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

Status: Suspended
Location: See all (9) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No
View:

• 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

Locations
United States
Alabama
University of Alabama at Birmingham
Birmingham
Missouri
Washington University School of Medicine
Saint Louis
New Jersey
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack
New York
The Long Island Brain Tumor Center at Neurological Surgery, P.C.
Commack
The Long Island Brain Tumor Center at Neurological Surgery, P.C.
Lake Success
University of Rochester Medical Center
Rochester
Ohio
The Ohio State University Wexner Medical Center
Columbus
Texas
Memorial Hermann Hospital
Houston
Washington
Swedish Neuroscience Institute
Seattle
Time Frame
Start Date: August 2013
Completion Date: May 2023
Participants
Target number of participants: 92
Treatments
Experimental: TPI 287 + bevacizumab
All subjects in phase 1 & subjects randomized to the TPI 287 + bevacizumab arm in phase 2 will be administered a 1-hour IV infusion of TPI 287 once every 3 weeks (Days 1 & 22 of 42-day cycle) & a 30-90 minute IV infusion of bevacizumab once every 2 weeks (Days 1, 15, & 29).~In phase 1, the dose of TPI 287 will be escalated in sequential dose cohorts of 3 to 6, while the dose of bevacizumab remains constant (10 mg/kg). The first 5 dose levels will be 140, 150, 160, 170, & 180 mg/m2. Dose levels beyond 180 mg/m2 will be increased in increments of 20 mg/m2. Three subjects will be treated at a dose level halfway between the dose level that exceeds the MTD and the dose level immediately prior to further refine the MTD.~In phase 2, the dose of TPI 287 will be the MTD determined in phase 1, & the dose of bevacizumab will be the same as phase 1 (10 mg/kg).~Subjects may continue on treatment unless they meet one or more of the protocol discontinuation criteria.
Active Comparator: Bevacizumab
All subjects randomized to the bevacizumab alone arm in phase 2 will be administered bevacizumab as a 30 to 90 minute IV infusion once every 2 weeks (Days 1, 15, and 29 of a 42-day cycle). The dose of bevacizumab will be 10 mg/kg.~Subjects will be withdrawn from the study if they meet one or more of the discontinuation criteria outlined in the protocol; however, treatment with bevacizumab may continue under the FDA approved labeling for bevacizumab at the discretion of the subject's doctor.~All subjects in phase 1 will be administered TPI 287 in combination with bevacizumab (i.e., there will be no bevacizumab alone arm during phase 1).
Authors
Samuel A. Goldlust, Sigmund Hsu, Nimish Mohile, Jian Campian, Pierre Giglio, Tara L. Benkers, Louis B. Nabors, J. P. Duic
Sponsors
Leads: Cortice Biosciences, Inc.

This content was sourced from clinicaltrials.gov

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