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Meningioma, MalignantPhase 2MIRAGENCT06275919

Regorafenib for Recurrent Meningioma (MIRAGE Trial)

A Phase 2 study testing Regorafenib 40 MG Oral Tablet in people with Meningioma, Malignant, run by Istituto Oncologico Veneto IRCCS at 20 sites in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

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%. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Meningioma, Malignant
What is being tested?
Regorafenib 40 MG Oral Tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
104 participants
Where
20 sitesItaly
Study dates
23 Sep 2024to Mar 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 29Show fewer
  • 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:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor support for 7 days (14 days if subject received pegfilgrastim).
  • Hemoglobin (Hgb) ≥10 g/dL
  • Platelet count (plt) ≥100x 109/L
  • Serum potassium concentration within normal range, or correctable with supplements
  • Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and serum glutamate pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ≤ 3.0 x Upper Limit of Normal (ULN).
  • Serum total bilirubin ≤ 1.5 x ULN
  • Serum creatinine ≤ 1.5 x ULN or measured glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m2 using an exogenous filtration marker such as iohexol, inulin, 51Cr EDTA or 1125 iothalamate, or creatinine clearance of ≥ 50 mL/min using Cockroft-Gault equation.
  • Serum albumin > 3.5 g/dL
  • PT (or INR) and APTT within normal range
  • For women who are not postmenopausal (i.e., < 2 years after last menstruation) or surgically sterile (absence of ovaries and/or uterus) and who are sexually active: agreement to use an adequate method of contraception (oral contraceptives, intrauterine contraceptive device, or barrier method of contraception in conjunction with spermicidal jelly) during the Treatment period and for at least 6 months after the last dose of study drug.
  • For male patients who are partners of premenopausal women: agreement to use a barrier method of contraception during the Treatment period and for at least 6 months after the last dose of study drug.
  • Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to participate.
  • 19. Patients with measurable, progressive meningioma who received radiation therapy are potentially eligible but need to show evidence of progression at least 24 weeks from completion of radiation therapy.
  • 20. Possible prior use of bevacizumab in the treatment of radionecrosis (3-24 months after radiosurgery or radiotherapy; 5mg/kg q14w, 4-6 cycles)

Who cannot join

  • 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)
Show all 25Show fewer
  • 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.
  • Uncontrolled or severe cardiac disease (e.g., history of unstable angina, myocardial infarction, coronary stenting, or bypass surgery within the last 6 months prior to initiation of study treatment), symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation), requirement for inotropic support or use of devices for cardiac conditions (e.g.,pacemakers/defibrillators), or hypertension (participants with systolic blood pressure[BP] of > 160 mmHg or diastolic BP of > 100 mmHg despite optimal medical management are to be excluded).
  • History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, or symptomatic pleural effusion.
  • Active, known, or suspected auto-immune disease, including systemic lupus erythematosus, Hashimotos thyroiditis, scleroderma, polyarteritis nodosa, or auto-immune hepatitis.
  • Known history of hepatitis B, human immunodeficiency virus (HIV), or active hepatitis C infection requiring treatment with antiviral therapy. Note: HIV testing is not required in the absence of clinical suspicion.
  • History of bleeding diathesis (irrespective of severity).
  • Uncontrolled intercurrent illness including (e.g., symptomatic ascites), but not limited to ongoing or active infection.
  • Persistent ≥ Grade 3 Lipase (> 2.0 - 5.0 x upper limit of normal [ULN] with signs or symptoms; > 5.0 x ULN and asymptomatic).
  • Persistent proteinuria > 3.5 g/24 hours measured by urine protein creatinine ratio from a random urine sample (≥ Grade 3, CTCAE 5.0)
  • Have any malabsorbition condition
  • Any condition that could make the subject noncompliant with the study procedures and/or study requirements, as judged by the Investigator (for example: cognitive impairment, psychiatric illness, etc).

Trial locations and contacts

20 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Gian Luca De Salvo, MD contact

