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).

Suzanne Richter, Philippe L Bedard, Eric Xueyu Chen, Blaise A Clarke, Ben Tran, Sebastien J Hotte, Anastasios Stathis, Hal W Hirte, Albiruni RA Razak, Michael Reedijk, Zhuo Chen, Brenda Cohen, Wen-Jiang Zhang, Lisa Wang, S Percy Ivy, Malcolm J Moore, Amit M Oza, Lillian L Siu, Elaine McWhirter

Investigational New Drugs | Published : 2014


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/m(2) 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 ..

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