Efficacy and Safety Study of Vandetanib (ZD 6474) in Combination With Bicalutamide Versus Bicalutamide Alone in Patients With Chemotherapy Naive Hormone Refractory Prostate Cancer.

Patients must have a pathological diagnosis of adenocarcinoma of the prostate

Patients must have biochemically recurrent disease or metastatic disease that is asymptomatic or minimally symptomatic (total daily morphine dose \< 30mg.day) for which no curative therapy exists.

Patients must have documented evidence od PSA progression while receiving androgen ablative therapy (i.e. must be hormone refractory). Progression is defined as the development of new metastatic lesions, or rising PSA defined as at least two rises in PSA at least 1 week apart. If the second PSA is not rising, a thrid PSA is required to show further increase; if not, a subsequent level must show further increase. The third (or subsequent) PSA confirming progression must be within 2 weeks of randomization.

The PSA must be =\> 2ug/L at the time of study entry.

ECOG performance status of 0 or 1

Age =\>18 years

Patients must have a life expectancy of at least 12 weeks

No Prior chemotherapy is permissible for hormone refractory disease. Chemotherapy may have been received in a neoadjuvant or adjuvant setting provided it was given 12 months prior to registration.

Hormone Therapy

* Prior hormone therapy in the form of either medical or surgical castration is required. If the patient is receiving medical androgen abalation a castrate level of testosterone (1.7nmol/L) must be present. Therapy with LHRH agonist must continue for those prostate cancer patients already receiving this treatment at the time of registration. If the patients has discontinued the LHRH agonist, this must be restarted and a castrate level of testosterone must be present.

* Prior use of nonsteroidal antiandrogens (including bicalutamide) is permitted but must have been discontinued 6 weeks prior to registration.

Prior external beam radiation is permitted provided a minimum of 4 weeks has elapsed between the last dose and registration in the trial. Exceptions will be made for limited field, single fraction palliative radiation to bone.

No concurrent treatment with steriods unless steriods have been ingested for 4 weeks prior to commencing study at a dose of less than or equal to an equivalent of prednisone 20mg per day.

No concurrent experimental trial medication is permitted. No prior use of VEGF/VEGFR or EGFR targeting agents for hormone refractory disease is permitted.

Laboratory Requirements- within 7 calendar days prior to registration Hematology: haemoglobin \>= 100g/L neutrophils \>=1.5 x 10(9)/L Platelets \>=100 x 10(9)/L INR =\<1.5 x upper limit of normal Biochemistry: AST, ALT = \<1.5 x upperlimit of normal Bilirubin \<1.5 x upper limit of normal Serum creatinine \<1.5 x upper limit of normal

Baseline QTc (Bazett's) \<480msec determined by the average of a least 3 consecutive electrocardiograms (ECG) taken within 5-10 mins of each other.

Patient consent must be obtained according to local institutional and/or University Research and Ethic Board (REB) requirements.

Patients must be accessible for treatment and follow up.

Protocol treatment is to begin within 7 calendar days of patient registration.

What this study is about