049 8215704 ext. +39

gianluca.desalvo@iov.veneto.it

20 sites in 1 country

Italy20 sites, 19 recruiting

  • Centro di Riferimento Oncologico di Aviano (CRO), IRCCS

    Aviano, Italy, PN, 33081

    Lorenzo Vinante, MD, lorenzo.vinante@cro.it

    Not yet recruiting

  • Ospedale Santa Maria Annunziata

    Bagno a Ripoli, Italy, Firenze, 50012

    Silvia Scoccianti, MD, silvia.scoccianti@uslcentro.toscana.it

    Not yet recruiting

  • A.O.U. Policlinico di Bari

    Bari

    Valeria Internò, valeria.interno@policlinico.ba

    Valeria Internò

    Recruiting

  • Ospedale San Paolo

    Bari

    Completed

  • Ospedale Bellaria - AUSL Bologna

    Bologna

    Enrico Franceschi, MD, e.franceschi@isnb.it

    Enrico Franceschi, MD

    Recruiting

  • Azienda Ospedaliero Universitaria Careggi

    Florence

    Isacco Desideri, MD, isacco.desideri@unifi.it

    Isacco Desideri, MD

    Recruiting

  • Policlinico San Martino

    Genova

    Elisa Bennicelli, MD, elisa.bennicelli@hsanmartino.it

    Elisa Bennicelli, MD

    Recruiting

  • Spedali Riuniti

    Livorno

    Anna Luisa Di Stefano, MD, annaluisa.distefano@uslnordovest.toscana.it

    Anna Luisa Di Stefano, MD

    Recruiting

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

    Meldola, Forlì-Cesena

    Lorena Gurrieri, MD, lorena.gurrieri@irst.emr.it

    Lorena Gurrieri, MD

    Recruiting

  • Azienda Ospedaliera Universitaria Gaetano Martino

    Messina, Italia/Messina, 98124

    Mariacarmela Santarpia, MD, mariacarmela.santarpia@unime.it

    Recruiting

  • Fondazione IRCCS Istituto Neurologico Carlo Besta

    Milan

    Paola Gaviani, MD, paola.gaviani@istituto-besta.it

    Paola Gaviani, MD

    Recruiting

  • IRCCS Ospedale San Raffaele

    Milan

    Nicole Liscia, MD, liscia.nicole@hsr.it

    Nicole Liscia, MD

    Recruiting

  • Ospedale del Mare

    Naples

    Pasqualina Giordano, MD, giopas@email.it

    Bruno Daniele, MD

    Recruiting

  • Istituto Oncologico Veneto

    Padova, 35128

    Giuseppe Lombardi, MD, giuseppe.lombardi@iov.veneto.it

    Recruiting

  • Azienda Ospedaliera di Perugia

    Perugia

    Mario Mandalà, Prof, mario.mandala@unipg.it

    Not yet recruiting

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    Roma

    Silvia Chiesa, MD, silvia.chiesa@policlinicogemelli.it

    Silvia Chiesa, MD

    Recruiting

  • IRCCS Istituto Tumori Regina Elena

    Roma

    Veronica Villani, MD, veronica.villani@ifo.it

    Veronica Villani, MD

    Recruiting

  • Policlinico Umberto I - Università Sapienza Roma

    Roma

    Giuseppe Minniti, MD, giuseppe.minniti@uniroma1.it

    Giuseppe Minniti, MD

    Not yet recruiting

  • Humanitas Cancer Center

    Rozzano, Milano

    Matteo Simonelli, MD, matteo.simonelli@hunimed.eu

    Matteo Simonelli, MD

    Recruiting

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

    Torino

    Roberta Rudà, MD, roberta.ruda@unito.it

    Roberta Rudà, MD

    Recruiting

Other trials in Italy

About this study

Official title: Regorafenib for Recurrent Meningioma. A Multicenter, Randomized Phase II Study (MIRAGE Trial)

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.

Read more

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.

Being tested
Regorafenib 40 MG Oral Tablet, Local Standard of Care
Medical subject headings
Meningioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Regorafenib 40 MG Oral TabletDrug

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

  • Local Standard of CareDrug

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

Study groups in NCT06275919
Study groupRoleWhat they receive
Arm A (interventional arm)ExperimentalREGORAFENIB 40 mg tablets once daily (160 mg/die), 3 weeks on, 1 week off, until disease progression or unacceptable toxicity
Receives: Drug: Regorafenib 40 MG Oral Tablet
Arm B (control arm)Active comparatorLocal Standard of Care until disease progression or unacceptable toxicity
Receives: Drug: Local Standard of Care

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 54 months

Secondary outcomes (6)

  1. Overall survival (OS)

    The overall survival (OS) will be determined as the time from the date of enrolment to the date of death from any cause.

    Measured: Up to 42 months

  2. Objective response rate (ORR)

    The objective response rate (ORR) will be defined as the percentage of patients with complete response (CR) and partial response (PR) determined using modified Macdonald criteria.

    Measured: Up to 42 months

  3. Patient Reported Outcomes (PROs)

    Quality of life will be assessed by EORTC QLQ-C30 questionnaire.

    Measured: Up to 42 months

  4. Patient Reported Outcomes (PROs)

    Quality of life will be assessed by the QLQBN20 questionnaire.

    Measured: Up to 42 months

  5. Toxicity during treatment

    Toxicity during the treatment will be recorded and graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.5.

    Measured: Up to 42 months

  6. Disease control rate (DCR)

    The disease control rate (DCR) will be defined as the percentage of patients with complete response (CR), partial response (PR) and stable disease (SD) determined using modified Macdonald criteria.

    Measured: Up to 42 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2024
  2. Study start23 Sep 2024
  3. Primary completionDec 2028 (estimated)
  4. Study completionMar 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
104 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06275919
Sponsor's protocol ID
IOV-BT-1-2023 MIRAGE
Acronym
MIRAGE
Status last verified
Sep 2026
First submitted
7 Feb 2024
Last updated
30 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

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.

    PubMed 40759981

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Regorafenib 40 MG Oral Tablet in people with Meningioma, Malignant, run by Istituto Oncologico Veneto IRCCS at 20 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Gian Luca De Salvo, MD (049 8215704 ext. +39, gianluca.desalvo@iov.veneto.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (PFS) (time frame: Up to 54 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06275919, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2026.

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