Inclusion Criteria:

- 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.

Exclusion Criteria:

- Patients with a history of other invasive malignancy, except:adequately treated non
melanoma skin cancer or other solid tumors curatively treated with no evidence of
disease for 3 years.

- Patients with known brain metastases or leptomemingeal disease are excluded from this
clinical trial because of their poor prognosis and because they often develop
progressive neurological dysfunction that would confound the evaluation of nerologic
and other adverse events.

- History of allergic reactions and/or sensitivity attributed to compounds of similar
chemical or biological composition to Vandetanib or other agents used in the study.

- Other serious intercurrent illness or medical condition that might be aggravated by
protocol treatment including;myocardial infarction within 6 months prior to study
entry, congestive heart failure, unstable angina,cardiomyopathy, unstable ventricular
arrhythmias,OTc (Bazett's) >480msec Uncontrolled hypertension (systolic >160,
diatolic >100) Uncontrolled psychotic disorders, serious infections,peptic ulcer
disease,history of bleeding diathesis

- Upper gasrtointerstinal or other conditions that would preclude compliance with oral
medication

- Patients with immune deficiency are at increased risk of lethal infections when
treated with Marrow-suppressive therapy. Therefore, HIV positive patients receiving
combination ant-retroviral therapy are excluded from study because of possible risk
of lethal infection and additionally because of the possible pharmacokinetic
interactions with Vandetanib. Appropriate studies will be undertaken in patients
receiving combination anti-retroviral therapy when indicated.

- Patients who require escalating amounts of narcotic therapy to control pain e.g.
morphine equivalent dose >30mg/day) since these patients would more appropriately be
offered systemic chemotherapy

- Patients who require therapeutic anticoagulation with warfarin.

- Patients who require the following medication:concomittant use of warfarin, Class 1A
antiarrythmics (e.g., quinidine, procainamide, disopyramide) Class

1C antiarrhythmics (e.g.,flecainide, propafenone), Class III antiarrhythmics (e.g.,
amiodarone, sotalol, ibutilide), antipsychotics (e.g., thioridazine, chlorpromazine,
pimozide, haloperidol, droperidol), tri/tetracyclic antidepressants (e.g.,
amitriptyline, imipramine, maprotiline), ketoconazole, antiepileptics and macrolide
antibiotics.

- Patients who cannot stop ingestion of grapefruit/juice.