Atct-15cb-018: a Phase 2 Trial of Bevacizumab Plus Tpi 287, a Novel Brain Penetrable Anti-microtubule Agent, in Patients With Recurrent Glioblastoma Following Progression on Anti-angiogenic Therapy
Year: 2015
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND: There is a significant unmet need for effective therapy for recurrent glioblastoma (GBM). TPI 287, a third-generation taxane that readily penetrates the blood brain barrier, is currently under investigation for the treatment of recurrent GBM in patients with and without prior exposure to bevacizumab (BEV). Here we report initial results from CB-018, a dose escalation multi-center trial designed to determine the maximum tolerated dose (MTD) and efficacy of TPI 287 in combination with BEV in patients that experienced disease progression on a prior BEV-containing regimen. METHODS: Patients with recurrent GBM following first relapse on a BEV-containing regimen are eligible for enrollment. BEV is administered at 10 mg/kg as an IV infusion once every 2 weeks. TPI 287 is administered as a 1-hour IV infusion every 3 weeks. Dose escalation of TPI 287 is planned until a dose-limiting toxicity (DLT) is observed, at which point additional patients will be enrolled to confirm the MTD. MRIs are obtained at the end of every six-week cycle with response assessment via RANO. RESULTS: As of June 2015, 13 patients have been enrolled in 3 dose-escalation cohorts (140, 160, and 170 mg/sq m of TPI 287). Among 8 patients evaluable for response, there has been one responder (CR) and 3 patients with stable disease. The combination regimen has been well-tolerated and no DLTs have been observed to date. Dose escalation continues. CONCLUSIONS: TPI 287 is safe and potentially efficacious in combination with bevacizumab for the treatment of BEV-refractory recurrent GBM. Updated safety and efficacy results will be presented.
Source: Neuro-Oncology
Authors: Samuel Goldlust, L. Burt Nabors, Solmaz Sahebjam, Sigmund Hsu, Nimish Mohile, Tara Benkers, Pierre Giglio, Jeffrey Raizer, Sandra Silberman, Priya Kumthekar, Samuel Singer, George Farmer
Institutions: Hackensack University Medical Center, University of Alabama at Birmingham, Moffitt Cancer Center, The University of Texas Health Science Center at Houston, University of Rochester, Swedish Medical Center, The Ohio State University, Northwestern University, Cortice Biosciences, Inc. (United States)
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2339960722