protocolSection identificationModule nctId: NCT06275919, orgStudyIdInfo id: IOV-BT-1-2023 MIRAGE, briefTitle: Regorafenib for Recurrent Grade 2 and 3 Meningioma (MIRAGE Trial), acronym: MIRAGE, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-06, primaryCompletionDateStruct date: 2026-12, completionDateStruct date: 2027-03, studyFirstPostDateStruct date: 2024-02-23, lastUpdatePostDateStruct date: 2024-03-15, sponsorCollaboratorsModule leadSponsor name: Istituto Oncologico Veneto IRCCS, class: OTHER, collaborators name: Bayer, descriptionModule briefSummary: The focus of this study will be to investigate whether Regorafenib demonstrates antitumor activity against recurrent grade II or III 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., conditionsModule conditions: Meningioma, Malignant, designModule studyType: INTERVENTIONAL, phases: PHASE2, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 104, type: ESTIMATED, armsInterventionsModule interventions name: Regorafenib 40 MG Oral Tablet, interventions name: Local Standard of Care, outcomesModule primaryOutcomes measure: Progression free survival (PFS), secondaryOutcomes measure: Overall survival (OS), secondaryOutcomes measure: Objective response rate (ORR), secondaryOutcomes measure: Patient Reported Outcomes (PROs), secondaryOutcomes measure: Patient Reported Outcomes (PROs), secondaryOutcomes measure: Toxicity during treatment, secondaryOutcomes measure: Disease control rate (DCR), eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: IRST Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori", city: Meldola, state: Forlì-Cesena, country: Italy, contacts name: Lorena Gurrieri, MD, role: CONTACT, email: lorena.gurrieri@irst.emr.it, contacts name: Lorena Gurrieri, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 44.12775, lon: 12.0626, locations facility: Humanitas Cancer Center, city: Rozzano, state: Milano, country: Italy, contacts name: Matteo Simonelli, MD, role: CONTACT, email: matteo.simonelli@hunimed.eu, contacts name: Matteo Simonelli, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.38193, lon: 9.1559, locations facility: Ospedale San Paolo, city: Bari, country: Italy, contacts name: Valeria Internò, MD, role: CONTACT, email: valeria.interno@libero.it, contacts name: Valeria Internò, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 41.11148, lon: 16.8554, locations facility: Ospedale Bellaria - AUSL Bologna, city: Bologna, country: Italy, contacts name: Enrico Franceschi, MD, role: CONTACT, email: e.franceschi@isnb.it, contacts name: Enrico Franceschi, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 44.49381, lon: 11.33875, locations facility: Azienda Ospedaliero Universitaria Careggi, city: Firenze, country: Italy, contacts name: Isacco Desideri, MD, role: CONTACT, email: isacco.desideri@unifi.it, contacts name: Isacco Desideri, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 43.77925, lon: 11.24626, locations facility: Policlinico San Martino, city: Genova, country: Italy, contacts name: Elisa Bennicelli, MD, role: CONTACT, email: elisa.bennicelli@hsanmartino.it, contacts name: Elisa Bennicelli, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 44.40478, lon: 8.94438, locations facility: Spedali Riuniti, city: Livorno, country: Italy, contacts name: Anna Luisa Di Stefano, MD, role: CONTACT, email: annaluisa.distefano@uslnordovest.toscana.it, contacts name: Anna Luisa Di Stefano, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 43.54427, lon: 10.32615, locations facility: Azienda Ospedaliero Universitaria G. Martino, city: Messina, country: Italy, contacts name: Nicola Silvestris, MD, role: CONTACT, email: n.silvestris@unime.it, contacts name: Nicola Silvestris, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 38.19394, lon: 15.55256, locations facility: Fondazione IRCCS Istituto Neurologico Carlo Besta, city: Milano, country: Italy, contacts name: Paola Gaviani, MD, role: CONTACT, email: paola.gaviani@istituto-besta.it, contacts name: Paola Gaviani, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.46427, lon: 9.18951, locations facility: IRCCS Ospedale San Raffaele, city: Milano, country: Italy, contacts name: Giulia Berzero, MD, role: CONTACT, email: berzero.giulia@hsr.it, contacts name: Giulia Berzero, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.46427, lon: 9.18951, locations facility: Ospedale del Mare, city: Napoli, country: Italy, contacts name: Bruno Daniele, MD, role: CONTACT, email: b.daniele@libero.it, contacts name: Bruno Daniele, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 40.85216, lon: 14.26811, locations facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS, city: Roma, country: Italy, contacts name: Silvia Chiesa, MD, role: CONTACT, email: silvia.chiesa@policlinicogemelli.it, contacts name: Silvia Chiesa, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 41.89193, lon: 12.51133, locations facility: IRCCS Istituto Tumori Regina Elena, city: Roma, country: Italy, contacts name: Veronica Villani, MD, role: CONTACT, email: veronica.villani@ifo.it, contacts name: Veronica Villani, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 41.89193, lon: 12.51133, locations facility: Policlinico Umberto I - Università Sapienza Roma, city: Roma, country: Italy, contacts name: Giuseppe Minniti, MD, role: CONTACT, email: giuseppe.minniti@uniroma1.it, contacts name: Giuseppe Minniti, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 41.89193, lon: 12.51133, locations facility: A.O.U. Città della Salute e della Scienza di Torino, city: Torino, country: Italy, contacts name: Roberta Rudà, MD, role: CONTACT, email: roberta.ruda@unito.it, contacts name: Roberta Rudà, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 45.07049, lon: 7.68682, hasResults: False