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Histologic (preferred) or radiologic diagnosis of meningioma. All WHO grades (I, II and III) are allowed |
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All patients must have developed recurrent disease or progressive disease after receiving standard therapy (eg, radiation or surgery) >6 months ago or have been deemed ineligible to receive these therapies |
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Karnofsky Performance Status ≥50 (Appendix 1) |
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Adequate Hematologic Function |
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(1) Absolute Neutrophil Count ≥ 1.5 x 10^9 / L without granulocyte colony-stimulating |
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factor support |
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(2) Platelet Count ≥ 100 x 10^9 / L without transfusion. (3) Hemoglobin ≥ 9 g/dL without |
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transfusion within 7 days prior to screening assessment |
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Adequate Renal Function ≥ 30 ml/min according to the Cockcroft-Gault formula (Appendix |
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) 6. Adequate Hepatic Function including |
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(1) Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (2) AST ≤ 3 x upper limit of normal |
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(ULN) without liver metastasis (3) ALT ≤ 3 x upper limit of normal (ULN) without liver |
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metastasis (4) AST or ALT ≤ 5 x upper limit of normal (ULN) for patients with liver |
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metastasis (5) Patients with known Gilbert's syndrome may be included if total bilirubin ≤ |
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x 3 ULN 7. Patients must have measurable disease by iRANO criteria (Section [13.2.2.1](telnet://13.2.2.1)) 8 |
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Women of childbearing potential must have negative serum pregnancy testing at screening |
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All women will be considered childbearing potential unless meeting criteria including |
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(1) Achieved post-menopausal status as defined by cessation of regular menses for at least |
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consecutive months with no alternative pathological or physiological cause and have |
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follicular stimulation hormone showing postmenopausal state. Women who have been |
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amenorrhoeic for ≥12 months are still considered to be of childbearing potential if the |
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amenorrhea is possibly due to prior chemotherapy, anorexia, low body weight, ovarian |
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suppression, anti-estrogen therapy or other medically inducible reasons |
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(2) Documented hysterectomy or bilateral oophorectomy surgery (3) Medically confirmed |
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ovarian failure (4) Sexually active participants and their partners must agree to use |
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medically accepted methods of contraception during the study and for 4 months after |
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discontinuing study treatment (Section 11.4) |
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Recovery of baseline CTCAE v5.0 Grade ≤1 toxicity related to prior study treatments |
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unless adverse events are clinically non-significant per investigator's discretion and/or |
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stable on supportive therapy if needed |
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Patients must be willing and able to comply with trial protocol. This includes adhering |
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to the treatment plan, scheduled visits, laboratory and other study procedures |
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Serum albumin ≥ 2.8 g/dl 12. (PT)/INR or partial thromboplastin time (PTT) test < 1.3x |
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the laboratory ULN |
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Prior treatment with cabozantinib
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Patients <18 years old
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Patients who are pregnant or breast-feeding
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Any other active malignancy at time of first dose of study treatment or diagnosis of
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another malignancy within 3 years prior to first dose of study treatment that requires
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active treatment, except for locally curable cancers that have been apparently cured
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such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma
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in situ of the prostate, cervix, or breast
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Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy
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(including investigational) within 4 weeks before first dose of study treatment
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Receipt of any type of small molecule kinase inhibitor (including investigational kinase
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inhibitor) within 2 weeks before first dose of study treatment
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Ejection Fraction (EF) ≤50% by echocardiogram (ECHO). Multi-gated acquisition scan
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(MUGA) should be obtained to estimate EF if quality of ECHO is insufficient
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Prior history of hypertensive encephalopathy at any time 10. History of congenital QT
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syndrome. 11. Corrected QT interval calculated by the Fridericia formula (QTcF) >500 ms
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within 14days of study registration (Appendix 6). If initial QTcF is >500 ms, two
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additional EKGs separated by at least 3 minutes should be performed, and if average of
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these consecutive results is QTcF is ≤ 500 ms, patient is eligible
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Unstable cardiac arrhythmia within 6 months prior to study registration date
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Urine Protein-to-Creatinine ratio (UPCR) >1 mg/mg or 24-hour urine protein > 1 gram
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(Appendix 5) 14. History of bleeding diathesis or significant unexplained coagulopathy (eg
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in the absence of anticoagulation)
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Clinical signs or symptoms of gastrointestinal obstruction requiring parenteral
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hydration, nutrition or feeding tube
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Uncontrolled effusion management (pleural effusion, pericardial effusion or ascites)
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requiring recurrent drainage procedures
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Active infection requiring parenteral antibiotic therapy. 18. History of either
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positive HCV RNA viral load or detectable anti-HCV antibody; HBV infection with HBV surface
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antigen detection and/or positive HBV DNA viral load
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Serious non-healing wound, ulcer, or bone fracture requiring intervention within 28
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days prior to study registration date
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Known hypersensitivity to cabozantinib or any component in formulation. 21. Inability
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to swallow capsules, known intolerance to cabozantinib or its excipients, known
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malabsorption syndrome, or other conditions which impair intestinal absorption
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Other severe acute or chronic medical conditions, which may increase study risk per
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treating investigator's discretion
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Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin
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inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet
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inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following
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a. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable
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guidelines) and low-dose low molecular weight heparins (LMWH)
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b. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors
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rivaroxaban, edoxaban, or apixaban in subjects who are on a stable dose of the
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anticoagulant for at least 1 week before first dose of study treatment without clinically
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significant hemorrhagic complications from the anticoagulation regimen or the tumor
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The subject has uncontrolled, significant intercurrent or recent illness including, but
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not limited to, the following conditions
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Cardiovascular disorders
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Congestive heart failure New York Heart Association Class 3 or 4, unstable angina
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pectoris, serious cardiac arrhythmias
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Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg
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systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment
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Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or
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other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary
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embolism) within 6 months before first dose of study treatment
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Subjects with a diagnosis of incidental, sub-segmental PE or DVT within 6 months are
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allowed if stable, asymptomatic, and treated with a stable dose of permitted
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anticoagulation (see exclusion criterion #6) for at least 1 week before first dose of
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study treatment
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Gastrointestinal (GI) disorders including those associated with a high risk of
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perforation or fistula formation
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The subject has evidence of any concurrent malignancy invading the GI tract, active
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peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease)
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diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute
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pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric
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outlet obstruction
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Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess
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within 6 months before first dose of study treatment
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Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of
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study treatment
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Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml)
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of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within
|
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weeks before first dose of study treatment
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Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease from
|
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another malignancy
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Other clinically significant disorders that would preclude safe study participation
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Serious non-healing wound/ulcer/bone fracture
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Uncompensated/symptomatic hypothyroidism
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Moderate to severe hepatic impairment (Child-Pugh B or C). 28. Major surgery (e.g
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laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2
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weeks before first dose of study treatment. Minor surgeries within 10 days before
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first dose of study treatment. Subjects must have complete wound healing from major
|
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surgery or minor surgery before first dose of study treatment. Subjects with
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clinically relevant ongoing complications from prior surgery are not eligible
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