ZD6474 Phase IIa Dose Finding Multicentre Study

Experimental: ZD6474 100mg

Daily dose

Droga: ZD6474 (vandetanib) 100mg

once daily oral dose

Otros nombres:

• ZACTIMA®

Experimental: ZD6474 200mg

daily dose

Droga: ZD6474 (vandetanib) 200mg

once daily oral dose

Otros nombres:

• ZACTIMA

Experimental: ZD6474 300mg

daily dose

Droga: ZD6474 (vandetanib) 300mg

once daily oral dose

Otros nombres:

• ZACTIMA

To assess the objective response rates (by RECIST) to ZD6474 100, 200 and 300 mg/day respectively

To assess the tolerability, safety, disease control rate, duration of response, time to progression, changes in quality of life and tumour-related and overall symptom improvements, and to characterise the PK and PK-PD relationship

Tumour assessments to evaluate disease control rate, duration of response, time to progression will be performed every 4 weeks for the first 24 weeks of treatment, then every 8 weeks until PD is determined or withdrawal due to any reasons other than PD. If PR or CR is observed, tumour assessment will be repeated 4 weeks after for confirmation of the response. Quality of life questionnaire - FACT-L will be given to subjects at baseline and at 4-week intervals during the study treatment (up to Week 12). Lung cancer subscale (LCS) for disease-related symptoms collection will be completed weekly (up to Week 12). Safety and tolerability will be assessed on the ongoing basis by AZ collection, and at the site visits by vital sign, ECG and lab assessments. Blood sampling for pharmacokinetics will be performed on day 8, 15, 22, 29, 57 and 85. In the event of QTc prolongation, PK sampling will continue with the additional ECG monitoring performed until the QTc has fallen below 460 msec.