A Phase I, Open-Label Study To Assess The Effect of ZD6474 (ZACTIMA) On Vascular Permeability In Patients with Advanced Colorectal Cancer and Liver Metastases.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Research Site
Freiberg, Germany
Assess by dynamic contrast-enhanced magnetic resonance imaging the effect of once daily dosing with ZD6474 on tumour perfusion and vascular permeability in patients with advanced colorectal cancer and liver metastases.
Time frame: Up to 57 days.
Assessment of appropriate Pharmacokinetic parameters
The exposure to ZD6474 in patients with advanced colorectal cancer and liver metastases by assessment of: maximum plasma concentration after single and at steady state (C max and Css, max); time to reach C max and Css, max (tmax); minimum plasma concentration before and at steady state (Cmin and Css, min); area under plasma concentration-time curve from zero to 24 h and at steady state (AUC(0-24) and AUCss); total body clearance of drug from plasma after an oral dose (CL/F): accumulation ratio (Rac) and fraction of ZD6474 unbound (fu).
Time frame: Predetermined timepoints after dose administration
Determine the population PK of ZD6474 and assess the relationship between both free and total plasma PK and measures of Pharmacological activity
Determination of the population PK of ZD6474 and the assessment of the relationship between both free and total plasma PK and measures of pharmacological activity by assessment of individual predicted plasma concentrations, individual predicted CL/F, AUCss, Css, max, and AUC to the point up to the scan.
Time frame: Predetermined timepoints after dose administration
Assessment of the effectiveness of ZD6474 as measured by objective response rate and progression free survival based on RECIST.
Time frame: Every 8 weeks during the study
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