NovoTTF-100A With Bevacizumab and Carmustine in Treating Patients With Glioblastoma Multiforme in First Relapse

PRIMARY OBJECTIVES:

I. Establish the safety of NovoTTF-100A in combination with bevacizumab and BCNU (carmustine)
in glioblastoma multiforme (GBM) patients who have relapsed after chemoradiation therapy
(first relapse).

II. Determine the 6 month overall survival (OS). III. Determine the 6 month progression free
survival (PFS). IV. Evaluate the effect of this therapy regimen on quality-of-life.

OUTLINE:

Patients receive bevacizumab intravenously (IV) over 30-90 minutes every 2 weeks beginning on
day -7 for up to 13 doses and carmustine IV over 4 hours every 8 weeks beginning on day 1 for
up to 3 doses. Patients also undergo NovoTTF-100A according to standard procedures starting
one week before the first dose of carmustine.

After completion of study treatment, patients are followed up for 12 months.

Inclusion Criteria:

- Histologically confirmed GBM

- Progressive disease after temozolomide and radiation therapy (in "first relapse")

- At least 28 days since chemotherapy or radiation

- Karnofsky performance score at least 70%

- Platelet count >= 130/mm^3

- Absolute neutrophil count >= 1500/mm^3

- Calculated creatinine clearance greater than 45 mg/dl using the Cockcroft-Gault
formula

- Aspartate aminotransferase (AST) < 2 times the upper limit of normal

- Bilirubin < 1.5 times the upper limit of normal

- Subjects with child-bearing potential agree to use effective means of contraception

Exclusion Criteria:

- Prior systemically administered nitrosoureas or vascular endothelial growth factor
(VEGF) targeted therapy

- Chemotherapy for glioma other than temozolomide or Gliadel wafers (steroids are
allowed)

- Pregnant or breast feeding

- Active inflammatory bowel disease

- Abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess
within 6 months

- Hypertension: systolic blood pressure (SBP) > 150 or diastolic blood pressure (DBP) >
100 mm mercury (Hg) despite antihypertensive medications

- New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF);
myocardial infarction or unstable angina within 6 months

- History of thrombosis

- Symptomatic peripheral vascular disease, stroke or transient ischemic attack within 6
months

- Bleeding risks: Required to be on therapeutic anticoagulation (aspirin is allowed),
coagulopathy (e.g. hemophilia or von Willebrand's disease); any grade III or greater
hemorrhage, major surgical procedure, or significant trauma within 28 days; core
biopsy or other minor surgical procedure, excluding placement of a vascular access
device, within 7 days

- Activated partial thromboplastin time (APTT) must not exceed 32.5 seconds (normal
range 21.8-31.5 seconds); international normalized ratio (INR) must not exceed 1.30
(normal range 0.87-1.18)

- Serious, non-healing wound, ulcer, or bone fracture

- Active implanted medical device (e.g. deep brain stimulators, spinal cord stimulators,
vagus nerve stimulators, pacemakers, defibrillators, and programmable shunts), a skull
defect (such as missing bone with no replacement), a shunt, or bullet fragments

- Known sensitivity to conductive hydrogels like the gel used on electrocardiogram (ECG)
stickers or transcutaneous electrical nerve stimulation (TENS) electrodes

- Human immunodeficiency virus (HIV) positive

- Proteinuria at screening as demonstrated by urine dipstick >= 2+

- Prior organ transplantation

- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), clopidogrel or any other drug
whose goal is to inhibit platelet function

- Unable to give signed informed consent