A Phase 2a Trial of Immune Modulation in Combination With Ultrasound-mediated Blood Brain Barrier Opening in Patients With Newly Diagnosed Glioblastoma
Northwestern University
Summary
Brain tumor treatment is hampered by the blood-brain barrier (BBB). This barrier prevents drugs carried in the bloodstream from getting into the brain. If the BBB can be opened, making it temporarily more permeable, drugs may able to better reach the brain tumor. In this trial we will implant a novel device with 9 ultrasound emitters, allowing temporary and reversible opening of the BBB to maximize brain penetration of drugs that modulate the immune system. The device will be implanted after radiation is completed. Immune modulating drugs will be given every 3 weeks in conjunction with activation of the device to open the BBB. The objectives of this trial are to establish whether it is safe and feasible to administer immune modulating drugs in this manner, and identify whether the treatment is effective in treating glioblastoma.
Description
Eligible patients will undergo implant of the Soncloud-9 device within 1-5 weeks of completion of radiotherapy. About 1-3 weeks after surgery, patients will undergo sonication and intravenous administration of balstilimab, botensilimab and liposomal doxorubicin. Brain MRI will be done to quantify extent of blood brain barrier opening. The dose for balstilimab is 450 mg every 3 weeks. The dose for botensilimab is 1mg/kg every 6 weeks. The dose for liposomal doxorubicin is 30 mg every 3 weeks. Sonication and administration of study agents will continue every 3 weeks (21 days= 1 cycle) for a tota…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Have newly diagnosed pathologically proven glioblastoma, isocitric dehydrogenase-1/2 wild-type * Tumor with methyl guanine methyl transferase (MGMT) gene promoter unmethylated * Available paraffin embedded tumor tissue for the study * Have completed standard radiotherapy with or without temozolomide * 18 years of age or older * Able to undergo contrast-enhanced MRI * Have an Eastern Cooperative Oncology Group/World Health Organization performance status ≤ 2 * Size and location of the residual tumor and/or resection cavity must allow to be able to be covered by the sonica…
Interventions
- DrugBalstilimab
Balstilimab 450 mg IV over 30 minutes every 3 weeks
- DrugBotensilimab
Botensilimab1mg/kg mg IV over 30 minutes every 6 weeks
- DrugLiposomal Doxorubicin
Liposomal Doxorubicin 30 mg IV over 30 minutes every 3 weeks
- DeviceSonocloud-9 (SC-9)
Device activation of 9 ultrasound emitters during IV injection of microbubbles every 3 weeks
Location
- Northwestern UniversityChicago, Illinois