ARTS - AVODART After Radical Therapy For Prostate Cancer Study

A Randomised, Double-Blind, Placebo-Controlled Trial Assessing the Efficacy and Safety of Dutasteride (AVODART™) 0.5 mg in Extending the Time to PSA Doubling in Men With Prostate Cancer and Biochemical Failure (PSA Increase) After Radical Therapy With Curative Intent

ARI109924 will be a 2-year, multicentre, randomised, double-blind, placebo-controlled trial assessing the efficacy and safety of dutasteride in extending time to prostate specific antigen (PSA) doubling in men who have been treated for clinically localised prostate cancer (PCa) with a radical therapy (radical prostatectomy, primary radiotherapy or salvage radiotherapy) with curative intent but who experience a biochemical failure (PSA rise) afterwards without signs or symptoms of metastases.

A Randomised, Double-Blind, Placebo-Controlled Trial Assessing the Efficacy and Safety of Dutasteride (AVODART™) 0.5 mg in Extending the Time to PSA Doubling in Men with Prostate Cancer and Biochemical Failure (PSA increase) after Radical Therapy with Curative Intent (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