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Clinical Trial
. 2018 Jan;136(1):79-86.
doi: 10.1007/s11060-017-2624-4. Epub 2017 Oct 7.

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

Phioanh Leia Nghiemphu  1 , Victoria Asuquo Ebiana  2   3 , Patrick Wen  4 , Mark Gilbert  5 , Lauren E Abrey  6 , F Lieberman  7 , Lisa M DeAngelis  6 , H Ian Robins  8 , W K Alfred Yung  9 , Susan Chang  10 , Jan Drappatz  7 , Minesh P Mehta  11 , Victor A Levin  9 , Kenneth Aldape  12 , Janet E Dancey  13 , J J Wright  5 , Michael Prados  10 , John Kuhn  14 , Timothy F Cloughesy  2
Affiliations
Clinical Trial

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

Phioanh Leia Nghiemphu et al. J Neurooncol. 2018 Jan.

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.

Keywords: Combination study; Recurrent GBM; Sorafenib; Tipifarnib.

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Conflict of interest statement

Conflict of interest: Dr. Chang is a consultant to Edge and Blaze and serves as research support to Route and Novartis. Dr. Dancey receives funding from AstraZeneca, Pfizer, and Merck for her institution. Dr. Wen provides research support to Agios, Angiochem, AstraZeneca, Genentech, Roche, Glaxosmith Kline, Immunocellular Therapeutics, Karyopharm, Merck, Novartis, Oncoceotics, Sanofi-Aventis. Dr. Wen serves on the advisory board for AstraZeneca, Cavion, Genentech/Roche, Insys, Monteris, Novogen, Novartis, Regeneron Vascular Biogenics, VBI Vaccines. Dr. Wen is a speaker for Merck and serves on the Data Monitoring Safety Board for Tocagen and Monteris. Dr. DeAngelis serves on the scientific advisory boards of Sapience, Roche, and Tocagen.

Figures

Fig. 1
Fig. 1
Inhibition in the RAS-MAPK pathway by tipifarnib and sorafenib
See this image and copyright information in PMC

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References

    1. American Cancer Society. Cancer Facts & Figures 2010. American Cancer Society; Atlanta: 2010.
    1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO the European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups and the National Cancer Institute of Canada Clinical Trials G. Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. New England Journal of Medicine. 2005;352(10):987–996. doi: 10.1056/NEJMoa043330. - DOI - PubMed
    1. Wong E, Hess K, Gleason M, Jaeckle K, APK, MDP, VAL, WKY Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. Journal of Clinical Oncology. 1999;17(8):2572. - PubMed
    1. Lamborn KR, Yung WKA, Chang SM, Wen PY, Cloughesy TF, DeAngelis LM, Robins HI, Lieberman FS, Fine HA, Fink KL, Junck L, Abrey L, Gilbert MR, Mehta M, Kuhn JG, Aldape KD, Hibberts J, Peterson PM, Prados MD North American Brain Tumor C. Progression-free survival: An important end point in evaluating therapy for recurrent high-grade gliomas. Neuro-Oncology. 2008;10(2):162–170. doi: 10.1215/15228517-2007-062. - DOI - PMC - PubMed
    1. Friedman HS, Prados M, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. Journal of Clinical Oncology. 2009;27(28):4733–4740. - PubMed

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