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.

Autor: Carpentier A; Sorbonne Université, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurochirurgie, Paris, France. alexandre.carpentier@aphp.fr., Stupp R; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Sonabend AM; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Dufour H; Aix-Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, CHU Timone, Service de Neuro-Oncologie, Marseille, France., Chinot O; Aix-Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, CHU Timone, Service de Neuro-Oncologie, Marseille, France., Mathon B; Sorbonne Université, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurochirurgie, Paris, France., Ducray F; Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Service de Neuro-Oncologie, Hospices Civils de Lyon, Cancer Research Center of Lyon, INSERM U1052, CNRS UMR 5286, Cancer Cell Plasticity Department, Lyon, France., Guyotat J; Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Service de Neuro-Oncologie, Hospices Civils de Lyon, Cancer Research Center of Lyon, INSERM U1052, CNRS UMR 5286, Cancer Cell Plasticity Department, Lyon, France., Baize N; CHU Angers, Angers, France., Menei P; CHU Angers, Angers, France., de Groot J; Departments of Neurology and Neurosurgery, University of California, San Francisco, CA, USA., Weinberg JS; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Liu BP; Departments of Radiology and Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Guemas E; Biossec, Paris, France., Desseaux C; Carthera, Lyon, France., Schmitt C; Carthera, Lyon, France., Bouchoux G; Carthera, Lyon, France., Canney M; Carthera, Lyon, France., Idbaih A; Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neuro-Oncologie, Paris, France.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 23; Vol. 15 (1), pp. 1650. Date of Electronic Publication: 2024 Feb 23.
DOI: 10.1038/s41467-024-45818-7
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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