Optune Delivered Electric Field Therapy and Bevacizumab in Treating Patients With Recurrent or Progressive Grade 2 or 3 Meningioma

Inclusion Criteria:

• Patients must have a histologic diagnosis of meningioma, World Health Organization (WHO) grade 2 or 3 (atypical or anaplastic)

• Patient's tumor must have a supratentorial component

• Patients must have measurable or non-measurable (evaluable) disease recurrence;recurrence must be documented by magnetic resonance imaging (MRI) or computedtomography (CT) scan

• All patients must have developed recurrent disease/progression (evidence ofrecurrence to be established by MRI or CT scan with contrast; there is no limit tothe number of relapses) after receiving all standard treatments, which must includethe following:

• Surgical resection, if possible;

• Definitive radiation therapy for unresectable meningioma, or for recurrentmeningioma after resection (Note: At registration, patients must be at least 28days post-surgery, and must be at least 28 days post-radiation therapy, withresolution of related cytotoxicities down to grade 2)

• Patients may have had previous systemic treatment regimens with the exception ofbevacizumab (no limit to number of prior therapies); a 4 week wash-out period priorto registration is mandatory for all systemic treatments

• Life expectancy of at least 12 weeks

• Karnofsky performance status >= 60%

• Patients must have adequate bone marrow, kidney, and liver function, (within 14 daysprior to registration), defined as:

• Absolute neutrophil count (ANC) >= 1500/uL (with/without growth factor)

• Hemoglobin (Hgb) >= 9 g/dL (with/without transfusion)

• Platelets >= 100,000/L

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 xinstitutional upper limit of normal (ULN)

• Total bilirubin =< 1.5 x institutional ULN

• Serum creatinine =< 1.5 x institutional ULN

• Females of child-bearing potential (FOCBP) and males with partners of childbearingpotential must agree to use adequate contraception prior to study entry and for theduration of study treatment; should a female patient become pregnant or suspect sheis pregnant while participating in this study, she should inform her treatingphysician immediately; likewise, if the female partner of a male patient becomespregnant or suspect she is pregnant, he should inform his treating physicianimmediately

NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy

• Has had menses at any time in the preceding 12 consecutive months (and therefore hasnot been naturally postmenopausal for > 12 months)

• FOCBP must have a negative serum or urine pregnancy test within 14 days priorto registration on study

• Patients must have the ability to understand and the willingness to sign awritten informed consent prior to registration on study

• Patients must be able to comply with all protocol requirements

Exclusion Criteria:

• Patients who have had major surgery or significant traumatic injury within 4 weeksprior to registration, patients who have not recovered from the side effects of anymajor surgery (defined as requiring general anesthesia), or patients that mayrequire major surgery during the course of the study

• Patients who have had minor surgical procedures (with the exception of the placementof porta cath or other central venous access) within 7 days prior to registration

• Patients with infratentorial disease and spinal disease

• Patients may not be receiving any other investigational agents; (i.e. 28-day washoutperiod from prior investigational drug is required)

• Patients may not receive any other anti-cancer therapies, within 28 days prior toregistration and throughout the duration of this trial

• Previous treatment with bevacizumab

• Patients who have a history of allergic reactions attributed to compounds of similarchemical or biologic composition to bevacizumab are not eligible

• Patients with active implanted medical device, a skull defect (such as, missing bonewith no replacement), a shunt or bullet fragments; examples of active electronicdevices include deep brain stimulators, spinal cord stimulators, vagus nervestimulators, pacemakers, defibrillators, and programmable shunts

• Patients with known sensitivity to conductive hydrogels like the gel used onelectrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes

• Patients with proteinuria within 14 days of registration as demonstrated by either:urine protein creatinine (UPC) ratio >= 1.0 at screening OR urine dipstick forproteinuria 2+ (patients discovered to have 2+ proteinuria on dipstick urinalysis atbaseline should undergo a 24-hour urine collection, and must demonstrate =< 1 g ofprotein/24 hours to be eligible)

• Patients with a serious non-healing wound, active ulcer, or untreated bone fracture

• Patients with evidence of bleeding diathesis or significant coagulopathy (in theabsence of therapeutic anticoagulation)

• Patients with history of hematemesis or hemoptysis (defined as having bright redblood of 1/2 teaspoon or more per episode) within 28 days prior to registration

• History of myocardial infarction or unstable angina within 6 months of registration

• Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHgand /or diastolic blood pressure > 100 mmHg)

• History of stroke or transient ischemic attack within 6 months prior to registration

• Any prior history of hypertensive crisis or hypertensive encephalopathy

• History of abdominal fistula or gastrointestinal perforation within 6 months priorto registration

• Chronic, systemic treatment with immunosuppressive agents; patients who require astable dose of corticosteroids for control of cerebral edema are eligible; topicalor inhaled steroids are also allowed

• Patients who have any severe and/or uncontrolled intercurrent medical conditionsincluding, but not limited to any of the following, are not eligible:

• Ongoing or active wound infection requiring concurrent systemic antibiotictreatment; there is no mandatory duration of time that a patient has to be offantibiotics, but the treating physician has to deem the infection aseffectively treated prior to enrollment

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia (New York Heart Association [NYHA] criteria)

• Psychiatric illness/social situations that would limit compliance with studyrequirements, prevent patient comprehension of the nature of, and riskassociated with, the study

• Any other illness or condition that the treating investigator feels wouldinterfere with study compliance or would compromise the patient's safety orstudy endpoints

• Female patients who are pregnant or nursing are not eligible