Bevacizumab Beyond Progression (BBP)

Inclusion Criteria

• Patients with histologically confirmed WHO Grade IV primary malignant glioma (glioblastoma or gliosarcoma);
• Patients ≥ 18 years of age;
• An interval of at least 2 weeks, but not ≥ 8 weeks between prior surgical procedure and initiation of treatment;
• Karnofsky Performance Status (KPS) ≥ 60%
• Laboratory Values:
• Platelet Count ≥ 125,000 cells/µL
• Absolute neutrophil count (ANC) ≥ 1, 500 cells/µL
• Adequate renal function indicated by all of the following:
• Serum creatinine ≤ 1.25 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 ml/min
• Urine dipstick for proteinuria 6 months following the last administration of trial drug(s). Female patients with an intact uterus (unless amenorrhea for the last 24 months) must have a negative serum pregnancy test within 7 days prior to first study treatment.
• Fertile male patients must agree to use a highly effective contraceptive method (allowed methods of birth control [i.e. with a failure rate of 6 months following the last administration of trial drugs.

Exclusion Criteria

• Any prior treatment for any grade glioma, including, but not limited to gliadel wafers, immunotherapy (including vaccine therapy), radiation therapy or chemotherapy, irrespective of grade of the tumor (NOTE: 5-aminolevulinic acid (ALA)-mediated photodynamic therapy administered prior to surgery to aid in optimal surgical resection is not considered a chemotherapy agent.);
• Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids;
• Active infection requiring intravenous antibiotics;
• Prior or current treatment with bevacizumab or other anti-angiogenic treatment (i.e. anti-vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR) therapies or tyrosine kinase inhibitors) for any condition;
• Treatment with any other investigational agent within 28 days or 2 investigational agent half-lives (whichever is longer) prior to first study treatment;
• Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin;
• Evidence of > Grade 1 central nervous system (CNS) hemorrhage on post-operative MRI scan, unless repeat MRI or CT performed prior to initiating bevacizumab shows stable grade 1 or resolving ( 150 mmHg and/or diastolic blood pressure > 100 mmHg) within 28 days of first study treatment;
• Prior history of hypertensive crisis, hypertensive encephalopathy, reverse posterior leukoencephalopathy syndrome (RPLS);
• Prior history of gastrointestinal perforation or abscess;
• Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment;
• History or evidence upon physical/neurological examination of central nervous system disease (e.g. seizures) unrelated to cancer unless adequately controlled by medication or potentially interfering with protocol treatment;
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to start of study treatment. Any previous venous thromboembolism > NCI common toxicity criteria adverse event (CTCAE) Grade 3;
• History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as ≥ 2.5 mL bright red blood per episode) within 1 month of first study treatment;
• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation);
• Current or recent (within 10 days of study enrollment) use of aspirin (>325 mg/day), clopidogrel (>75 mg/d