Pilot Study for the Use of Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma With Mismatch Repair Deficiency: A Phase I Clinical Trial
Jennifer Leddon
Summary
Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma with Mismatch Repair Deficiency.
Description
In this phase I clinical trial, 6-8 patients with recurrent glioblastoma and identified mismatch repair (MMR) deficiency will be administered pembrolizumab along with focused ultrasound sonication following surgery for recurrent glioblastoma. Treatment dosing will be 200mg of pembrolizumab every three weeks for up to six months or until disease progression, whichever occurs first. The primary endpoint will be safety and tolerability, with secondary efficacy endpoints and exploratory biomarker and radiographic analyses
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Patient previously diagnosed with WHO grade 4 IDH-wildtype GBM, determined through genomic and/or histopathological analysis. 2. Prior treatment for GBM with surgical resection and standard of care TMZ and radiation therapy. 3. Patient who has undergone repeat surgery (including biopsy or resection) for rGBM. 4. MMR deficiencies confirmed per standard of care immunohistochemical analysis or Next Generation Sequencing (NGS) of the patient's surgical sample from the time of initial GBM diagnosis or recurrence. 5. Area of sonication using the NaviFUS platform is \>30 mm fr…
Interventions
- DrugPembrolizumab
Treatment dosing will be 200mg of pembrolizumab every three weeks for up to six months or until disease progression, whichever occurs first.
- DeviceNavifus Focused Ultrasound Sonification
Focused Ultrasound Sonification- Post Pembro infusion, patients will received NaviFUS sonication to the complete volume of the tumor resection bed (as limited by anatomic constraints relative to the tumor extension) following microbubble (Bracco Imaging, SonoVue® or Lumason®; 0.1 mL/Kg; maximum 4.8 mL) administration on a 2-minute schedule. The NaviFUS procedure will be guided using the compatible navigation system, Medtronic StealthStation®. Microbubble administration and operation of the NaviFUS unit will be completed by qualified delegated study investigators. Treatment sessions will occur every 3 weeks for 6 months or until evidence of disease progression, whichever occurs first. A 6-month treatment duration was determined in order to report a 6-month PFS rate as one of the secondary outcomes for this study population.
Location
- University of CincinnatiCincinnati, Ohio