Trial of Temozolomide, Bevacizumab Plus Bortezomib for Recurrent Glioblastoma Multiforme

Exclusion Criteria

• •1. Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.
• •2. Greater than three prior recurrences.
• •3. Enzyme-inducing anti-epileptic drugs (EIAEDs) of the CYP-450 such as phenytoin, carbamazepine, phenobarbital.
• •4. Patients receiving concurrent investigational drugs.
• •5. Evidence of central nervous system (CNS) hemorrhage on baseline MRI or CT scan (except for grade 1 hemorrhage that has been stable for at least 3 months).
• •6. History of stroke within six months.
• •7. Requires therapeutic anti-coagulation.
• •8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics and psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state.
• •9. Patient has a calculated or measured creatinine clearance of \< 20 mL/minute within 14 days prior to treatment initiation.
• •10. Patient has greater or equal to Grade 2 peripheral neuropathy within 14 days before enrollment.
• •11. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (Appendix), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
• •12. Patient has hypersensitivity to bortezomib, boron, or mannitol.
• •13. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• •14. Patient has received other investigational drugs within 14 days of treatment initiation
• •15. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• •16. Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy. Patients with prior malignancies must be disease free for at least 5 years.
• •17. Serious, non-healing wound, active ulcer, or untreated bone fracture. Bone fractures must be healed.