Phase I/II Bevacizumab Versus Bevacizumab Plus TPI 287 for Recurrent Glioblastoma

Inclusion Criteria: 1. Patients must have histologically proven glioblastoma or gliosarcoma to be eligible for this protocol. Patients will be eligible if the original histology was low-grade glioma or anaplastic glioma (WHO II or III) and a subsequent histological diagnosis of glioblastoma or gliosarcoma is made. Only patients with histologically proven or imaging proven recurrent glioblastoma or gliosarcoma will be eligible for this protocol. 2. Patients must have shown unequivocal evidence for tumor recurrence or progression by MRI scan and should have failed radiation and temozolomide therapy. The scan done prior to study entry documenting progression will be reviewed by the treating physician to document changes in tumor dimension to confirm recurrence. Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis. 3. For this study, patients may have had up to 2 prior relapses provided the functional status and other eligibility criteria for enrollment are met. 4. All patients must sign an informed consent indicating their awareness of the investigational nature of this study in keeping with the policies of this hospital. 5. The baseline on-study MRI should be performed within 14 days (+/- 3 working days) prior to registration and on a steroid dosage that has been stable or decreasing for at least 5 days. If the steroid dose is increased between the date of imaging and the initiation of therapy (or at that time), a new baseline MRI is required. The same type of scan, i.e., MRI, must be used throughout the period of protocol treatment for tumor measurement. 6. Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: a) At least 4 weeks have elapsed from the date of surgery and the patients have recovered from the effects of surgery. b) Evaluable or measurable disease following resection of recurrent tumor is not mandated for eligibility into the study. c) To best assess the extent of residual measurable disease post-operatively, a MRI should be done no later than 96 hours in the immediate post-operative period. 7. Patients must be 18 years old or older. 8. Patients must have a Karnofsky performance status (KPS) equal or greater than 60. 9. Patients must have recovered from the toxic effects of prior therapy to \< grade 2 toxicity per CTC version 4 (except deep vein thrombosis) prior to Day 1 of Cycle 1: a) at least 12 weeks from completion of radiation therapy except if there is unequivocal evidence for tumor recurrence (such as histological confirmation or advanced imaging data such as positron emission computed tomography (PET) scan in which case at least 4 weeks from completion of radiation therapy will suffice (Note: for patients who have undergone surgery to confirm recurrence after radiation therapy, guidelines in 5.2.6a should be followed). b) 4 weeks from prior cytotoxic therapy. c) 4 weeks from prior experimental drug. d) 2 weeks from vincristine. 10. 9\) (continued) e) 6 weeks from nitrosoureas. f) 3 weeks from procarbazine administration. g) 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, cis-retinoic acid, etc. (radiosensitizer does not count). h) Patients who receive anticancer agents for non-therapeutic purposes unrelated to this study (such as presurgically for obtaining pharmacology data for the agent) will be eligible to enter the study provided they have recovered from the toxic effects of the agent if any. i) Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair. 11. Patients must have adequate bone marrow function (ANC\> 1,500/mm3 and platelet count of \> 100,000/mm3), adequate liver function (SGPT \< 3 times upper limit normal and alkaline phosphatase \< 2 times upper limit normal, total bilirubin \<1.5 mg/dl), and adequate renal function (BUN and creatinine \<1.5 times institutional normal) prior to starting therapy. 12. Male patients on treatment with TPI 287 must agree to use an adequate method of contraception for the duration of the study, and for 30 days after the last dose of study medication. Women of childbearing potential must not be pregnant (as evidenced by a negative pregnancy test prior to study entry), must not be breast-feeding and must practice adequate contraception for the duration of the study, and for 30 days after the last dose of study medication. An adequate method of contraception is one highly effective method or more than one additional methods. Highly effective methods include intrauterine device (IUD), hormonal (birth control pills, injections, implants), tubal ligation and partner's vasectomy. Additional effective methods include latex condom, diaphragm and cervical cap. 13. Patient must be able to tolerate the procedures required in this study including periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study. 14. Exploratory, Cross-Over Trial Arm: Patients with evidence of clinical or radiographic progression on the bevacizumab alone arm are eligible for cross-over into the exploratory arm of the trial if KPS is 50 or greater and all other criteria for initial enrollment in the trial are still met at time of progression. Patients will be excluded if the investigators feel the patient will not tolerate TPI 287 or if an alternative treatment approach is deemed necessary by the treating physician. Exclusion Criteria: 1. Inability to comply with protocol or study procedures. 2. Prior treatment with bevacizumab or TPI 287. 3. Patients who are receiving concurrent Enzyme-Inducing Anti-Epileptic Drugs (EIAEDs) (e.g., carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital and primidone, or who received EIAEDs within 2 weeks prior to the first dose of study drug. 4. Patients who have received more than one course of radiation therapy or more than a total dose of 65 Gy. Patients may have received radiosurgery as part of the initial therapy (i.e., in addition to one course of radiation therapy); however, the dose used for the radiosurgery counts against the total dose limit listed above. 5. Patient who have received prior taxane chemotherapy for treatment of GBM or other malignancy. GliadelTM as part of the initial therapy is permitted. Patients who have received prior biologic therapy other than bevacizumab will be eligible. 6. Any condition, including the presence of clinically significant laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. These would include: a) Active infection including known AIDS or Hepatitis C or with a fever \>/= 38.5°C within 3 days prior to the study enrollment. b) Diseases or conditions that obscure toxicity or dangerously alter drug metabolism. c) Serious intercurrent medical illness (e.g. symptomatic congestive heart failure). 7. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from providing informed consent. 8. Inadequately controlled hypertension (defined as systolic blood pressure \>140 mmHg and/or diastolic blood pressure \> 90 mmHg) 9. Prior history of hypertensive crisis or hypertensive encephalopathy 10. New York Heart Association (NYHA) Grade II or greater congestive heart failure. 11. History of myocardial infarction or unstable angina within 6 months prior to Day 1 12. History of stroke or transient ischemic attack within 6 months prior to Day1 13. Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 14. History of hemoptysis (\>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 15. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) 16. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study. 17. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1 18. History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 19. Serious, non-healing wound, active ulcer, or untreated bone fracture. 20. Proteinuria as demonstrated by: (1) Urine protein:creatinine (UPC) ratio \>/= 1.0 at screening; OR (2) Urine dipstick for proteinuria \>/= 2+ (patients discovered to have \>/= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate \</= 1g of protein in 24 hours to be eligible). 21. Known hypersensitivity to any component of bevacizumab 22. Pregnancy (positive pregnancy test) or lactation. Not able to use of effective means of contraception (men and women) in subjects of child-bearing potential. 23. Patients with Grade 2 or higher peripheral neuropathy.