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01-01-2018 | Clinical Study

Phase I study of sorafenib and tipifarnib for recurrent glioblastoma: NABTC 05-02

Authors: Phioanh Leia Nghiemphu, Victoria Asuquo Ebiana, Patrick Wen, Mark Gilbert, Lauren E. Abrey, F. Lieberman, Lisa M. DeAngelis, H. Ian Robins, W. K. Alfred Yung, Susan Chang, Jan Drappatz, Minesh P. Mehta, Victor A. Levin, Kenneth Aldape, Janet E. Dancey, J. J. Wright, Michael Prados, John Kuhn, Timothy F. Cloughesy

Published in: Journal of Neuro-Oncology | Issue 1/2018

Abstract

Recurrent glioblastoma (GBM) has a very low 6-month progression free survival (PFS) with currently available treatments. Combination chemotherapy to target multiple cell signaling pathways is currently being investigated in order to improve prognosis for recurrent disease. The purpose of this phase I study was to determine the maximum tolerated dose (MTD) for the combination of tipifarnib and sorafenib for the treatment of recurrent GBM. Patients with pathologically proven WHO grade IV GBM and radiographically proven tumor recurrence were eligible for this study. Treatments included sorafenib at twice daily and escalating dosages of tipifarnib. Dose-limiting toxicity (DLT) was determined over the first 28-days of treatments, and the MTD was determined in a 3 + 3 study design. We enrolled 24 patients, and 21 patients completed the MTD period. The study was stopped early with no MTD determination for excessive toxicities. The last dose level reached was sorafenib at 200 mg twice a day and tipifarnib 100 mg twice a day on an alternating week schedule. The DLTs included diarrhea, lipase elevation, hypophosphatemia, and arthralgia. The combination of sorafenib and tipifarnib has excessive toxicities and full single agent dosages could not be achieved in combination.

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Title: Phase I study of sorafenib and tipifarnib for recurrent glioblastoma: NABTC 05-02
Authors: Phioanh Leia Nghiemphu
Victoria Asuquo Ebiana
Patrick Wen
Mark Gilbert
Lauren E. Abrey
F. Lieberman
Lisa M. DeAngelis
H. Ian Robins
W. K. Alfred Yung
Susan Chang
Jan Drappatz
Minesh P. Mehta
Victor A. Levin
Kenneth Aldape
Janet E. Dancey
J. J. Wright
Michael Prados
John Kuhn
Timothy F. Cloughesy
Publication date: 01-01-2018
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2018
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-017-2624-4

At a glance: The STEP trials

Springer Medicine

Phase I study of sorafenib and tipifarnib for recurrent glioblastoma: NABTC 05-02

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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