Phase I open-label study of cediranib, an oral inhibitor of VEGF signalling, in combination with the oral Src inhibitor saracatinib in patients with advanced solid tumours
- 12 October 2011
- journal article
- Published by Springer Science and Business Media LLC in Investigational New Drugs
- Vol. 30 (5), 1962-1971
- https://doi.org/10.1007/s10637-011-9754-x
Abstract
Combining different targeted anticancer agents may improve clinical outcomes. This Phase I study investigated cediranib, an oral inhibitor of vascular endothelial growth factor signalling in combination with saracatinib, an oral Src inhibitor. The primary endpoint was safety/tolerability. Secondary assessments included pharmacokinetics and preliminary efficacy. Patients and Methods Patients with advanced solid tumours received cediranib 20, 30 or 45 mg/day for 7 days followed by daily treatment with cediranib at the same dose plus saracatinib 175 mg/day. Results Thirty-nine patients received cediranib (20 mg, n = 6; 30 mg, n = 6; 45 mg, n = 27 [n = 20 in cohort expansion]) plus saracatinib. In the cediranib 45 mg cohort, 59% of patients required dose reduction/pause compared with 33% in each of the other two cohorts. There was one dose-limiting toxicity (hypertension; 45 mg cohort). The most common adverse events were hypertension (67%), diarrhoea (62%), dysphonia (46%) and fatigue (39%). There was no evidence of a clinically significant effect of saracatinib on cediranib pharmacokinetics and vice versa. 22/35 evaluable patients had a best response of stable disease. Conclusions All cediranib doses were tolerated; however, in patients with advanced solid tumours, for combination with saracatinib 175 mg/day, cediranib 20 or 30 mg/day was more sustainable than 45 mg/day.Keywords
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