Regorafenib for Recurrent meningioma | Meningioma

Inclusion criteria

• {"criterion_text":"- Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted\n- 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.\n- Patients capable of taking oral medication\n- Subject is willing and able to adhere to the study visit schedule and other protocol requirements.\n- Histological diagnosis of meningioma according to the WHO 2021 classification\n- Radiologically documented progression of any existing tumor with an estimated planar growth >25% (bidirectional) in the last 12 months or appearance of new lesions\n- Ineligible for further surgery and/or radiotherapy\n- at least 1 Measurable lesion (minimum 10 x 10mm) on baseline MRI\n- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 (or KPS ³70)\n- Male or female ≥ 18 years of age\n- 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.\n- Subjects must have life expectancy of at least 6 months\n- Paraffin-embedded tumor tissue available (mandatory)\n- Dosage of dexamethasone or equivalent steroid within 7 days prior the randomization ≤4mg/die\n- Stable or decreasing dosage of steroids for 7 days prior to the randomization.\n- Adequate cardiac function and adequate liver, renal and hematological function\n- 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\n- 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.\n- 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.\n- Possible prior use of bevacizumab in the treatment of radionecrosis (3-24 months after radiosurgery or radiotherapy; 5mg/kg q14w, 4-6 cycles)"}

Exclusion criteria

• {"criterion_text":"- 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)\n- Are taking strong UGT1A9 inhibitors (e.g. mefenamic acid, diflunisal and niflumic acid)\n- Persistent ≥ Grade 3 Lipase (> 2.0 - 5.0 x upper limit of normal [ULN] with signs or symptoms; > 5.0 x ULN and asymptomatic).\n- Receiving additional, concurrent, active therapy for Meningioma outside of the trial.\n- Persistent proteinuria > 3.5 g/24 hours measured by urine protein creatinine ratio from a random urine sample (≥ Grade 3, CTCAE 5.0)\n- Have any malabsorbition condition\n- 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).\n- Disease outside the brain (ie. spinal cord or bone or metastasis to a distant organ)\n- Candidate for urgent palliative intervention for primary disease (e.g., impending herniation. as judged by the Investigator\n- History of allergy or hypersensitivity to any of the study treatments or any of their excipients.\n- 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)\n- Any cerebrovascular accident (including transient ischemic attacks. within the last 6 months prior to initiation of study treatment.\n- Unable or unwilling to undergo brain MRI scans with intravenous (IV) gadolinium\n- 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.\n- Serious, non-healing wound, ulcer, bone fracture, or abscess.\n- Subject incapacitated to understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted\n- Have an ongoing infection with severity of Grade 2 or above (CTCAE 5.0)\n- 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.\n- Uncontrolled intercurrent illness including (e.g., symptomatic ascites), but not limited to ongoing or active infection.\n- 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).\n- 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.\n- Active, known, or suspected auto-immune disease, including systemic lupus erythematosus, Hashimotos thyroiditis, scleroderma, polyarteritis nodosa, or auto-immune hepatitis.\n- 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.\n- History of bleeding diathesis (irrespective of severity).\n- Prior antineoplastic therapy for meningioma"}

Primary endpoints

• {"endpoint_text":"- The progression free survival (PFS) will be determined as the time from the date of randomization to the date of disease progression determined using RANO criteria or to the date of death, whichever occurs first. Patients without a PFS event at the time of analysis will be censored at the date of last assessment.","definition_or_measurement_approach":"PFS defined as time from randomization to disease progression using RANO criteria or death; censoring at date of last assessment for patients without event."}

Secondary endpoints

• {"endpoint_text":"- The overall survival (OS) will be determined as the time from the date of randomization to the date of death from any cause. Patients alive at the time of analysis will be censored at the date of last assessment.","definition_or_measurement_approach":"OS defined as time from randomization to death from any cause; censoring at date of last assessment."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"ORR = % patients with CR or PR per modified Macdonald criteria."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"DCR = % patients with CR, PR or SD per modified Macdonald criteria."}
• {"endpoint_text":"- Quality of life will be assessed by EORTC QLQ-C30 and the QLQBN20 questionnaires. Two HRQOL measures are selected for this study, EORTC QLQ-C30 and the QLQBN20 which have robust psychometric properties resulting from their use in several international cancer clinical trials. The EORTC QLQ-C30 is a core measure designed to be supplemented with the disease specific module. Both instruments are available in Italian and have followed rigorous forward-backward translation procedures.","definition_or_measurement_approach":"QoL measured using EORTC QLQ-C30 and QLQ-BN20 questionnaires; instruments available in Italian."}
• {"endpoint_text":"- Toxicity during the treatment will be recorded and graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.5. Grade refers to the severity of the adverse event. A grading (severity) scale is provided for each adverse event term.","definition_or_measurement_approach":"Toxicity graded per NCI CTCAE v5.0; severity grades recorded for adverse events."}

Italy

Earliest CTIS Part Ii Submission Date

03-06-2024

Latest Decision Or Authorization Date

19-03-2026

Processing Time Days

654

Number Of Sites

17

Number Of Participants

104

Primary sponsor

Full Name

Istituto Oncologico Veneto

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"Bayer S.p.A.","duties_or_roles":"Monetary support","organisation_type":""}