Meningioma, Malignant

This clinical trial tests the safety and effectiveness of hypofractionated stereotactic radiosurgery for treating patients who have undergone surgical resection for grade II meningiomas or grade I meningiomas that have come back after a period of improvement (recurrent). Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Stereotactic radiosurgery is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Hypofractionated stereotactic radiosurgery may be safe, tolerable, and effective in treating patients with grade II or recurrent grade I meningiomas after surgical resection.

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.