NCT03267836

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

Terminated Phase 1 Last updated 15 June 2023

What this trial tests

Phase 1 trial testing Avelumab in Meningioma in 9 participants. Terminated before completion.

Timeline

10 January 2018

Primary endpoint
6 April 2023

6 April 2023

Quick facts

Lead sponsor	Washington University School of Medicine
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	9
Start date	10 January 2018
Primary completion	6 April 2023
Estimated completion	6 April 2023
Sites	1 location across United States

Drugs / interventions tested

• Avelumab (avelumab) — full drug profile →
• Proton Therapy
• Surgery

Conditions studied

• Meningioma — all drugs for Meningioma →
• Meningioma, Adult — all drugs for Meningioma, Adult →

Sponsor

Washington University School of Medicine

Who can join

18 and older, any sex, with Meningioma or Meningioma, Adult. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. An overview of meningiomas.
   Buerki RA, Horbinski CM, Kruser T, Horowitz PM, et al · · 2018 · cited 325× · PMID 30084265 · DOI 10.2217/fon-2018-0006
2. Meningioma: A Review of Epidemiology, Pathology, Diagnosis, Treatment, and Future Directions.
   Ogasawara C, Philbrick BD, Adamson DC. · · 2021 · cited 183× · PMID 33801089 · DOI 10.3390/biomedicines9030319
3. Meningioma: International Consortium on Meningiomas consensus review on scientific advances and treatment paradigms for clinicians, researchers, and patients.
   Wang JZ, Landry AP, Raleigh DR, Sahm F, et al · · 2024 · cited 100× · PMID 38695575 · DOI 10.1093/neuonc/noae082
4. Meningioma: not always a benign tumor. A review of advances in the treatment of meningiomas.
   Maggio I, Franceschi E, Tosoni A, Nunno VD, et al · · 2021 · cited 100× · PMID 34015955 · DOI 10.2217/cns-2021-0003
5. Meningioma: A Review of Clinicopathological and Molecular Aspects.
   Huntoon K, Toland AMS, Dahiya S. · · 2020 · cited 96× · PMID 33194703 · DOI 10.3389/fonc.2020.579599
6. Product review: avelumab, an anti-PD-L1 antibody.
   Collins JM, Gulley JL. · · 2019 · cited 62× · PMID 30481100 · DOI 10.1080/21645515.2018.1551671
7. Proton beam therapy for cancer in the era of precision medicine.
   Hu M, Jiang L, Cui X, Zhang J, et al · · 2018 · cited 57× · PMID 30541578 · DOI 10.1186/s13045-018-0683-4
8. Emerging systemic treatment options in meningioma.
   Mair MJ, Berghoff AS, Brastianos PK, Preusser M. · · 2023 · cited 47× · PMID 36181606 · DOI 10.1007/s11060-022-04148-8