Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Gliosarcoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Immunomodulating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Patients will undergo implantation of Sonocloud-9 after completion of radiotherapy. Within 21 days after implant, ultrasound-based BBB opening with concomitant administration of DOX (30 mg) + BAL (450 mg) every 3 weeks, and BOT (dose 1mg/kg) every 6 weeks will be initiated.

Balstilimab 450 mg IV over 30 minutes every 3 weeks

Balstilimab

Botensilimab1mg/kg mg IV over 30 minutes every 6 weeks

Botensilimab

Liposomal Doxorubicin 30 mg IV over 30 minutes every 3 weeks

Liposomal Doxorubicin

Device activation of 9 ultrasound emitters during IV injection of microbubbles every 3 weeks

Sonocloud-9 (SC-9)

Christina Amidei

Nicole Morud

Adam Sonabend, MD

Roger Stupp, MD

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.

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 total of 9 cycles (approx. 6 months). Additional cycles may be considered if deemed beneficial and in the patient's best interest. Blood samples for circulating tumor DNA will also be collected before and after each sonication. The first 6 patients will comprise a safety run-in cohort with intensified safety monitoring through the end of the second cycle.

Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma

A Phase 2a Trial of Immune Modulation in Combination With Ultrasound-mediated Blood Brain Barrier Opening in Patients With Newly Diagnosed Glioblastoma

Patterns of recurrence by magnetic resonance imaging related to sonication field

Analysis of nucleic acid/exosomes and peripheral blood cell for correlation with progression-free survival

Unacceptable toxicity rate in cycle 1 of \< 33%

Overall survival and progression-free survival at 12 and 18 months, as well as median progression-free and overall survival.

Predictive value of baseline tissue p-ERK expression for response/benefit of immunotherapy

Measurement of tumor shrinkage using Response Assessment in Neuro-oncology criteria in those with residual or tumor

Spots Global Cancer Trial Database for botensilimab (bot)