E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with brain metastases, from a histologically confirmed solid tumor, eligible for WBRT |
Métastases cérébrales multiples d’un cancer prouvé histologiquement |
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E.1.1.1 | Medical condition in easily understood language |
Patients with brain metastases eligible for WBRT |
Patients avec des métastases cérébrales éligibles à la radiothérapie |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006128 |
E.1.2 | Term | Brain metastases |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The Objective Intracranial Response is defined as having intracranial Complete Response (CR) or intracranial Partial Response (PR) for brain metastasis, assessed by contrast-enhanced MRI using RECIST v1.1 criteria. |
Meilleur taux de réponse intracrânien objectif (à 6 semaines et 3 mois) |
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E.2.2 | Secondary objectives of the trial |
- Quality of life test (EORTC QLQ C30 and EORTC QLQ BN20) - Neurocognitive test (MoCA) - Evaluation of brain metastases response on Per protocol population, according to RECIST v1.1 criteria (or modified RECIST), by MRI at 6 weeks and 3 months, with MRI centralized reading on Per protocol - 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 - Evaluation of individual brain metastasis response, for all metastases with the sum of diameters > 1cm, by MRI rate at 6 weeks and 3, 6, 9 and 12 months - Death related to brain metastases progression - Death - Reporting of daily steroid dose - MRI evaluation of contrast enhancement at D0 after AGuIX® injection - Reporting of adverse events by type, frequency and severity for both treatments (WBRT and AGuIX® + WBRT). |
- Evaluation de la qualité de vie - Evaluation neurocognitive - Evaluation de la réponse intracrânienne à 6 semaines, 3, 6, 9 et 12 mois - Evaluation de la réponse individuelle des métastases à 6 semaines, 3, 6, 9 et 12 mois - Survie sans progression intracrânienne - Survie à 6 mois - Survie cérébrale - Survie globale - Changement dans la dépendance aux stéroïdes - Etude par IRM de la distribution et de l’élimination du produit dans les métastases cérébrales - Incidence événements indésirables |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Objective: MRI evaluation of the distribution and quantification of AGuIX® in brain metastases after injection of AGuIX®- Population: 20 patients |
Evaluation par IRM de la cinétique de distribution et d’accumulation de l’AGuIX® dans les métastases cérébrales après la troisième injection d’AGuIX® (20 patients). |
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E.3 | Principal 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) performans 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 - No renal insufficiency (glomerular filtration rate ≥ 50 mL/min/1.73m²) - Affiliated to a social security regimen - Effective methods of contraception must be used throughout the study . |
- Métastases cérébrales multiples d’un cancer prouvé histologiquement, éligible à l’IET - Age ≥ 18 ans sans limite d’âge supérieure - Capacité de consentement éclairé écrit et signé - Statut ECOG 0-2 - Pathologie extra-crânienne : o Réponse complète, partielle ou stabilisés sous traitement systémique o Pas de pathologie extra-crânienne o Ou en traitement de première ligne - Espérance de vie > 6 mois - Absence d’insuffisance rénale (DFG ≥ 50 mL/min/1.73m²) - Affilié à un régime de sécurité social ou bénéficiaire d’un tel régime - Méthode de contraception efficace sur toute la durée de l’étude |
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E.4 | Principal 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 - Inclusion in another clinical trial protocol - Pregnancy or breastfeeding - Subject in exclusion period of another study - Subject under administrative or judicial control |
- Pathologie leptiméningée - Preuve d’une métastase avec hémorragie importante récente - Pathologie extra-crânienne en progression sous traitement systémique - Antécédent d’irradiation crânienne (à l’exception d’une irradiation stéréotaxique) - Contre-indication, hypersensibilité ou allergie connue au gadolinium - Contre-indication connue à l’IRM - Inclusion dans un autre essai clinique - Femme enceinte ou parturiente - Personnes décrites aux articles L1121-6 et L1121-8 (personnes privées de liberté par une décision judiciaire ou administrative, personnes majeures faisant l’objet d’une mesure de protection légale ou hors d’état d’exprimer leur consentement) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of brain metastases response, according to RECIST v1.1 criteria (or modified RECIST), by MRI at 6 weeks and 3 months, with MRI centralized reading |
Evaluation de la taille et de la réponse de métastases cérébrales basée sur les critères RECIST v1.1 (ou RECIST modifié) par IRM à 6 semaines et 3 mois, par lecture centralisée des IRM. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 weeks and 3 months |
6 semaines et 3 mois |
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E.5.2 | Secondary end point(s) |
- Quality of life test (EORTC QLQ C30 and EORTC QLQ BN20) - Neurocognitive test (MoCA) - Evaluation of brain metastases response on Per protocol population, according to RECIST v1.1 criteria (or modified RECIST), by MRI at 6 weeks and 3 months, with MRI centralized reading on Per protocol - 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 - Evaluation of individual brain metastasis response, for all metastases with the sum of diameters > 1cm, by MRI rate at 6 weeks and 3, 6, 9 and 12 months - Death related to brain metastases progression - Death - Reporting of daily steroid dose - MRI evaluation of contrast enhancement at D0 after AGuIX® injection - Reporting of adverse events by type, frequency and severity for both treatments (WBRT and AGuIX® + WBRT). |
- Questionnaires de qualité de vie (EORTC QLQ C30 et EORTC QLQ BN20) - Tests neurocognitifs (MoCA) - Evaluation de la taille et de la réponse des métastases cérébrales par les critères RECIST v1.1 et RANO, et par l’évolution de la somme des diamètres les plus longs (pour toutes les métastases avec une somme de diamètres > 1cm) par IRM à 6 semaines, 3, 6, 9 et 12 mois. - Evaluation de la réponse individuelle des métastases pour toutes les métastases avec une somme des diamètres > 1 cm, par IRM à 6 semaines, 3, 6, 9 et 12 mois - Décès lié à la progression des métastases cérébrales - Décès - Dose journalière de stéroïde - Evaluation par IRM de la majoration de contraste à J0 après injection d’AGuIX® - Recueil des évènements indésirables par type, fréquence et sévérité pour les deux bras de traitement
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 weeks, 3, 6, 9 and 12 months |
6 semaines, 3, 6, 9 et 12 mois |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | |