Phase 1/2 Dose-Escalation Study of TPI 287 in Combination With Bevacizumab Followed by Randomized Study of the Maximum Tolerated Dose of TPI 287 in Combination With Bevacizumab Versus Bevacizumab Alone in Adults With Recurrent Glioblastoma
This trial is divided into two parts, a dose-escalation study (phase 1) and a randomized study (phase 2). The purpose of the dose-escalation study (phase 1) is to determine the safety, maximum tolerated dose (MTD), and efficacy of TPI 287 in combination with Avastin (bevacizumab) in subjects who have glioblastoma multiforme (GBM) that has progressed following prior radiation therapy and temozolomide (TMZ). The purpose of the randomized study (phase 2) is to determine the safety and efficacy of the phase 1 MTD of TPI 287 in combination with bevacizumab versus bevacizumab alone in subjects who have GBM that has progressed following prior radiation therapy and TMZ.
• Histologically proven GBM
• Disease progression following radiation and TMZ
• Up to 2 prior relapses allowed
• Baseline MRI within 17 days of Day 1 \& on steroid dosage that has been stable or decreasing for at least 5 days
• Recent resection of recurrent or progressive tumor allowed as long as at least 4 weeks have elapsed from date of surgery and the subject has recovered from surgery
• Life expectancy \>12 weeks
• Eighteen years old or older
• KPS equal to or greater than 70
• Recovered from toxic effects of prior therapy to \< Grade 2 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) prior to Day 1. Minimum duration required between prior therapy and Day 1 is:
∙ 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
‣ 4 weeks from prior cytotoxic therapy
‣ 4 weeks from prior experimental drug
‣ 6 weeks from nitrosoureas
‣ 3 weeks from procarbazine
‣ 1 week for non-cytotoxic agents, such as interferon, tamoxifen, \& cis-retinoic acid
⁃ Adequate bone marrow function (absolute neutrophil count \> 1,500/mm3 and platelet count of \> 100,000/mm3), adequate liver function \[ALT and AST \<3 x upper limit normal (ULN), alkaline phosphatase \<2 x ULN, and total bilirubin \<1.5 mg/dL\], \& adequate renal function (BUN and creatinine \<1.5 x ULN)
⁃ Minimum hemoglobin of 9 g/dL
⁃ Males \& women of childbearing potential must agree to abstain from sex or use an adequate method of contraception for the duration of study, \& for 6 months after last dose of study drug
⁃ Signed \& dated informed consent prior to Screening evaluations