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

PRIMARY OBJECTIVES:

I. To determine progression free survival (PFS) for 6 months (PFS-6) in patients with
recurrent or progressive meningioma.

SECONDARY OBJECTIVES:

I. To determine overall survival (OS). II. To determine tumor response rate (TRR). III. To
assess quality of life with treatment (QOL) using Functional Assessment of Cancer
Therapy-Brain (FACT-Br) questionnaire.

OUTLINE:

Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15 of
courses 1-4. Beginning on day 1 of course 5, patients may choose to receive bevacizumab IV
every 3 weeks or remain on the every 2-week schedule. Patients also undergo electric field
therapy using Optune (formerly NovoTTF-200A System) daily over 18 hours. Courses repeat every
28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

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 computed
tomography (CT) scan

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

- Surgical resection, if possible;

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

- Patients may have had previous systemic treatment regimens with the exception of
bevacizumab (no limit to number of prior therapies); a 4 week wash-out period prior to
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 days
prior 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 x
institutional 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 childbearing
potential must agree to use adequate contraception prior to study entry and for the
duration of study treatment; should a female patient become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately; likewise, if the female partner of a male patient becomes pregnant or
suspect she is pregnant, he should inform his treating physician immediately

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 has
not been naturally postmenopausal for > 12 months)

- FOCBP must have a negative serum or urine pregnancy test within 14 days prior to
registration on study

- Patients must have the ability to understand and the willingness to sign a
written 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 weeks
prior to registration, patients who have not recovered from the side effects of any
major surgery (defined as requiring general anesthesia), or patients that may require
major surgery during the course of the study

- Patients who have had minor surgical procedures (with the exception of the placement
of 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 washout
period from prior investigational drug is required)

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

- Previous treatment with bevacizumab

- Patients who have a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to bevacizumab are not eligible

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

- Patients with known sensitivity to conductive hydrogels like the gel used on
electrocardiogram (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 for
proteinuria 2+ (patients discovered to have 2+ proteinuria on dipstick urinalysis at
baseline should undergo a 24-hour urine collection, and must demonstrate =< 1 g of
protein/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 the
absence of therapeutic anticoagulation)

- Patients with history of hematemesis or hemoptysis (defined as having bright red blood
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 mmHg
and /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 prior to
registration

- Chronic, systemic treatment with immunosuppressive agents; patients who require a
stable dose of corticosteroids for control of cerebral edema are eligible; topical or
inhaled steroids are also allowed

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

- Ongoing or active wound infection requiring concurrent systemic antibiotic
treatment; there is no mandatory duration of time that a patient has to be off
antibiotics, but the treating physician has to deem the infection as effectively
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 study
requirements, prevent patient comprehension of the nature of, and risk associated
with, the study

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

- Female patients who are pregnant or nursing are not eligible