Phase II Avastin + Bortezomib for Patients With Recurrent Malignant Glioma

Inclusion Criteria:

Patients have histologically confirmed diagnosis of recurrent/progressive WHO grade IV 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
• KPS > or equal to 70%
• Hgb > or = to 9 g/dL, ANC > or = to 1,500 cells/microliter, platelets > or = to 125,000 cells/microliter;
• Serum creatinine <1.5 mg/dl, serum 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 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 PT, 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