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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

Author

Listed:
  • Alexandre Carpentier

    (Sorbonne Université, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurochirurgie)

  • Roger Stupp

    (Northwestern University
    Northwestern University)

  • Adam M. Sonabend

    (Northwestern University
    Northwestern University)

  • Henry Dufour

    (Aix-Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, CHU Timone, Service de Neuro-Oncologie)

  • Olivier Chinot

    (Aix-Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, CHU Timone, Service de Neuro-Oncologie)

  • Bertrand Mathon

    (Sorbonne Université, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurochirurgie)

  • François Ducray

    (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)

  • Jacques Guyotat

    (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)

  • Nathalie Baize

    (CHU Angers)

  • Philippe Menei

    (CHU Angers)

  • John Groot

    (University of California)

  • Jeffrey S. Weinberg

    (The University of Texas MD Anderson Cancer Center)

  • Benjamin P. Liu

    (Northwestern University)

  • Eric Guemas

    (Biossec)

  • Carole Desseaux

    (Carthera)

  • Charlotte Schmitt

    (Carthera)

  • Guillaume Bouchoux

    (Carthera)

  • Michael Canney

    (Carthera)

  • Ahmed Idbaih

    (Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neuro-Oncologie)

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.

Suggested Citation

  • Alexandre Carpentier & Roger Stupp & Adam M. Sonabend & Henry Dufour & Olivier Chinot & Bertrand Mathon & François Ducray & Jacques Guyotat & Nathalie Baize & Philippe Menei & John Groot & Jeffrey S. , 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," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45818-7
    DOI: 10.1038/s41467-024-45818-7
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    Cited by:

    1. Víctor A. Arrieta & Andrew Gould & Kwang-Soo Kim & Karl J. Habashy & Crismita Dmello & Gustavo I. Vázquez-Cervantes & Irina Palacín-Aliana & Graysen McManus & Christina Amidei & Cristal Gomez & Silpol, 2024. "Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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