
    due to lack of clinical benefit in the 17 subjects enrolled in the trial to date
  
['glioblastoma multiforme']
['tpi 287', 'bevacizumab']

        Inclusion Criteria:

          1. Histologically proven GBM

          2. Disease progression following radiation & TMZ

          3. 1st progression of GBM on bevacizumab-containing regimen or within 8 weeks of
             discontinuing bevacizumab. In either case, must have received a minimum of 8 weeks (4
             infusions) of bevacizumab.

          4. Baseline MRI must be performed after subject signs informed consent form (ICF), within
             17 days of Day 1, & on steroid dosage that has been stable or decreasing for at least
             5 days

          5. Recent resection of recurrent or progressive tumor allowed as long as at least 4 weeks
             have elapsed from date of surgery & subject has recovered from surgery

          6. Life expectancy >12 weeks

          7. Eighteen years old or older

          8. KPS equal to or greater than 70

          9. Recovered from toxic effects of prior therapy to < Grade 2 toxicity per National
             Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) prior to
             Day 1. Minimum duration required between prior therapy & Day 1 is:

               1. At least 12 weeks from completion of radiation therapy except if there is
                  unequivocal evidence for tumor recurrence in which case at least 4 weeks

               2. 4 weeks from prior cytotoxic therapy

               3. 4 weeks from prior experimental drug

               4. 6 weeks from nitrosoureas

               5. 3 weeks from procarbazine

               6. 1 week for non-cytotoxic agents (e.g., interferon, tamoxifen, & cis-retinoic
                  acid)

               7. 14 days from last dose of bevacizumab

         10. Adequate bone marrow function [absolute neutrophil count (ANC) > 1,500/mm3 & platelet
             count of > 100,000/mm3], adequate liver function [alanine aminotransferase (ALT) &
             aspartate aminotransferase (AST) <3 x upper limit normal (ULN), alkaline phosphatase
             <2 x ULN, & total bilirubin <1.5 mg/dL], & adequate renal function (BUN & creatinine
             <1.5 x ULN)

         11. Minimum hemoglobin of 9 g/dL

         12. Males & women of childbearing potential must agree to abstain from sex or use an
             adequate method of contraception for duration of study & for 6 months after last dose
             of study drug

         13. Signed & dated ICF prior to Screening evaluations

        Exclusion Criteria:

          1. Radiographic evidence of contrast-enhancing tumor crossing midline, leptomeningeal
             dissemination, gliomatosis cerebri or infratentorial tumor

          2. Evidence or suspicion of disease metastatic to sites remote from supratentorial brain

          3. Prior treatment with anti-vascular endothelial growth factor (VEGF) drugs other than
             bevacizumab

          4. Prior treatment with tyrosine-kinase inhibitors targeting VEGF, platelet-derived
             growth factor, fibroblast growth factor, tyrosine kinase with immunoglobulin-like and
             epidermal growth factor-like domains 2 (TIE-2), or angiopoietin (or their receptors)

          5. Prior treatment with histone deacetylase inhibitors or mammalian target of rapamycin
             (mTOR) inhibitors

          6. Prior treatment with TPI 287

          7. Treatment with Enzyme-Inducing Anti-Epileptic Drugs within 2 weeks prior to Day 1

          8. Treatment with drugs or herbal supplements known to be strong inhibitors/inducers of
             cytochrome P450 3A4 or 2C8 within 2 weeks prior to Day 1

          9. Received more than one course of radiation therapy or more than a total dose of 65 Gy.
             May have received radiosurgery as part of initial therapy; however, dose counts
             against total dose limit.

         10. Prior taxane, vincristine, or other microtubule inhibitor chemotherapies for treatment
             of GBM or other malignancy

         11. 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 course of
             study

         12. Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to Day 1

         13. Any condition, including the presence of clinically significant laboratory
             abnormalities, which places subject at unacceptable risk if he/she were to participate
             in study or confounds the ability to interpret data from study, including:

               1. Active infection including known AIDS or Hepatitis C or with a fever ≥38.5°C
                  within 3 days prior to study enrollment

               2. Diseases or conditions that obscure toxicity or dangerously alter drug metabolism

               3. Serious intercurrent medical illness (e.g., symptomatic congestive heart failure)

         14. Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent subject from providing informed consent

         15. Inadequately controlled hypertension (defined as systolic blood pressure >140 mmHg
             and/or diastolic blood pressure > 90 mmHg)

         16. Prior history of hypertensive crisis or hypertensive encephalopathy

         17. New York Heart Association Grade II or greater congestive heart failure

         18. History of myocardial infarction or unstable angina within 6 months prior to Day 1

         19. History of stroke or transient ischemic attack within 6 months prior to Day 1

         20. Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
             recent peripheral arterial thrombosis) within 6 months prior to Day 1

         21. History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month
             prior to Day 1

         22. Evidence of bleeding diathesis or significant coagulopathy (in absence of therapeutic
             anticoagulation)

         23. Grade 2 or higher peripheral neuropathy per NCI CTCAE

         24. History of abdominal fistula or gastrointestinal perforation within 6 months prior to
             Day 1

         25. Serious, non-healing wound, active ulcer, or untreated bone fracture

         26. Proteinuria at Screening. Subjects with a urine dipstick protein ≥ 2+ at Screening
             will undergo a 24-hour urine collection and must demonstrate ≤ 1g of protein in 24
             hours to be eligible.

         27. Known hypersensitivity to any inactive ingredient of bevacizumab

         28. Known hypersensitivity to any inactive ingredient of TPI 287

         29. Pregnancy (positive pregnancy test) or lactation

         30. Inability to comply with protocol or study procedures

         31. Previously or currently enrolled in Protocol No. TPI-287-17
      