Bosio Alberto, Cerretti Giulia, Padovan Marta, Del Bianco Paola, Polano Maurizio, Mandruzzato Susanna, Indraccolo Stefano, Manara Renzo, Librizzi Giovanni, Caccese Mario, Corrà Martina, Maccari Marta, Lonardi Sara, De Salvo Gian Luca, Lombardi Giuseppe
Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Trials. 2025 Aug 4;26(1):268. doi: 10.1186/s13063-025-08997-2.
Regorafenib is an oral multi-tyrosine kinase (RTK) inhibitor. It exhibits high selectivity for VEGFR1/2/3, while also inhibiting PDGFRβ, FGFR1, and oncogenic signaling cascades involving c-RAF/RAF1 and BRAF. These pathways are highly expressed in meningiomas, particularly in high-grade meningiomas.
The MIRAGE trial (NCT06275919) is a multicenter, open-label, controlled, randomized phase 2 clinical trial evaluating grade 2/3 meningioma patients who have progressed following surgery and radiotherapy. A total of 94 participants are being randomized (1:1) to receive either regorafenib (160 mg orally for 3 weeks on, 1 week off) or local standard-of-care therapies (e.g., bevacizumab, hydroxyurea, somatostatin analogs). Major inclusion criteria include histological confirmation of grade 2 or grade 3 meningioma according to the WHO 2021 classification, radiologically documented progression according to RANO criteria with at least 1 measurable lesion (minimum 10 × 10 mm) on baseline MRI, ineligibility for further surgery and/or radiotherapy, and a WHO performance status of 0-1. The primary endpoint is 6-month progression-free survival (6m-PFS) and secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and health-related quality of life. Exploratory analysis will also be performed. MIRAGE, initiated in September 2024, is an academic trial promoted by the Istituto Oncologico Veneto, IOV-IRCCS, and will recruit patients across 15 neuro-oncology centers in Italy with an estimated study duration of 18 months.
MIRAGE is a phase 2 trial designed to determine the role of regorafenib in prolonging the PFS of grade 2-3 meningioma patients ineligible for further surgery and/or radiotherapy.
ClinicalTrials.gov NCT06275919. Registered before start of inclusion, 7 February 2024. EuCT no. 2024-510954-28.
瑞戈非尼是一种口服多酪氨酸激酶（RTK）抑制剂。它对血管内皮生长因子受体1/2/3（VEGFR1/2/3）具有高度选择性，同时还可抑制血小板衍生生长因子受体β（PDGFRβ）、成纤维细胞生长因子受体1（FGFR1）以及涉及c-RAF/RAF1和BRAF的致癌信号级联反应。这些通路在脑膜瘤中高度表达，尤其是在高级别脑膜瘤中。
MIRAGE试验（NCT06275919）是一项多中心、开放标签、对照、随机2期临床试验，评估2/3级脑膜瘤患者在手术和放疗后病情进展的情况。共有94名参与者被随机分组（1:1），分别接受瑞戈非尼（口服160 mg，连续服用3周，停药1周）或局部标准治疗方案（如贝伐单抗、羟基脲、生长抑素类似物）。主要纳入标准包括根据世界卫生组织2021年分类经组织学确诊为2级或3级脑膜瘤，根据RANO标准经影像学记录病情进展且基线磁共振成像（MRI）上至少有1个可测量病灶（最小10×10 mm），不适合进一步手术和/或放疗，以及世界卫生组织体能状态为0-1。主要终点是6个月无进展生存期（6m-PFS），次要终点包括总生存期（OS）、客观缓解率（ORR）、疾病控制率（DCR）、安全性和健康相关生活质量。还将进行探索性分析。MIRAGE试验于2024年9月启动，是由威尼斯肿瘤研究所（IOV-IRCCS）推动的一项学术试验，将在意大利的15个神经肿瘤中心招募患者，预计研究持续时间为18个月。
MIRAGE试验是一项2期试验，旨在确定瑞戈非尼在延长不适合进一步手术和/或放疗的2-3级脑膜瘤患者无进展生存期方面的作用。
ClinicalTrials.gov NCT06275919。于纳入开始前，即2024年2月7日注册。欧盟临床试验编号2024-510954-28。
