A Phase II Study of Optune (NovoTTF) in Combination With Bevacizumab (BEV) and Temozolomide (TMZ) in Patients With Newly Diagnosed Unresectable Glioblastoma (GBM)

Inclusion Criteria:

* At least 22 years of age
* Have undergone a brain biopsy via stereotactic or open technique
* Pathological evidence of GBM using WHO classification criteria
* Planned 6 weeks of concurrent chemoradiotherapy post-biopsy concomitant with temozolomide (45-70Gy)
* Karnofsky scale greater than or equal to 70
* Life expectancy at least 3 months
* Baseline hemoglobin of \> 8.0 gm/dL (with or without transfusion)
* Adequate coagulation defined as PT and INR \< 1.5 times the upper limit of normal
* Signed informed consent
* Able to start bevacizumab at least 2 weeks but no more than 4 weeks from date of biopsy
* Able to tolerate MRI of brain and have measurable disease.
* Participants of childbearing age must use effective contraception for at least 6 months following completion of treatment.

Exclusion Criteria

* Enrolled in another clinical treatment trial
* Pregnant or Breast-feeding
* Any other malignancy aside from localized basal cell or squamous cell carcinoma of the skin
* Significant co-morbidities at baseline which would prevent maintenance temozolomide
* Thrombocytopenia (platelet count \< 100 x 103 )
* Neutropenia (absolute neutrophil count \< 1.5 x 103 )
* CTC grade 4 non-hematological toxicity (except for alopecia, nausea, vomiting)
* Significant liver function impairment - AST or ALT \> 3 times the upper limit of normal
* Total bilirubin\> 2 times the upper limit of normal
* Significant renal impairment (serum creatinine\> 1.7 mg/dL)
* Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
* Infra-tentorial tumor
* Evidence of increased intracranial pressure (midline shift \> 5mm, clinically significant papilledema, vomiting and nausea, or reduced level of consciousness)
* History of hypersensitivity reaction to temozolomide or a history of hypersensitivity to DTIC or hydrogel
* Inability to adequately cover treatment area with TTFields (Tumor Treating Fields)
* Inability to wear NovoTTF-100A System for an average of 18 hours per 24 hours
* Currently taking cytotoxic medications, non-steroidal ant-inflammatory drugs (NSAIDS), or enzyme inducing anticonvulsants.
* Currently taking anticoagulants or blood-thinners (Coumadin)
* Subjects meeting any of the following bevacizumab-specific contraindications are ineligible for study entry:
* Inadequately controlled hypertension (defined as systolic blood pressure greater than or equal to 150 and/or diastolic blood pressure \> 100 mmHg)
* Prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* History of myocardial infarction or unstable angina within 6 months prior to study enrollment
* History of stroke or transient ischemic attack within 6 months prior to study enrollment
* Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to study enrollment
* History of hemoptysis (greater than or equal to a half teaspoon of bright red blood per episode) within 1 month prior to study enrollment
* Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
* Major surgical procedure or significant traumatic injury within 28 days prior to 1st bevacizumab infusion or anticipation of need for major surgical procedure during the course of the study
* Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
* History of abdominal fistula, gastrointestinal perforation within 6 months prior to study enrollment
* Serious, non-healing wound, active ulcer, or untreated bone fracture
* Proteinuria at screening as demonstrated by either urine protein: creatinine (UPC) ratio greater than or equal to 1.0 at screening OR urine dipstick for proteinuria greater than or equal to 2 or more (patients discovered to have greater than or equal to 2 or greater proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate less than or equal to 1g of protein in 24 hours to be eligible).
* Known hypersensitivity to any component of bevacizumab