Radiotherapy of Multiple Brain Metastases Using AGuIX®
- Conditions
- Brain Metastases, AdultRadiotherapy
- Interventions
- Radiation: Whole Brain Radiation Therapy
- Registration Number
- NCT03818386
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 100
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AGuIX® + Whole Brain Radiation Therapy AGuIX® 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 Whole Brain Radiation Therapy Whole Brain Radiation Therapy Intervention: Radiation: Whole Brain Radiation Therapy ( WBRT) 30 Gy in 10 fractions of 3 Gy over 2-3 weeks AGuIX® + Whole Brain Radiation Therapy 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
- Primary Outcome Measures
Name Time Method 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
Name Time Method Evaluation of the quality of life at day 0, 6 weeks, 3, 6, 9, 12 months Quality of life test score EORTC QLQ BN20
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)
MRI study of the distribution of the product in brain metastases Day 0 MRI evaluation of contrast enhancement at D0 after AGuIX® injection
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
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
Overall survival at 12 months Death
Change in steroid dependence at 6 weeks and 3, 6, 9 and 12 months Reporting of daily steroid dose
Neurocognitive evaluation at Day 0, 6 weeks, 3, 6, 9, 12 months Neurocognitive test (MoCA)
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
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
Intracranial progression-free survival, brain survival at 12 months Death related to brain metastases progression
Trial Locations
- Locations (14)
Centre Hospitalier Annecy Genevois
🇫🇷Annecy, Rhones-Alpes, France
Centre Leon Berard Lyon
🇫🇷Lyon, Rhones Alpes, France
Centre Hospitalier Universitaire Grenoble-Alpes
🇫🇷Grenoble, Rhones-Alpes, France
CRLCC - Institut Bergonié
🇫🇷Bordeaux, France
Crlcc Francois Baclesse
🇫🇷Caen, France
Centre Georges François Leclerc
🇫🇷Dijon, France
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
La Pitié Salpêtrière - Charles Foix
🇫🇷Paris, France
Institut Curie Saint Cloud
🇫🇷Saint-Cloud, France
Crlcc Paul Strauss
🇫🇷Strasbourg, France
Institut de Cancérologie de Lorraine ALEXIS VAUTRIN
🇫🇷Vandœuvre-lès-Nancy, France
Institut Régional du Cancer
🇫🇷Montpellier, Occitanie, France
Institut Claudius Regaud Institut Universitaire du Cancer Toulouse Oncopole Radiothérapie
🇫🇷Toulouse, Occitanie, France
Hospices Civils de Lyon-Hôpital Lyon Sud
🇫🇷Lyon, France