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

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