Safety & Efficacy Study of TPI 287 + Avastin in Adults With Glioblastoma That Progressed Following Prior Avastin Therapy
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|ClinicalTrials.gov Identifier: NCT02047214|
Recruitment Status : Terminated (Due to lack of clinical benefit in the 17 subjects enrolled in the trial to date)
First Posted : January 28, 2014
Last Update Posted : January 31, 2018
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Multiforme||Drug: TPI 287 Drug: Bevacizumab||Phase 2|
This multi-center trial is a phase 2, dose-escalation study of the safety, tolerability (MTD), and efficacy of TPI 287 in combination with bevacizumab in subjects who have GBM that has progressed following prior radiation and TMZ therapy and that has progressed following prior bevacizumab therapy.
All subjects will be administered TPI 287 as an intravenous (IV) infusion (target duration of 1 hour) once every 3 weeks (Days 1 and 22 of a 42-day cycle) and bevacizumab as a 30 to 90 minute IV infusion once every 2 weeks (Days 1, 15, and 29 of the 42-day cycle). The subsequent cycle will start 3 weeks after the last TPI 287 infusion and 2 weeks after the last bevacizumab infusion, maintaining the once every 3 week and once every 2 week schedule, respectively.
The dose of TPI 287 will be escalated in sequential dose cohorts of 3 to 6 subjects, while the dose of bevacizumab remains constant (10 mg/kg). The initial cohort of 3 subjects will be treated at a TPI 287 dose of 140 mg/m2 (dose level 0). The next dose level will be 160 mg/m2 (dose level 1). Subsequent dose levels will be increased in increments of 10 mg/m2 (i.e., dose level 2 = 170 mg/m2, dose level 3 = 180 mg/m2, etc.). If dose de-escalation below the starting dose level is required, dose levels of 130 and 120 mg/m2 will be used. Twelve (12) to 18 subjects are planned for enrollment during the dose escalation phase, depending on the number of subjects that experience dose limiting toxicities (DLTs).
Once the MTD is identified, 6 additional subjects will be enrolled at the MTD (for a total of 12) to better characterize the toxicity profile at this level.
Dose modifications and delays will be required as described in the protocol. Subjects may continue on treatment unless they meet one or more of the discontinuation criteria outlined in the protocol. Subjects who are discontinued prior to completing Cycle 1 for any reason other than toxicity will be replaced.
Adverse events (AEs) and concomitant medications will be monitored throughout the study. Subjects will be given a diary to record any AEs or concomitant medications taken between visits. Additional safety evaluations will include physical examination (including neurologic examination), Karnofsky performance status (KPS), weight (body surface area, BSA), vital signs, hematology, serum chemistry, and urinalysis.
Efficacy evaluations will include magnetic resonance imaging [MRI, including both pre and post-gadolinium T1-weighted scans and T2/fluid attenuated inversion recovery (FLAIR) images], corticosteroid usage, and neurologic status (as measured by neurologic exam and KPS).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||17 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 2 Dose-Escalation Study of TPI 287 in Combination With Bevacizumab in Adults With Recurrent or Progressive Glioblastoma Following a Bevacizumab-Containing Regimen|
|Study Start Date :||January 2014|
|Actual Primary Completion Date :||December 2015|
|Actual Study Completion Date :||December 2015|
Experimental: TPI 287 + bevacizumab
All subjects will be administered TPI 287 as an IV infusion (1-hour target duration) once every 3 weeks (Days 1 and 22) and 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 TPI 287 will be escalated in sequential dose cohorts of 3 to 6 subjects, while the dose of bevacizumab remains constant (10 mg/kg). The planned dose escalation levels are 140, 160, 170, and 180 mg/m2; subsequent dose levels will be increased in increments of 10 mg/m2. If dose de-escalation below the starting dose level of 140 mg/m2 is required, dose levels of 130 and 120 mg/m2 will be used. Once the MTD is identified, 6 additional subjects will be enrolled at the MTD to better characterize the toxicity profile at this level. Subjects may continue on treatment unless they meet one or more of the discontinuation criteria outlined in the protocol.
