Key Points.
- Final results from Carthera’s international phase I/II clinical trial in patients with recurrent glioblastoma (rGBM) have been published in Nature Communications.
- Dose escalation to nine emitters was safe, and the device was efficacious in providing 90% BBB disruption in a larger volume around the rGBM treatment area.
- The median overall survival rate was higher in the group that received carboplatin before BBB disruption.
The results from Carthera’s international phase I/II clinical trial (NCT03744026) in patients with recurrent glioblastoma (rGBM) have been published in Nature Communications. The study enrolled 33 participants across six clinical sites to undergo blood-brain barrier (BBB) disruption with the SonoCloud-9 device before or after intravenous administration of the chemotherapy carboplatin. Four of the sites were in France, and two were in the United States.
The safety and efficacy of the treatment were the primary outcome measures (Phase 1 evaluated the safety of escalating the number of ultrasound emitters and Phase 2 used MRI to evaluate the efficacy of BBB disruption). Survival data were also collected.
Carthera designed the SonoCloud-9 device with nine emitters in order to disrupt a larger region of the BBB than had been tested in their initial studies with a single emitter (SonoCloud-1). This trial evaluated dose-limiting toxicity as the number of activated emitters was increased in each enrollment cohort.
The 33 participants received a total of 90 sonications (up to 6 cycles) for an average sonication time of 9.9 minutes; three participants also received an additional 11 sonications because the disease was not progressing. Fifty-six percent (56%) of the participants received two or more cycles of ultrasound with carboplatin.
The clinical trial revealed that dose escalation to nine emitters (Phase 1) was safe, and that the device was efficacious in providing 90% BBB disruption in a larger volume around the rGBM treatment area (Phase 2). Device-related adverse events included pre-syncope, fatigue, wound infections, and temporary severe pain during device connection. Adverse events reported during treatment included scalp pain, nausea, dizziness, headache, aphasia, and blurred vision. All but one case of blurred vision resolved within 15 minutes after the treatment ended.
Regarding whether to give the carboplatin before or after BBB disruption, the median overall survival rate in the 12 participants who were treated with carboplatin before sonication with all nine emitters was 14.0 months from surgery, and their overall survival rate at 1 year was 58%. This was superior to the 15 participants who received carboplatin after BBB disruption; their median overall survival was 11.8 months, and their one-year overall survival rate was 47%.
“The publication of our clinical results in the highly respected Nature Communications journal demonstrates the significance of the SonoCloud technology as a potentially viable new treatment option for patients with recurrent glioblastoma,” said Professor Alexandre Carpentier, head of the neurosurgery department at Greater Paris University Hospitals – AP-HP Sorbonne Université University, inventor of SonoCloud, and founder of Carthera.
What is next: A Phase III registrational clinical trial is now underway to continue evaluating whether the combination treatment offers improved overall survival compared with the standard of care. Phase III is called SONOBIRD, and it randomizing participants to either the SonoCloud-9/carboplatin combination treatment or current standard of care chemotherapy treatments (with temozolomode or lomustine).
For Patients
Interested patients should consult clinicaltrials.gov (https://www.clinicaltrials.gov/study/NCT05902169) for an updated list of actively enrolling clinical sites. Additional information can be obtained by emailing contact@carthera.eu.
See Nature Communications (Open Access)
See Carthera’s Press Release
Media Coverage: Medical Device Network
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