conditions

Brain Metastases, Adult; Radiotherapy

Keywords

gadolinium nanoparticles; AGuIX

Outcome Measures

Primary Outcomes (2)

• Best objective intracranial response rate - intent-to-treat

  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

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

  at 3 months

Secondary Outcomes (12)

• Evaluation of the quality of life

  at D0, 6 weeks, 3, 6, 9, 12 months

• Evaluation of the quality of life

  at day 0, 6 weeks, 3, 6, 9, 12 months

• Neurocognitive evaluation

  at Day 0, 6 weeks, 3, 6, 9, 12 months

• Best objective intracranial response rate - per-protocol

  at 6 weeks and 3 months

• Evaluation of the intracranial response rate

  for 12 months

Study Arms (2)

AGuIX® + Whole Brain Radiation Therapy

EXPERIMENTAL

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®; Radiation: Whole Brain Radiation Therapy

Whole Brain Radiation Therapy

ACTIVE COMPARATOR

Intervention: Radiation: Whole Brain Radiation Therapy ( WBRT) 30 Gy in 10 fractions of 3 Gy over 2-3 weeks

Radiation: Whole Brain Radiation Therapy

Interventions

AGuIX® DRUG

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

Also known as: Gadolinium-chelated polysiloxane based nanoparticles

AGuIX® + Whole Brain Radiation Therapy

Whole Brain Radiation Therapy RADIATION

30 Gy in 10 fractions of 3 Gy over 2-3 weeks

Also known as: WBRT

AGuIX® + Whole Brain Radiation Therapy; Whole Brain Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Grenoble: lead
• NH TherAguix SAS: collaborator

Study Sites (14)

Institut Régional du Cancer

Montpellier, Occitanie, 34298, France

Location

Institut Claudius Regaud Institut Universitaire du Cancer Toulouse Oncopole Radiothérapie

Toulouse, Occitanie, 31059, France

Location

Centre Leon Berard Lyon

Lyon, Rhones Alpes, 69373, France

Location

Centre Hospitalier Annecy Genevois

Annecy, Rhones-Alpes, 74374, France

Location

Centre Hospitalier Universitaire Grenoble-Alpes

Grenoble, Rhones-Alpes, 38700, France

Location

CRLCC - Institut Bergonié

Bordeaux, 33000, France

Location

Crlcc Francois Baclesse

Caen, 14000, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Hospices Civils de Lyon-Hôpital Lyon Sud

Lyon, 69495, France

Location

Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

La Pitié Salpêtrière - Charles Foix

Paris, 75651, France

Location

Institut Curie Saint Cloud

Saint-Cloud, 92210, France

Location

Crlcc Paul Strauss

Strasbourg, 67085, France

Location

Institut de Cancérologie de Lorraine ALEXIS VAUTRIN

Vandœuvre-lès-Nancy, 54519, France

Location

Related Publications (3)

• Le Duc G, Miladi I, Alric C, Mowat P, Brauer-Krisch E, Bouchet A, Khalil E, Billotey C, Janier M, Lux F, Epicier T, Perriat P, Roux S, Tillement O. Toward an image-guided microbeam radiation therapy using gadolinium-based nanoparticles. ACS Nano. 2011 Dec 27;5(12):9566-74. doi: 10.1021/nn202797h. Epub 2011 Nov 9.

  PMID: 22040385 BACKGROUND

• Lux F, Tran VL, Thomas E, Dufort S, Rossetti F, Martini M, Truillet C, Doussineau T, Bort G, Denat F, Boschetti F, Angelovski G, Detappe A, Cremillieux Y, Mignet N, Doan BT, Larrat B, Meriaux S, Barbier E, Roux S, Fries P, Muller A, Abadjian MC, Anderson C, Canet-Soulas E, Bouziotis P, Barberi-Heyob M, Frochot C, Verry C, Balosso J, Evans M, Sidi-Boumedine J, Janier M, Butterworth K, McMahon S, Prise K, Aloy MT, Ardail D, Rodriguez-Lafrasse C, Porcel E, Lacombe S, Berbeco R, Allouch A, Perfettini JL, Chargari C, Deutsch E, Le Duc G, Tillement O. AGuIX(R) from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine. Br J Radiol. 2019 Jan;92(1093):20180365. doi: 10.1259/bjr.20180365. Epub 2018 Sep 18.

  PMID: 30226413 BACKGROUND

• Verry C, Dufort S, Barbier EL, Montigon O, Peoc'h M, Chartier P, Lux F, Balosso J, Tillement O, Sancey L, Le Duc G. MRI-guided clinical 6-MV radiosensitization of glioma using a unique gadolinium-based nanoparticles injection. Nanomedicine (Lond). 2016 Sep;11(18):2405-17. doi: 10.2217/nnm-2016-0203. Epub 2016 Aug 16.

  PMID: 27529506 BACKGROUND

MeSH Terms

Conditions

Brain Neoplasms

Interventions

AGuIX

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Camille VERRY, MD

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The main endpoint will be evaluated by a blinded endpoint committee.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective Randomized Open Blinded Endpoint phase II clinical trial.

Study Record Dates

• First Submitted: December 11, 2018
• First Posted: January 28, 2019
• Study Start: March 26, 2019
• Primary Completion: June 26, 2024
• Study Completion: March 26, 2025
• Last Updated: June 14, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (14)