Bevacizumab, Electric Field Therapy, and Hypofractionated Radiation Therapy in Treating Patients with Recurrent Glioblastoma

Inclusion Criteria

• Patients with recurrent or progressive glioblastoma or other grade IV malignant glioma (e.g. glioblastoma, gliosarcoma, giant cell glioblastoma, etc.) who have failed prior radiation but who have not progressed/recurred on bevacizumab; patients will be eligible if the original histology was lower-grade glioma and subsequent diagnosis of glioblastoma or gliosarcoma is made
• Patients with any number of recurrences are allowed
• Brain MRI with contrast demonstrates an enhancing tumor =< 8 cm in largest diameter within 30 days prior to registration
• History and physical including neurological exam, height, weight, cranial skin exam, and Karnofsky performance status >= 70% within 30 days prior to registration
• Within 14 days prior to registration: Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
• Within 14 days prior to registration: Platelets >= 100 x 10^9/L
• Within 14 days prior to registration: Hemoglobin (Hgb) >= 9.0 g/dL (note: the use of transfusion or other intervention to achieve Hgb >= 9.0 is acceptable)
• Within 14 days prior to registration: Serum total bilirubin =< 1.5 x upper limit of normal (ULN)
• Within 14 days prior to registration: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN
• Within 14 days prior to registration: Blood urea nitrogen (BUN) and creatinine (Cr) < 2 x ULN
• Minimum interval since completion of radiation treatment is 12 weeks
• History of central nervous system (CNS) radiotherapy: radiation of 60 gray (Gy) in 30 fractions, 59.4 Gy in 1.8 Gy fractions, 75 Gy in 30 fractions or equivalent or lower doses
• Minimum interval since last major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy, or significant traumatic injury is 4 weeks prior to registration; minimum interval since minor procedures, percutaneous biopsies or placement of vascular access device is 1 week prior to registration; patients must have recovered from side effects of such procedure or injury prior to registration
• Minimum interval since last investigational agent and/or prior cytotoxic drug therapy (patient must have also recovered from the toxic effects of any prior therapy): * 3 weeks since last non-cytotoxic therapy * 3 weeks must have elapsed since the completion of a non-nitrosourea-containing chemotherapy regimen * 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen
• Patients must have signed an approved informed consent
• Patients with the potential for pregnancy or impregnating their partner must agree to practice effective contraceptive methods to avoid conception while on study and for 6 months after study completion
• Female patients of child-bearing potential must have a negative pregnancy test within 14 days prior to study registration
• Patients with history of prior invasive malignancy (except non-melanomatous skin cancer and glioblastoma diagnosis) must have been disease free for a minimum of 1 year
• Patients must be maintained on a stable or decreasing corticosteroid regimen from the time of their baseline scan until registration
• Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight [LMW] heparin) must meet both of the following criteria: * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices) * In-range international normalized ratio (INR) (maximum [max] =< 3) on a stable dose of oral anticoagulant for greater than 1 month or on a stable dose of low molecular weight heparin

Exclusion Criteria

• Greater than two cycles of bevacizumab or any prior therapy with an inhibitor of vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR)
• Any significant CNS hemorrhage defined as > 1 cm diameter of blood seen on the pre-registration brain MRI with contrast scan; if > 1 cm of acute blood is detected, the patient will be ineligible for this trial
• Patients with impaired cardiac function or clinically significant cardiac diseases, including any of the following: * History or presence of serious uncontrolled ventricular or significant arrhythmias * Any of the following within 6 months prior to registration: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA), pulmonary embolism (PE) * Uncontrolled hypertension (defined by a systolic blood pressure [SBP] >= 160 mmHg or diastolic blood pressure [DBP] >= 100 mmHg while on anti-hypertensive medications) or history of hypertensive crisis or hypertensive encephalopathy, stroke, TIA, symptomatic peripheral vascular disease, or grade 2 CHF
• Patients with cirrhosis, or active viral or non-viral hepatitis
• Patients with peptic ulcer, abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within 6 months of registration
• Patients with active implanted medical or electronic device or bullet fragments including pacemakers, defibrillators, deep brain stimulators, spinal cord stimulators, vagus nerve stimulators, and programmable shunts
• Infratentorial, leptomeningeal, or multifocal tumor
• Known sensitivity or allergy to conductive hydrogels (like the gel used on electrocardiogram [ECG] stickers or TENS [transcutaneous electrical nerve stimulation] electrodes)
• Known diagnosis of human immunodeficiency virus (HIV) infection (please note that HIV testing is not mandatory)
• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
• Pregnant or breast-feeding women
• Patients treated on any other therapeutic clinical protocols within 3 weeks of registration
• Patients with gastrointestinal bleeding or any other hemorrhage/bleeding event (Common Terminology Criteria for Adverse Events [CTCAE] version [v.]4) grade 3 or greater within 30 days prior to registration will be ineligible