Journal article

A phase i study of the oral gamma secretase inhibitor R04929097 in combination with gemcitabine in patients with advanced solid tumors (PHL-078/CTEP 8575)

S Richter, PL Bedard, EX Chen, BA Clarke, B Tran, SJ Hotte, A Stathis, HW Hirte, ARA Razak, M Reedijk, Z Chen, B Cohen, WJ Zhang, L Wang, SP Ivy, MJ Moore, AM Oza, LL Siu, E McWhirter

Investigational New Drugs | SPRINGER | Published : 2014

Abstract

Purpose To establish the recommended phase II dose of the oral γ-secretase inhibitor RO4929097 (RO) in combination with gemcitabine; secondary objectives include the evaluation of safety, tolerability, pharmacokinetics, biomarkers of Notch signaling and preliminary anti-tumor activity. Methods Patients with advanced solid tumors were enrolled in cohorts of escalating RO dose levels (DLs). Tested RO DLs were 20 mg, 30 mg, 45 mg and 90 mg. RO was administered orally, once daily on days 1-3, 8-10, 15-17, 22-24. Gemcitabine was administered at 1,000 mg/m2 on d1, 8, and 15 in 28 d cycles. Dose limiting toxicities (DLTs) were assessed by CTCAE v4. Serial plasma was collected for RO (total and unbo..

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University of Melbourne Researchers

Grants

Awarded by National Cancer Institute


Funding Acknowledgements

This study (PHL-078/CTEP 8575) is conducted by the Princess Margaret Hospital Phase I Consortium with support from the US National Cancer Institute U01 Cooperative Agreement Award (U01-CA132123)