Drug: TPI 287
TPI 287 is a microtubule inhibitor belonging to the taxane diterpenoid (taxoid) family, and specifically to the abeotaxane class. TPI 287 is an Investigational Drug.
Avastin (bevacizumab) is an FDA approved drug indicated for multiple cancers, including as a single agent for GBM for adult patients with progressive disease following prior therapy. Single agent effectiveness is based on improvement in objective response rate; no data is available demonstrating improvement in disease-related symptoms or survival with bevacizumab.
Other Name: Avastin
- Safety of TPI 287 + bevacizumab in adults with GBM that progressed following radiation & TMZ & prior bevacizumab as measured by AEs, physical/neurologic exam, KPS, weight, vital signs, hematology, serum chemistry, & urinalysis [ Time Frame: Continuously over study treatment through 4 weeks after last dose of study drug ]
- MTD of TPI 287 + bevacizumab in adults with GBM that progressed following radiation & TMZ & prior bevacizumab [ Time Frame: Within 42 days of receiving the first dose of study drug ]The MTD will be defined as the highest dose level achieved at which no more than 1 out of 6 subjects experienced a DLT that initiated within 42 days of receiving the first dose of study drug.
- Efficacy of TPI 287 + bevacizumab in adults with GBM that progressed following radiation & TMZ & prior bevacizumab as measured by median progression free survival (PFS), overall response rate, & PFS rate at 4 & 6 months (PFS4 & PFS6) [ Time Frame: Baseline & on Day 1 of each 42-day treatment cycle starting with Cycle 2, and/or as clinically indicated ]The Response Assessment in Neuro-Oncology (RANO) working group recommendations for updated response criteria for high-grade gliomas (Wen et al. 2010) will be used to determine response for this trial.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02047214
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35249|
|United States, Florida|
|H Lee Moffitt Cancer Center and Research Institute, Inc.|
|Tampa, Florida, United States, 33612|
|United States, Illinois|
|Northwestern Medical Faculty Foundation|
|Chicago, Illinois, United States, 60611|
|United States, Missouri|
|Washington University, School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, New Hampshire|
|Dartmouth-Hitchcock Medical Center|
|Lebanon, New Hampshire, United States, 03756|
|United States, New Jersey|
|John Theurer Cancer Center at Hackensack University Medical Center|
|Hackensack, New Jersey, United States, 07601|
|United States, New York|
|University of Rochester Medical Center|
|Rochester, New York, United States, 14642|
|United States, Ohio|
|The Ohio State University Wexner Medical Center|
|Columbus, Ohio, United States, 43210|
|United States, Texas|
|Memorial Hermann Hospital|
|Houston, Texas, United States, 77030|
|United States, Virginia|
|University of Virginia Health System|
|Charlottesville, Virginia, United States, 22908|
|United States, Washington|
|Swedish Neuroscience Institute|
|Seattle, Washington, United States, 98122|
|Principal Investigator:||Samuel A. Goldlust, M.D.||John Theurer Cancer Center at Hackensack University Medical Center|
|Principal Investigator:||Louis B. Nabors, III, M.D.||University of Alabama at Birmingham|
|Principal Investigator:||Sigmund Hsu, M.D.||Memorial Hermann Hospital|
|Principal Investigator:||Nimish Mohile, M.D.||University of Rochester|
|Principal Investigator:||Solmaz Sahebjam, M.D.||H Lee Moffitt Cancer Center and Research Institute, Inc.|
|Principal Investigator:||Tara L. Benkers, M.D.||Swedish Neuroscience Institute|
|Principal Investigator:||Priya Kumthekar, M.D.||Northwestern University|
|Principal Investigator:||Jian Campian, M.D., Ph.D.||Washington University School of Medicine|
|Principal Investigator:||David Schiff, M.D.||University of Virginia Health System|
|Principal Investigator:||Camilo E. Fadul, M.D., F.A.A.N.||Dartmouth-Hitchcock Medical Center|
|Principal Investigator:||Pierre Giglio, M.D.||The Ohio State University Wexner Medical Center|