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 x 10^9 / L without granulocyte colony-stimulating
factor support.
2. Platelet Count ≥ 100 x 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 x upper limit of normal (ULN).
2. Aspartate transaminase (AST) ≤ 3 x ULN without liver metastasis.
3. Alanine transaminase (ALT) ≤ 3 x ULN without liver metastasis.
4. AST or ALT ≤ 5 x ULN for patients with liver metastasis.
5. Patients with known Gilbert's syndrome may be included if total bilirubin ≤ x 3
ULN.
7. Patients must have measurable disease by iRANO 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 < 1.3x the laboratory ULN.
Exclusion Criteria. 1. Prior treatment with cabozantinib.
2. Patients < 18 years old.
3. Patients who are pregnant or breast-feeding.
4. Any other active malignancy at time of first dose of study treatment or diagnosis of
another malignancy within 3 years prior to the 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. Correct 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:
1. Cardiovascular disorders:
2. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina
pectoris, serious cardiac arrhythmias.
3. Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg
systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
4. Stroke [including transient ischemic attack (TIA)], myocardial infarction (MI),
or other ischemic event, or thromboembolic event [e.g., deep venous thrombosis
(DVT), pulmonary embolism (PE)] within 6 months before first dose of study
treatment.
5. 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.
6. Gastrointestinal (GI) disorders including those associated with a high risk of
perforation or fistula formation:
7. 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.
8. 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
