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 CarpentierRoger StuppAdam M SonabendHenry DufourOlivier Louis ChinotBertrand MathonFrançois DucrayJacques GuyotatNathalie BaizePhilippe MeneiJohn de GrootJeffrey S WeinbergBenjamin P LiuEric GuemasCarole DesseauxCharlotte SchmittGuillaume BouchouxMichael CanneyAhmed IdbaihPublished in: Nature communications (2024)
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.
Keyphrases
- blood brain barrier
- magnetic resonance imaging
- phase iii
- free survival
- phase ii study
- clinical trial
- contrast enhanced
- open label
- cerebral ischemia
- minimally invasive
- light emitting
- computed tomography
- diffusion weighted imaging
- phase ii
- end stage renal disease
- newly diagnosed
- ejection fraction
- study protocol
- ultrasound guided
- chronic kidney disease
- chronic pain
- bone mineral density
- locally advanced
- contrast enhanced ultrasound
- low dose
- randomized controlled trial
- gestational age
- double blind
- postmenopausal women
- coronary artery disease
- preterm birth
- surgical site infection
- pulmonary embolism
- physical activity
- body composition
- tyrosine kinase
- sleep quality
- percutaneous coronary intervention