NCT03267836

Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma

A Phase Ib Study of Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Meningioma is the most common central nervous system (CNS) tumor and accounts for approximately 30% of all CNS tumors. For meningioma recurring after surgery and radiation therapy, there is no effective medical therapy. Repeat surgery or radiation therapy may be possible, but they are temporizing measures with limited durable relief. PD-L1 expression in meningioma is increased for recurrent tumors or prior radiation therapy, and a recent case study reported significant reduction of an intracranial meningioma after 6 months of PD-L1 blockade. Radiation has been shown to augment immune response when combined with PD-L1 blockade. Proton radiation therapy has higher relative biological effectiveness (RBE) and may further amplify the above immunological signals. Combination of proton radiation therapy administered concurrently with PD-L1 inhibitor may maximize immune response for recurrent meningioma. However, confirmation of the increased immunogenicity or increased tumor infiltrating lymphocytes using the combination of radiation therapy and PD-L1 blockade have not been confirmed in patients. The proposed study will be a single institution, single-arm, open-label, phase Ib study to combine neoadjuvant avelumab (a PD-L1 inhibitor) with hypofractionated proton therapy of 20 CGE (cobalt gray equivalent) over 5 fractions followed by planned surgery for recurrent radiation-refractory meningioma. This study is designed to provide proof of concept to demonstrate on-target effect of the combination to increase immunogenicity by directly examining the resected tumor for immune response and to evaluate preliminary clinical efficacy

Conditions

• Meningioma
• Meningioma, Adult

Interventions

Type	Name	Description
DRUG	Avelumab	-10mg/kg IV
RADIATION	Proton Therapy	-Proton therapy will start concurrently with the first dose of avelumab (up to 3 days before or after is permissible) and will be administered once daily during weekdays (Monday through Friday).
PROCEDURE	Surgery	-Standard of care

Timeline

• Start date: 2018-01-10
• Primary completion: 2023-04-06
• Completion: 2023-04-06
• First posted: 2017-08-30
• Last updated: 2023-06-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study