Inclusion Criteria:

- Age >18 years.

- Signed informed consent.

- Able to comply with protocol requirements.

- Histologically, cytologically or biochemically documented adenocarcinoma of the
prostate, clinically refractory or resistant to hormone therapy, as documented by
progression following at least one hormonal therapy, which must include orchidectomy
or gonadotropin releasing hormone agonist (GnRHa).

- Progressive Disease (PD) is defined as a minimum of three consecutive serum PSA
measurements obtained at least 7 days apart within the previous 3 months of start of
trial, which document progressively increasing values. Patients with progression of
measurable disease (RECIST) or progression of bone disease must also fit the
criterion for PSA progression.

- Patients must have documented progression (as defined above) following anti-androgen
withdrawal of 4 weeks duration for flutamide and 6 weeks for bicalutamide or
nilutamide. For a patient who has withdrawn from anti-androgen therapy less than 6
months prior to inclusion in trial one of the following criteria is also required:

- Following the completion of the anti-androgen withdrawal period one PSA higher than
the last pre-withdrawal PSA.

- Or Following the completion of the anti-androgen withdrawal period if the PSA value
has decreased, he can still qualify if 2 increases in PSA are documented after the
post- withdrawal nadir.

- PSA > 5ng/mL.

- Life expectancy of at least 12 weeks.

- ECOG performance status 0-1 (see appendix 11.2).

- Stable analgesia requirements.

- Adequate hepatic function: total bilirubin < 26µmol/L, ALT and/or AST < 1.5x upper
limit of normal (ULN).

- Adequate renal function: serum creatinine < 1.5 x ULN.

- INR Prothrombin time (PT) and partial thromboplastin time (PTT) <1.5 upper limit of
normal.

- Absolute neutrophil count (ANC) > 1.5 x 109l, Platelets > 100 x 109/l.

- Haemoglobin > 9.0 g/dl.

- LVEF > 50 % on MUGA scan or echocardiogram.

- Castrate testosterone level [< 20ng/dl or <0.69nM (nM/L x 28.8 = ng/dl)], which must
be maintained during the duration of the trial by orchidectomy or medical castration.

- Patient on oral or intravenous bisphosphonates are allowed to enter the trial as long
as they have been on bisphosphonates for a minimum of 3 months.

Exclusion Criteria:

- Prior treatment with inhibitors of EGFR, HER 2 and/or VEGF receptors.

- Prior treatment with cytotoxic chemotherapy.

- Known hypersensitivity to the trial drugs or their excipients.

- Systemic corticosteroids 28 days before screening (inhaled corticosteroids prescribed
for bronchospasm are allowed). Patients on long-term stable-dose steroids for
concurrent illness are not excluded.

- Treatment with any investigational drug within 28 days of trial onset.

- History of other malignancies which could affect compliance with the protocol or
interpretation of results within 5-years. Patients with adequately treated basal or
squamous cell skin cancer are generally eligible.

- Serious illness or concomitant non-oncological disease such as neurologic,
psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or
laboratory abnormality that may increase the risk associated with trial participation
or trial drug administration and in the judgment of the investigator would make the
patient inappropriate for entry into the trial.

- Major injuries and/or surgery within 4 weeks of trial onset or bone fracture and
planned surgical procedures during the trial period.

- Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina,
history of infarction within past 9 months, congestive heart failure > NYHA II) (see
appendix 11.5).

- History of haemorrhagic or thrombotic event in the past 12 months. Known inherited
predisposition to bleeds or to thrombosis.

- Patient with history or clinical evidence of CNS disease or brain metastases.

- Patients with symptoms of impending or established spinal cord compression.

- Gastrointestinal disorders or abnormalities that would inhibit absorption of the
trial drug.

- Patients who require full-dose anticoagulation.

- Radio- or immunotherapy within the past four weeks prior to treatment with the trial
drug.

- Patients unable to comply with the protocol.

- Active alcohol or drug abuse.