Primary Objective To estimate 6-month progression free survival probability of patients with
recurrent glioblastoma multiforme treated with bortezomib plus Avastin. This efficacy
assessment will be made separately among patients on enzyme-inducing anti-epileptic drugs
and non enzyme-inducing anti-epileptic drugs.
Secondary Objectives To evaluate safety & tolerability of bortezomib plus Avastin among
patients with recurrent malignant glioma.
To evaluate radiographic response, progression free survival & overall survival of patients
with recurrent malignant glioma treated with bortezomib plus Avastin
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
