Repeated blood–brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2024

Repeated blood–brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial

Alexandre Carpentier
Roger Stupp
Adam Sonabend
Henry Dufour
  • Fonction : Auteur
Bertrand Mathon
François Ducray
  • Fonction : Auteur
Jacques Guyotat
  • Fonction : Auteur
Nathalie Baize
  • Fonction : Auteur
Philippe Menei
  • Fonction : Auteur
John de Groot
  • Fonction : Auteur
Jeffrey Weinberg
Benjamin Liu
Eric Guemas
  • Fonction : Auteur
Carole Desseaux
  • Fonction : Auteur
Charlotte Schmitt
  • Fonction : Auteur
Guillaume Bouchoux
  • Fonction : Auteur
Michael Canney
  • Fonction : Auteur
Ahmed Idbaih
  • Fonction : Auteur

Résumé

Abstract Here, the results of a phase 1/2 single-arm trial (NCT03744026) assessing the safety and efficacy of blood-brain barrier (BBB) disruption with an implantable ultrasound system in recurrent glioblastoma patients receiving carboplatin are reported. A nine-emitter ultrasound implant was placed at the end of tumor resection replacing the bone flap. After surgery, activation to disrupt the BBB was performed every four weeks either before or after carboplatin infusion. The primary objective of the Phase 1 was to evaluate the safety of escalating numbers of ultrasound emitters using a standard 3 + 3 dose escalation. The primary objective of the Phase 2 was to evaluate the efficacy of BBB opening using magnetic resonance imaging (MRI). The secondary objectives included safety and clinical efficacy. Thirty-three patients received a total of 90 monthly sonications with carboplatin administration and up to nine emitters activated without observed DLT. Grade 3 procedure-related adverse events consisted of pre syncope ( n = 3), fatigue ( n = 1), wound infection ( n = 2), and pain at time of device connection ( n = 7). BBB opening endpoint was met with 90% of emitters showing BBB disruption on MRI after sonication. In the 12 patients who received carboplatin just prior to sonication, the progression-free survival was 3.1 months, the 1-year overall survival rate was 58% and median overall survival was 14.0 months from surgery.

Dates et versions

hal-04508905 , version 1 (18-03-2024)

Identifiants

Citer

Alexandre Carpentier, Roger Stupp, Adam Sonabend, Henry Dufour, Olivier Chinot, et al.. Repeated blood–brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial. Nature Communications, 2024, 15 (1), pp.1650. ⟨10.1038/s41467-024-45818-7⟩. ⟨hal-04508905⟩
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