Regorafenib for recurrent grade 2 and 3 meningioma. A multicenter, randomized phase II study (MIRAGE trial)
- Conditions
- grade 2 and 3 meningiomaMedDRA version: 21.0Level: LLTClassification code: 10025672Term: Malignant meningioma Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2024-510954-28-01
- Lead Sponsor
- Istituto Oncologico Veneto
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 104
Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted, 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: a. Absolute neutrophil count (ANC) = 1.5 x 109/L without growth factor support for 7 days (14 days if subject received pegfilgrastim). b. Hemoglobin (Hgb) =10 g/dL c. Platelet count (plt) =100x 109/L d. Serum potassium concentration within normal range, or correctable with supplements e. 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). f. Serum total bilirubin = 1.5 x ULN g. 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. h. Serum albumin > 3.5 g/dL i. 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., 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 grade 2 or grade 3 meningioma according to the WHO 2021 classification, Radiologically documented progression (estimated planar growth >15%- measured in two dimensional tumor area- within the prior 6 months or a new lesion develops), 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
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), 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)., Receiving additional, concurrent, active therapy for Meningioma outside of the trial., 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)., 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), Any cerebrovascular accident (including transient ischemic attacks. within the last 6 months prior to initiation of study treatment., 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., Subject incapacitated to understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted, Are taking strong UGT1A9 inhibitors (e.g. mefenamic acid, diflunisal and niflumic acid), 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, polyarteriti
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method