Cabozantinib for Patients With Recurrent or Progressive Meningioma

Inclusion Criteria 1. Histologic (preferred) or radiologic diagnosis of meningioma. All World Health Organization (WHO) grades (I, II and III) are allowed. 2. All patients must have developed recurrent disease or progressive disease after receiving standard therapy (e.g., radiation or surgery) \> 6 months ago or have been deemed ineligible to receive these therapies. 3. Karnofsky Performance Status ≥ 50. 4. Adequate hematologic function: 1. Absolute Neutrophil Count ≥ 1.5 × 10\^9 / L without granulocyte colony-stimulating factor support. 2. Platelet Count ≥ 100 × 10\^9 / L without transfusion. 3. Hemoglobin ≥ 9 g/dL without transfusion within 7 days prior to screening assessment. 5. Adequate renal function: ≥ 30 mL/min according to the Cockcroft-Gault formula. 6. Adequate hepatic function including: 1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN). 2. Aspartate transaminase (AST) ≤ 3 × ULN without liver metastasis. 3. Alanine transaminase (ALT) ≤ 3 × ULN without liver metastasis. 4. AST or ALT ≤ 5 × ULN for patients with liver metastasis. 5. Patients with known Gilbert's syndrome may be included if total bilirubin ≤ 3 × ULN. 7. Patients must have measurable disease by RANO meningioma criteria. 8. Women of childbearing potential must have negative serum pregnancy testing at screening. All women will be considered childbearing potential unless meeting criteria including: 1. Achieved post-menopausal status as defined by cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have follicular stimulation hormone showing postmenopausal state. Women who have been amenorrhoeic for ≥ 12 months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anorexia, low body weight, ovarian suppression, anti-estrogen therapy or other medically inducible reasons. 2. Documented hysterectomy or bilateral oophorectomy surgery. 3. Medically confirmed ovarian failure. 4. Sexually active participants and their partners must agree to use medically accepted methods of contraception during the study and for 4 months after discontinuing study treatment. 9. Recovery of baseline CTCAE v5.0 Grade ≤ 1 toxicity related to prior study treatments unless adverse events are clinically non-significant per investigator's discretion and/or stable on supportive therapy if needed. 10. Patients must be willing and able to comply with trial protocol. This includes adhering to the treatment plan, scheduled visits, laboratory and other study procedures. 11. Serum albumin ≥ 2.8 g/dL. 12. Prothrombin time (PT)/International Normalized Ratio (INR) or partial thromboplastin time (PTT) test \< 1.3 × the laboratory ULN. Exclusion Criteria 1. Prior treatment with cabozantinib. 2. Patients \< 18 years old. 3. Patients who are pregnant or breast-feeding. 4. 4\. Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. 5. Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment. 6. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) with 2 weeks before first dose of study treatment. 7. Ejection fraction (EF) ≤ 50% by echocardiogram (ECHO). Multi-gated acquisition scan (MUGA) should be obtained to estimate EF if quality of ECHO is insufficient. 8. Prior history of hypertensive encephalopathy at any time. 9. History of congenital QT syndrome. 10. Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms within 14 days of study registration. If initial QTcF is \> 500 ms, two additional EKGs separated by at least 3 minutes should be performed, and if average of these consecutive results is QTcF is ≤ 500 ms, patient is eligible. 11. Unstable cardiac arrhythmia within 6 months prior to study registration date. 12. Urine Protein-to-Creatinine ratio (UPCR) \>1 mg/mg or 24-hour urine protein \> 1 gram. 13. History of bleeding diathesis or significant unexplained coagulopathy (e.g., in the absence of anticoagulation). 14. Clinical signs or symptoms of gastrointestinal obstruction requiring parenteral hydration, nutrition or feeding tube. 15. Uncontrolled effusion management (pleural effusion, pericardial effusion or ascites) requiring recurrent drainage procedures. 16. Active infection requiring parenteral antibiotic therapy. 17. History of either positive hepatitis C virus (HCV) RNA viral load or detectable anti-HCV antibody; hepatitis B virus (HBV) infection with HBV surface antigen detection and/or positive HBV DNA viral load. 18. Serious non-healing wound, ulcer, or bone fracture requiring intervention within 28 days prior to study registration date. 19. Known hypersensitivity to cabozantinib or any component in formulation. 20. Inability to swallow capsules, known intolerance to cabozantinib or its excipients, known malabsorption syndrome, or other conditions which impair intestinal absorption. 21. Other severe acute or chronic medical conditions, which may increase study risk per treating investigator's discretion. 22. Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following: 1. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH). 2. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor. 23. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: a. Cardiovascular disorders: i. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias. ii. Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment. iii. Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment. iv. Subjects with a diagnosis of incidental, sub-segmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion #6) for at least 1 week before first dose of study treatment. b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. The subject has evidence of any concurrent malignancy invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction. ii. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment. 24. Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 mL) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment. 25. Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease from another malignancy. 26. Other clinically significant disorders that would preclude safe study participation. 1. Serious non-healing wound/ulcer/bone fracture. 2. Uncompensated/symptomatic hypothyroidism. 3. Moderate to severe hepatic impairment (Child-Pugh B or C). 27. Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible