Phase 1/2a clinical trial (NCT02253212) data on ultrasound-induced blood-brain barrier (BBB) opening for brain disorders like recurrent glioblastoma.
CarThera has revealed preliminary data pertaining to its phase 1/2a clinical trial (NCT02253212) on ultrasound-induced blood-brain barrier (BBB) opening for brain disorders like recurrent glioblastoma.
The data was presented by Ahmed Idbaih, MD, PhD, the principal investigator and neuro-oncologist at Assistance Publique — Hôpitaux (AP-HP) in Paris as part of a Poster Discussion session at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, Illinois.
SonoCloud is a low-intensity pulsed ultrasound device that temporarily increases the permeability of the BBB and enhances delivery of therapeutic molecules to the brain. Since the BBB inhibits most drugs from passing through the blood to the brain, it may also be the cause of the limited efficacy of current chemotherapies in recurrent glioblastoma patients; developers aim to address this issue with SonoCloud.
“We are excited to share promising preliminary data from our clinical trial at the ASCO annual meeting attended by more than 32,000 oncology professionals from around the world,” said Dr Idbaih in a recent statement. “The sonication of larger volumes of brain in recurrent glioblastoma. will be investigated in a future trial and may further enhance the observed effectiveness of this new treatment modality.”
The trial included 21 patients with recurrent glioblastoma who were treated monthly with the SonoCloud device prior to carboplatin chemotherapy, which amounted to 85 SonoCloud treatments. A good safety profile and trends in improvement of progression-free survival (PFS) and overall survival (OS) were observed with the treatment. OS was found to increase from 8.5 to 12.9 months in patients who had SonoCloud-induced BBB opening.
Methods for the trial included implanting glioblastoma patients with (1) or (3) 1 MHz, 10-mm diameter cranial devices in burr holes during debulking surgery or during a dedicated procedure under local anesthesia. Using a Simon titration design, ultrasound doses were escalated. To transiently disrupt the BBB before IV administration of carboplatin (AUC4-6), the device was activated monthly. By utilizing MRIs, BBB disruption was visualized, and patients were monitored clinically.
According to the results, which evaluated 85 ultrasound sessions, BBB disruption was evident on post-sonication T1w MRI for 72 sonications and was dependent on the ultrasound dose. A partial seizure, 2 cases of transient edema (H1 and D15) and 1 transient facial palsy were among the few transient and manageable severe related adverse events observed; no carboplatin-related neurotoxicity occurred.
All patients treated with (1) emitter experienced tumor progression and 3/19 patients were alive. Patients with no or poor BBB disruption (n = 8) had a median PFS of 13 weeks and a median OS of 8.9 months in this cohort. A median PFS of 15 weeks and a median OS of 13 months was observed in patients with clear BBB disruption (n = 11).
“Preliminary efficacy results presented by Dr Idbaih at the annual ASCO meeting demonstrate the proof of concept of our first-in-class solution to enhance delivery of therapeutic agents in the brain,” said Frederic Sottilini, CEO of CarThera. “The increase in survival observed in [recurrent glioblastoma] patients paves the way for the combination of the SonoCloud device with different agents for treating various brain disorders, such as cancers and neurodegenerative diseases.”
Looking forward, future trials will be conducted in order to further assess the observed effectiveness the sonication of larger volumes of brain in recurrent glioblastoma.