Symptoms and General Pathology

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Nervous System Diseases

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Meningioma

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

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

Local Standard of Care until disease progression or unacceptable toxicity

Regorafenib 40 MG Oral Tablet

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

Local Standard of Care

Gian Luca De Salvo, MD

Lorena Gurrieri, MD

Matteo Simonelli, MD

Valeria Internò, MD

Enrico Franceschi, MD

Isacco Desideri, MD

Elisa Bennicelli, MD

Anna Luisa Di Stefano, MD

Nicola Silvestris, MD

Paola Gaviani, MD

Giulia Berzero, MD

Bruno Daniele, MD

Silvia Chiesa, MD

Veronica Villani, MD

Giuseppe Minniti, MD

Roberta Rudà, MD

Giuseppe Lombardi, MD

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.

Regorafenib for Recurrent Grade 2 and 3 Meningioma (MIRAGE Trial)

Regorafenib for Recurrent Grade 2 and 3 Meningioma. A Multicenter, Randomized Phase II Study (MIRAGE Trial)

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.

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

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.

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

Quality of life will be assessed by the QLQBN20 questionnaire.

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

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.

Bayer

Istituto Oncologico Veneto IRCCS

Sintilimab will be administered every 3 weeks Sintilimab will be administered through IV infusion

Sintilimab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells

Sintilimab

Feng Chen

This research study is studying a drug as a possible treatment for High Grade Meningioma.

Meningioma is one of the most common primary intracranial tumors, accounting for 13% to 26% of all intracranial tumors. Although most meningiomas are benign tumors and can be cured by surgical resection, more than 20% of WHO II (atypical) and about 3% of WHO III meningiomas are more likely to have local recurrence after initial treatment , And the lifetime is poor. The immunotherapy represented by PD-1 has achieved remarkable efficacy in the treatment of solid tumors, but the application of PD-1 in recurrent meningioma is rarely reported. The study found that the expression of PD-L1 mRNA and protein in high-grade meningioma cells increased, and the total number of T cells, including CD4+ and CD8+ cells, was significantly reduced, suggesting an inhibitory tumor immune microenvironment. Recent studies have shown that giving patients anti-PD-1 antibody immunotherapy prior to conventional treatment can improve the pathological response, enable the body to produce an enhanced and sustained anti-tumor immune response, and form a tumor microenvironment conducive to immunotherapy. Therefore, giving PD-1 antibody before surgery is a new idea for the treatment of meningiomas. This project aims to investigate whether patients with recurrent meningioma will change their immune function and prolong survival after preoperative PD-1 antibody treatment. It is planned to use flow cytometry, multiple immunofluorescence histochemistry technology, T cell receptor sequencing, etc to detect the changes in the patient's immune function before and after treatment, observe the pathological remission rate of PD-1 monoclonal antibody neoadjuvant treatment of recurrent meningioma, and identify potential response biomarkers, and conduct in-depth discussions on this treatment plan to further determine the treatment mode Clinical value and specific mechanism of action in order to improve the clinical treatment level of patients with recurrent meningioma.

Exploratory Study of PD-1 Neoadjuvant Treatment of Recurrent Meningioma

Contrast-enhanced cranial MRI will be performed every 6 weeks. PFS6 is defined as not having progressive disease or death within six months of the first day of treatment. Contrast-enhanced cranial magnetic resonance imaging (MRI) will be performed every 6 weeks.

The distributions of overall survival will be summarized using the method of Kaplan-Meier. The follow-up of patients who are alive at the time of analysis will be censored at the date of last assessment of vital status. Median OS will be presented and accompanied by 90% confidence intervals estimated using log(-log(survival)) methodology. Survival point estimates at 3 and 6 months will also be presented with confidence intervals.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Regorafenib for Recurrent Grade 2 and 3 Meningioma (MIRAGE Trial)	NCT06275919	Meningioma, Mal...	Regorafenib 40 ... Local Standard ...	18 Years -	Istituto Oncologico Veneto IRCCS
Exploratory Study of PD-1 Neoadjuvant Treatment of Recurrent Meningioma	NCT04728568	Meningioma, Mal...	Sintilimab	18 Years - 70 Years	Beijing Tiantan Hospital

Spots Global Cancer Trial Database for meningioma, malignant