Phase II Avastin + Bortezomib for Patients With Recurrent Malignant Glioma

Inclusion Criteria:

Patients have histologically confirmed diagnosis of recurrent/progressive WHO grade IV malignant glioma (MG)

* Age \>18 yrs
* No prior treatment with bortezomib, \& no Avastin in last 3 months, not allowed to have progressed to Avastin regimen. No history of \> or equal to grade 2 CNS hemorrhage or grade 3 or higher toxicities while on Avastin
* At least 6 weeks from surgical resection, 4 weeks from end of radiotherapy \& enrollment in this study
* Karnofsky Performance Status (KPS) \> or equal to 70%
* Hemoglobin (Hgb) \> or = to 9 g/deciliter (dL), absolute neutrophil count (ANC) \> or = to 1,500 cells/microliter, platelets \> or = to 125,000 cells/microliter;
* Serum creatinine \<1.5 mg/dL, serum glutamic oxalocetic transaminase (SGOT) \& bilirubin \<1.5 x upper limit of normal
* Signed informed consent approved by IRB;
* If sexually active, patients must agree to take contraceptive measures for duration of treatments
* May have had up to 3 biological therapies (such as tyrosine kinase inhibitors, topoisomerase I or II inhibitors, or rapamycin)

Exclusion Criteria:

* Gr 2 or greater peripheral neuropathy at time of study enrollment
* No prior taxanes, as it predisposes to sensory neuropathy
* Co-medication that may interfere with study results, e.g. immuno-suppressive agents other than corticosteroids
* Greater than 3 prior recurrences
* Evidence of CNS hemorrhage on baseline MRI on CT scan (except for grade 1 hemorrhage that has been stable for at least 3 months)
* History of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months
* Requires therapeutic anti-coagulation
* At least 4 weeks from Day 0 of prior monthly chemotherapy (at least 6 weeks if a nitrosourea). At least 1 week from last dose of daily chemotherapy (such as metronomic temozolomide, cytoxan) or targeted therapies administered daily (such as gleevec, tarceva)
* Pregnancy or breast feeding
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics \& psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state
* Patients with another primary malignancy that has required treatment within past year.

Avastin-Specific Concerns:

* Any prior history of hypertensive crisis or hypertensive encephalopathy
* Systolic blood pressure (BP) \> 150 mmHg or diastolic BP \> 100 mmHg
* Unstable angina
* New York Heart Association Gr II or \> congestive heart failure
* History of myocardial infarction within 6 months
* History of stroke within 6 months
* Clinically significant peripheral vascular disease
* Evidence of bleeding diathesis, coagulopathy as documented by an elevated prothrombin time (PT), partial thromboplastin time (PTT)/bleeding time
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during course of study
* Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0
* Urine protein: creatinine ratio \> or = to 1.0 at screening
* History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months prior to Day 0
* Serious, non-healing wound, ulcer, or bone fracture
* Known hypersensitivity to any component of Avastin
* Inability to comply with study and/or follow-up procedures