Regorafenib for Recurrent Meningioma (MIRAGE Trial)

Summary

The focus of this study will be to investigate whether Regorafenib demonstrates antitumor activity against recurrent meningiomas. Small trials and case series suggest clinical relevant activity of several VEGF inhibitors such as sunitinib, bevacizumab and valatinib reporting a 6m-PFS rate of 42-64%. Indeed, VEGF and VEGF receptors (VEGFR) are regularly overexpressed in meningiomas and can correlate with outcome. Regorafenib inhibits angiogenic receptor tyrosine kinases (RTKs) and is highly selective for VEGFR1/2/3; moreover Regorafenib inhibits PDGFRB, FGFR1 and oncogenic intracellular signalling cascades involving c-RAF/RAF1 and BRAF highly expressed in meningiomas. Noteworthy, Regorafenib showed antitumor activity in vitro and in vivo in a recent study; indeed, Regorafenib showed significant inhibition of meningioma cell motility and invasion and in vivo, mice with orthotopic meningioma xenografts showed a reduced volume of signal enhancement in MRI following Regorafenib therapy; this translated in a significantly increased overall survival time (p\<0.05) for Regorafenib treated mice. Moreover, Regorafenib showed good efficacy in different cancer types, such as colorectal cancer, GIST, hepatocellular carcinoma and glioblastoma (REGOMA trial) , maintainingmaintaining a good quality of life.

Timeline

Start

2024-09-23

Primary completion

2026-12

Completion

2027-03

Publications

• Bosio A, Cerretti G, Padovan M, Del Bianco P, Polano M, Mandruzzato S, Indraccolo S, Manara R, Librizzi G, Caccese M, Corra M, Maccari M, Lonardi S, De Salvo GL, Lombardi G. Regorafenib versus local standard of care in patients with grade 2-3 meningioma no longer eligible for loco-regional treatments: a phase II randomized controlled trial (the MIRAGE study). Trials. 2025 Aug 4;26(1):268. doi: 10.1186/s13063-025-08997-2.

Drugs

Indications