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

Part I and Part II of the Study: If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 3 groups of 3-6 participants will be enrolled in Part I of the study. After that, up to 90 participants will be enrolled in Part II. If you are in Part I, you will be assigned to receive 1 of 4 dose levels of TPI 287 based on when you join this study. The first 3-6 participants will receive a starting dose level. The next 3-6 participants will receive a higher dose if no intolerable side effects were seen or a lower dose if intolerable side effects were seen. Your dose may be lowered if you have side effects. All participants will receive bevacizumab at the same dose level for the entire study. If you are in Part II, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups. If you are one of the first 20 participants in Part II, you will be randomly assigned to a group. If you are enrolled after the first 20 participants, you will be more likely to be enrolled in the group that is showing better results. * If you are in Group 1, you will receive bevacizumab. * If you are in Group 2, you will receive bevacizumab and TPI 287. If the disease gets worse at any time during the treatment with bevacizumab alone, you may enroll in the Crossover Group to receive TPI 287 and bevacizumab. Other Drugs: If you are taking TPI 287, you will be given standard drugs such as Benadryl® (diphenhydramine) and cimetidine to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks. Study Drug Administration: There are 42 days in each study cycle. Part I: * On Days 1 and 22 of every cycle, you will receive TPI 287 by vein over 1 hour. * On Days 1, 15, and 29 of every cycle, you will receive bevacizumab by vein over 30-90 minutes. Part II: If you are in Group 1: ° On Days 1,15, and 29 of every cycle, you will receive bevacizumab by vein over 30-90 minutes. If you are in Group 2 or the Crossover Group: * On Days 1 and 22 of every cycle, you will receive TPI 287 by vein over 1 hour. * On Days 1, 15, and 29 of every cycle, you will receive bevacizumab by vein over 30-90 minutes. Study Visits for Part I, Group 2, or Crossover Group of Part II: Every time you receive the study drug(s), your vital signs will be recorded before and at the end of the infusion. On Days 1, 15, 22, and 29 of Cycle 1, blood (about 1- 2 teaspoons) will be collected for routine tests. On Days 1, 15, and 29 of Cycle 1, urine will be collected for kidney function tests. On Day 1 of Cycles 2 and beyond: * Your medical history and performance status will be recorded. * You will be asked about any drugs you may be taking and if you have had any side effects. * You will have a complete physical exam, including measurement of your weight. * You will have a neurological exam. * Blood (about 1-2 teaspoons) will be collected for routine tests. * Urine will be collected for kidney function tests. * You will have an MRI scan of the brain to check the status of the disease. On Days 15, 22, and 29 of Cycles 2 and beyond, blood (about 1-2 teaspoons) will be drawn for routine tests. Study Visits for Group 1 of Part II: Every time you receive the study drug(s), your vital signs will be recorded before and after the infusion. On Days 1, 15, and 29 of Cycle 1: * Blood (about 1-2 teaspoons) will be drawn for routine tests. * Urine will be collected for kidney function tests. On Day 1 of Cycle 2 and beyond: * Your medical history and performance status will be recorded. * You will be asked about any drugs you may be taking and if you have had any side effects. * You will have a complete physical exam, including measurement of your weight. * You will have a neurological exam. * Blood (about 2 teaspoons) will be collected for routine tests. * Urine will be collected for kidney function tests. * You will have an MRI scan of the brain to check the status of the disease. On Day 15 and 29 of Cycles 2 and beyond, blood (about 1-2 teaspoons) will be drawn for routine tests. At any time during the study, extra tests may be performed if the doctor thinks they are needed for your safety. The study doctor will tell you more about any extra tests. Length of Treatment: You may continue taking the study drug(s) for as long as the doctor thinks it is in your best interest. If you enroll in the Crossover Group, you may continue taking the study drugs for up to 6 additional cycles in the Crossover Group. You may no longer be able to receive the study drug(s) if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on the study will be over once you have completed the end-of-treatment and follow-up visits. End-of-Treatment Visit: Within 28 days after you stop the study drugs: * Your medical history and performance status will be recorded. * You will be asked about any drugs you may be taking and if you have had any side effects. * You will have a complete physical exam, including measurement of your weight and vital signs. * You will have a neurological exam. * Blood (about 2 teaspoons) will be collected for routine tests. * Urine will be collected for kidney function tests. * You may have an MRI scan of the brain to check the status of the disease. Long-Term Follow-Up: Every 3 months after the end-of-treatment visit for up to 1 year, you will be called and asked how you are feeling. This call will take about 5-10 minutes. This is an investigational study. TPI 287 is not FDA approved or commercially available. It is currently being used for research purposes only. Bevacizumab is FDA approved and commercially available for the treatment of brain tumors, including glioblastoma. The combination of TPI 287 and bevacizumab in glioblastoma is investigational. Up to 108 patients will take part in this study. All will be enrolled at MD Anderson.