Inclusion Criteria:

• Patients must have histological or cytological diagnosis of adenocarcinoma of the prostate.
• Patients must have metastatic or locally recurrent disease.
• Patients must have documented evidence of PSA progression
• The PSA must be > 5 ng/mL at the time of study entry.
• ECOG performance status of 0, 1 or 2.
• Patients must have a life expectancy of at least 12 weeks in the judgment of the investigator.
• Chemotherapy: patients must have received prior docetaxel based chemotherapy (either as a single agent or in combination). Patients must have evidence of progression while receiving docetaxel based chemotherapy or within 6 months after the completion of docetaxel based chemotherapy. Prior adjuvant or neoadjuvant chemotherapy is permitted provided therapy was completed > 12 months prior to registration. Prior therapy with mitoxantrone or experimental non-cytotoxic chemotherapy is permitted (e.g. monoclonal antibodies, vaccine therapy, receptor tyrosine kinase inhibitors).
• Hormonal Therapy: Prior hormone therapy is permitted. Patients must be hormone refractory and have been previously and currently treated with androgen ablative therapy (medical or surgical castration). Therapy with LHRH agonist must continue for those prostate cancer patients already receiving this treatment at the time of enrollment. If the patient has discontinued the LHRH agonist, this must be restarted and the castrate level of testosterone must be present. Patients must have discontinued any use of non-steroidal antiandrogens (e.g. bicalutamide, nilutamide, flutamide) at least 6 weeks prior to initiation of protocol therapy.
• Radiation: Prior external beam radiation is permitted provided a minimum of 4 weeks has elapsed between the last dose and enrollment to the trial. Exceptions may be made for low dose, nonmyelosuppressive radiotherapy after consultation with the principal investigator. Prior strontium is not permitted. Patients must have had less than 30% of marrow bearing areas irradiated.
• Steroids: Current treatment with steroids are permitted provided the dose is less than or equivalent to a daily dose of prednisone of 20mg.
• Laboratory Requirements - within 7 days prior to enrollment Hematology: absolute granulocytes ≥ 1.5 x 109/Lplatelets ≥ 100 x 109/Lhemoglobin ≥ 90 g/L Biochemistry: bilirubin ≤ 1.0 x upper limit of normal serum creatinine ≤ 1.5 x upper limit of normal AST/ALT ≤ 2.5 x upper limit of normal
• Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements.
• Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre.

Exclusion Criteria:

• Patients with a history of other invasive cancer, except adequately treated non-melanoma skin cancer or other solid tumours curatively treated with no evidence of disease for > 3 years.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Patupilone or other agents used in the study.
• Other serious intercurrent illness of medical condition that might be aggravated by protocol treatment including: myocardial infarction within 6 months prior to study entry congestive heart failure unstable angina active cardiomyopathy unstable ventricular arrhythmia uncontrolled hypertension uncontrolled psychotic disorders serious infections active peptic ulcer disease
• HIV-positive patients receiving combination anti-retroviral therapy
• Peripheral neuropathy > grade 1.
• Patients who have received treatment with other investigational agents or anti-cancer therapy < 21 days prior to date of protocol treatment.
• Patients receiving anticoagulation with warfarin (Coumadin®).
• Patients with grade ≥ 1 diarrhea.