A randomized open-label phase I study to assess the effect of vandetanib on vascular permeability in patients with advanced colorectal cancer and liver metastases

4113 Background: Vandetanib is a once-daily oral inhibitor of VEGFR-2, VEGFR-3, EGFR and RET tyrosine kinases. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to assess the effects of vandetanib on tumor perfusion and vascular permeability in patients with advanced colorectal cancer (CRC) and liver metastases. Methods: Eligible patients received vandetanib 100 or 300 mg/day. DCE-MRI (iAUC60 and Ktrans) was used to quantify the primary endpoints of tumor perfusion and vascular permeability. An exploratory assessment of tumor oxygenation was performed using MRI/T2*. All MRI parameters were measured at baseline (twice) and on days 2, 8, 29 and 57. Secondary assessments were pharmacokinetics (PK), safety and tolerability, and a preliminary evaluation of efficacy. Results: Twenty-two patients received vandetanib (n=10, 100 mg; n=12, 300 mg). Baseline measurements of iAUC60 and Ktrans were reproducible, with low intrapatient coefficients of variation (11% and 24%, respectively). Changes ...