ARTS - AVODART After Radical Therapy For Prostate Cancer Study

Inclusion Criteria:

Patients eligible for enrolment in the study must meet all of the following criteria:

* Males \<85 years of age
* No clinically relevant abnormal findings on the screening ECG
* Patients with asymptomatic PSA failure following radical therapy with curative intent for clinically localised prostate cancer. PSA failure is defined as:
* After primary radiotherapy:
* 3 rises in PSA levels from nadir PSA, with each determination at least 4 weeks apart and a final PSA level ≥2 ng/mL above nadir PSA
* Time from radiotherapy should be at least 1 year from termination of radiotherapy treatment
* After radical prostatectomy with or without salvage radiotherapy:
* 3 rises in PSA level from nadir PSA, with each determination at least 4 weeks apart and each PSA level ≥0.2 ng/mL and a final PSA level ≥0.4 ng/mL (nadir PSA is defined as the lowest PSA value achieved after therapy)
* Serum PSA levels:
* ≥2 ng/mL and ≤20ng/mL for primary radiotherapy patients
* ≥0.4 ng/ml and ≤10ng/ml for radical prostatectomy with or without salvage radiotherapy patients
* PSADT \>3 months and ≤24 months
* Clinical stage T1-T3a N0 M0
* Non-metastatic prostate cancer, as confirmed on a negative bone scan performed within 6 months prior to randomisation (Visit 2)3.
* No evidence of local recurrence in radical prostatectomy or salvage radiotherapy patients
* Expected survival ≥2 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (see Appendix 1)

Miscellaneous:

* Able to swallow and retain oral medication
* Able and willing to participate in the full 2 years of the study
* Able to read and write (the MAX-PC questionnaire is self-administered), understand instructions related to study procedures and give written informed consent
* In France, a patient will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

* Any unstable serious co-existing medical condition(s) including but not limited to myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure or cerebrovascular accident within 6 months prior to Visit 1, or uncontrolled diabetes or peptic ulcer disease which is uncontrolled by medical management
* Abnormal liver function tests (greater than 2 times the upper limit of normal \[ULN\] for alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] or alkaline phosphatase \[ALP\] or \>1.5 x ULN for bilirubin).
* Serum creatinine \>1.5 x ULN
* History of another malignancy within 5 years that could affect the diagnosis of prostate cancer
* History or current evidence of drug or alcohol abuse within 12 months prior to Visit 1
* History of any illness (including psychiatric) that, in the opinion of the investigator, might confound the results of the study or pose additional risk to the patient
* Known hypersensitivity to any 5-AR inhibitor or to any drug chemically related to dutasteride

Disease characteristics:

* Serum PSA levels
* \>20 ng/mL in primary radiotherapy patients
* \>10 ng/mL in radical prostatectomy with or without salvage radiotherapy patients
* PSADT ≤3 months or \>24 months
* Biochemical failures in post brachytherapy patients
* Clinical stage N+ or M+
* Patient has previously been treated for prostate cancer with any of the following:
* Chemotherapy
* Oestrogens (e.g. megestrol, medroxyprogesterone, cyproterone, Diethylstilbestrol \[DES\])
* Drugs with anti-androgenic properties (e.g. spironolactone if \>50mg/day, flutamide, bicalutamide, ketoconazole, progestational agents), (except when used for adjuvancy or neoadjuvancy in the context of a primary radical treatment in which case their use should have been for no more than 6 months and should have completed at least 1 year before Visit 1 \[Note: the use of topical ketoconazole is permitted prior to and during the study and the use of cimetidine is permitted prior to study entry\]
* GnRH analogues (e.g., leuprolide, goserelin) except when used for adjuvancy or neoadjuvancy in the context of a primary radical treatment (in this case use should have been for no more than 6 months and should have finalised at least 1 year before Visit 1)
* Orchiectomy

Concomitant medications:

* Glucocorticoids, except inhaled or topical, are not permitted within 3 months prior to Visit 1 or during the study
* Current and/or previous use of finasteride (Proscar, Propecia) or dutasteride (GI198745, AVODART™) exposure within 6 months prior to Visit 1
* Anabolic steroids within 6 months prior to Visit 1
* Participation in any other investigational or marketed drug trial within the 30 days prior to Visit 1 or any time during the study period