Regorafenib for Recurrent Meningioma (MIRAGE Trial)

NCT06275919 | Recruiting Phase 2

• 1 other identifier: IOV-BT-1-2023 MIRAGE
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 17

Brief 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.

Conditions

Meningioma, Malignant

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  The progression free survival (PFS) will be determined as the time from the date of enrolment to the date of disease progression determined using RANO criteria or to the date of death, whichever occurs first.

  Up to 36 months

Secondary Outcomes (6)

• Overall survival (OS)

  Up to 30 months

• Objective response rate (ORR)

  Up to 30 months

• Patient Reported Outcomes (PROs)

  Up to 30 months

• Patient Reported Outcomes (PROs)

  Up to 30 months

• Toxicity during treatment

  Up to 30 months

Study Arms (2)

Arm A (interventional arm)

EXPERIMENTAL

REGORAFENIB 40 mg tablets once daily (160 mg/die), 3 weeks on, 1 week off, until disease progression or unacceptable toxicity

Drug: Regorafenib 40 MG Oral Tablet

Arm B (control arm)

ACTIVE COMPARATOR

Local Standard of Care until disease progression or unacceptable toxicity

Drug: Local Standard of Care

Interventions

Regorafenib 40 MG Oral Tablet DRUG

REGORAFENIB 40 mg tablets once daily (160 mg/die), 3 weeks on, 1 week off, until disease progression or unacceptable toxicity

Arm A (interventional arm)

Local Standard of Care DRUG

In this setting there are not drugs with indication. Every site will treat patients as per their experience.

Arm B (control arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
• Patients capable of taking oral medication
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Histological diagnosis of meningioma according to the WHO 2021 classification
• Radiologically documented progression of any existing tumor with an estimated planar growth \>25% (bidirectional) in the last 12 months or appearance of new lesions
• Ineligible for further surgery and/or radiotherapy
• at least 1 Measurable lesion (minimum 10 x 10mm) on baseline MRI
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 (or KPS ³70)
• Male or female ≥ 18 years of age
• Subjects must have life expectancy of at least 6 months
• Paraffin-embedded tumor tissue available (mandatory)
• Dosage of dexamethasone or equivalent steroid within 7 days prior the randomization ≤4mg/die
• Stable or decreasing dosage of steroids for 7 days prior to the randomization.
• Adequate cardiac function and adequate liver, renal and hematological function
• Subject must have the following laboratory values at screening within 14 days before starting Regorafenib:

You may not qualify if:

• Prior antineoplastic therapy for meningioma
• Subject incapacitated to understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
• Are taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort)
• Are taking strong UGT1A9 inhibitors (e.g. mefenamic acid, diflunisal and niflumic acid)
• Receiving additional, concurrent, active therapy for Meningioma outside of the trial.
• Disease outside the brain (ie. spinal cord or bone or metastasis to a distant organ)
• Candidate for urgent palliative intervention for primary disease (e.g., impending herniation) as judged by the Investigator
• History of allergy or hypersensitivity to any of the study treatments or any of their excipients.
• In the presence of therapeutic intent to anticoagulate the patient:,INR or PT and aPTT not within therapeutic limits (according to the medical standard in the institution)
• Unable or unwilling to undergo brain MRI scans with intravenous (IV) gadolinium
• History of another malignancy in the previous 3 years, with a disease-free interval of\< 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
• Serious, non-healing wound, ulcer, bone fracture, or abscess.
• Any cerebrovascular accident (including transient ischemic attacks) within the last 6 months prior to initiation of study treatment.
• Have an ongoing infection with severity of Grade 2 or above (CTCAE 5.0)
• Any hemorrhage or bleeding event that is ≥ Grade 3 based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE), Grade 2 intracranial hemorrhage, or persistent thrombotic/embolic event within 4 weeks prior to the start of study medication.

Sponsors & Collaborators

• Istituto Oncologico Veneto IRCCS: lead
• Bayer: collaborator

Study Sites (17)

IRST Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"

Meldola, Forlì-Cesena, Italy

RECRUITING

Azienda Ospedaliera Universitaria Gaetano Martino

Messina, Italia/Messina, 98124, Italy

NOT YET RECRUITING

Humanitas Cancer Center

Rozzano, Milano, Italy

RECRUITING

A.O.U. Policlinico di Bari

Bari, Italy

RECRUITING

Ospedale San Paolo

Bari, Italy

COMPLETED

Ospedale Bellaria - AUSL Bologna

Bologna, Italy

RECRUITING

Azienda Ospedaliero Universitaria Careggi

Florence, Italy

RECRUITING

Policlinico San Martino

Genova, Italy

RECRUITING

Spedali Riuniti

Livorno, Italy

RECRUITING

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Italy

RECRUITING

IRCCS Ospedale San Raffaele

Milan, Italy

RECRUITING

Ospedale del Mare

Naples, Italy

RECRUITING

Istituto Oncologico Veneto

Padua, 35128, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, Italy

NOT YET RECRUITING

IRCCS Istituto Tumori Regina Elena

Roma, Italy

RECRUITING

Policlinico Umberto I - Università Sapienza Roma

Roma, Italy

NOT YET RECRUITING

A.O.U. Città della Salute e della Scienza di Torino

Torino, Italy

RECRUITING

Related Publications (1)

• 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.

  PMID: 40759981 DERIVED

MeSH Terms

Conditions

Meningioma

Interventions

regorafenib; Tablets

Condition Hierarchy (Ancestors)

Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Giuseppe Lombardi, MD

  Istituto Oncologico Veneto IOV IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gian Luca De Salvo, MD

CONTACT

049 8215704; gianluca.desalvo@iov.veneto.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2024
• First Posted: February 23, 2024
• Study Start: September 23, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

IT (17)