ARTS - AVODART After Radical Therapy For Prostate Cancer Study

Condition(s) targeted: Prostate Cancer After a Radical Treatment

Intervention: Avodart/placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, MD, Study Director, Affiliation: GlaxoSmithKline

Overall contact:
US GSK Clinical Trials Call Center, Phone: 877-379-3718

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.

Official title: See Detailed Description

Study design: Treatment, Randomized, Double-Blind, Single Group Assignment, Safety/Efficacy Study

Primary outcome: To assess the effect of dutasteride 0.5 mg daily compared to placebo on time to PSA doubling after a two year treatment.

Secondary outcome:

To assess the effect of dutasteride compared to placebo after a two year treatment on - disease progression - treatment response - changes in PSA and PSADT - evaluate changes in patient anxiety - evaluate the safety

Time to disease progression and the percentage of patients with disease progression in the dutasteride group compared to the placebo group, as defined by any of the following:

PSA doubling time of ≤3 months and confirmed in an immediate subsequent PSA determination (i.e. within 2 weeks)

PSA >20ng/mL (primary radiotherapy patients) or PSA >10ng/mL (radical prostatectomy with or without salvage radiotherapy patients) associated with at least a 50% increase from the baseline PSA measurement

and confirmed in an immediate subsequent PSA determination (i.e. within 2 weeks)

Any confirmed progression in the clinical stage (T stage)

Need for any additional prostate cancer rescue therapy (e.g., gonadotropinreleasing hormone [GnRH] agonists, antiandrogens etc.)

Metastatic disease confirmed by a positive bone scan

Percentage of patients with treatment response in the dutasteride group compared to the placebo group, defined as:

The percent of patients with any PSA decrease or an increase ≤15% from baseline to up to 24 months of treatment confirmed in all PSA measurements

Changes in PSA including:

Time to PSA rise from baseline and percentage of patients with a PSA rise from baseline,

defined as first PSA value showing a >15% increase from baseline confirmed in all subsequent measurements (baseline PSA is defined as the last PSA measurement prior to randomisation)

Time to PSA progression and percentage of patients with PSA progression based on the definition of a patient experiencing PSA doubling time ≤3 months or PSA >20ng/mL

(primary radiotherapy patients) or PSA >10ng/mL (radical prostatectomy with or without salvage radiotherapy patients)

associated with at least a 50% increase from the baseline PSA measurement and confirmed in an immediate subsequent PSA determination (i.e. within 2 weeks)

Detailed description: 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)

Minimum age: 18 Years. Maximum age: 85 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 4. 2. Inclusion Criteria

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

Demographic and baseline characteristics:

1. Males <85 years of age

2. No clinically relevant abnormal findings on the screening ECG

3. Patients with asymptomatic PSA failure following radical therapy with curative intent for clinically localised prostate cancer. PSA failure is defined as:

a. After primary radiotherapy: i. 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 ii. Time from radiotherapy should be at least 1 year from termination of radiotherapy treatment b. After radical prostatectomy with or without salvage radiotherapy: i. 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)

4. Serum PSA levels:

1. ≥2 ng/mL and ≤20ng/mL for primary radiotherapy patients

2. ≥0. 4 ng/ml and ≤10ng/ml for radical prostatectomy with or without salvage radiotherapy patients

5. PSADT >3 months and ≤24 months

6. Clinical stage T1-T3a N0 M0

7. Non-metastatic prostate cancer, as confirmed on a negative bone scan performed within 6 months prior to randomisation (Visit 2)3.

8. No evidence of local recurrence in radical prostatectomy or salvage radiotherapy patients

9. Expected survival ≥2 years

10. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (see Appendix 1)

Miscellaneous:

11. Able to swallow and retain oral medication

12. Able and willing to participate in the full 2 years of the study

13. Able to read and write (the MAX-PC questionnaire is self-administered), understand instructions related to study procedures and give written informed consent

14. 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:

- Demographic and baseline characteristics:

1. 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

2. 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).

3. Serum creatinine >1. 5 x ULN

4. History of another malignancy within 5 years that could affect the diagnosis of prostate cancer

5. History or current evidence of drug or alcohol abuse within 12 months prior to Visit 1

6. 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

7. Known hypersensitivity to any 5-AR inhibitor or to any drug chemically related to dutasteride

Disease characteristics:

1. Serum PSA levels

1. >20 ng/mL in primary radiotherapy patients

2. >10 ng/mL in radical prostatectomy with or without salvage radiotherapy patients

2. PSADT ≤3 months or >24 months

3. Biochemical failures in post brachytherapy patients

4. Clinical stage N+ or M+

5. Patient has previously been treated for prostate cancer with any of the following:

1. Chemotherapy

2. Oestrogens (e. g. megestrol, medroxyprogesterone, cyproterone, Diethylstilbestrol [DES])

3. 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]

4. 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)

5. Orchiectomy

Concomitant medications:

1. Glucocorticoids, except inhaled or topical, are not permitted within 3 months prior to Visit 1 or during the study

2. Current and/or previous use of finasteride (Proscar, Propecia) or dutasteride (GI198745, AVODART™) exposure within 6 months prior to Visit 1

3. Anabolic steroids within 6 months prior to Visit 1

4. Participation in any other investigational or marketed drug trial within the 30 days prior to Visit 1 or any time during the study period

US GSK Clinical Trials Call Center, Phone: 877-379-3718

GSK Investigational Site, Tallinn 1162, Estonia; Active, not recruiting

GSK Investigational Site, Tallinn 13419, Estonia; Active, not recruiting

GSK Investigational Site, Tallinn 10617, Estonia; Completed

GSK Investigational Site, Tampere 33521, Finland; Active, not recruiting

GSK Investigational Site, Kouvola 45200, Finland; Active, not recruiting

GSK Investigational Site, Turku 20520, Finland; Withdrawn

GSK Investigational Site, Oulu 90100, Finland; Recruiting

GSK Investigational Site, Mantes La Jolie 78200, France; Active, not recruiting

GSK Investigational Site, Lyon Cedex 03 69437, France; Recruiting

GSK Investigational Site, Paris Cedex 10 75475, France; Active, not recruiting

GSK Investigational Site, Pontoise Cedex 95303, France; Active, not recruiting

GSK Investigational Site, Chambery 73011, France; Recruiting

GSK Investigational Site, Caen cedex 14050, France; Withdrawn

GSK Investigational Site, Orleans 45100, France; Recruiting

GSK Investigational Site, Créteil Cedex 94010, France; Recruiting

GSK Investigational Site, Angers 49933, France; Recruiting

GSK Investigational Site, Berlin 13187, Germany; Recruiting

GSK Investigational Site, Berlin 10249, Germany; Recruiting

GSK Investigational Site, Berlin 12627, Germany; Recruiting

GSK Investigational Site, TILBURG 5022 GC, Netherlands; Recruiting

GSK Investigational Site, NIJMEGEN 6525 GA, Netherlands; Recruiting

GSK Investigational Site, HENGELO 7555 DL, Netherlands; Recruiting

GSK Investigational Site, EINDHOVEN 5623 EJ, Netherlands; Withdrawn

GSK Investigational Site, NIJMEGEN 6532 SZ, Netherlands; Withdrawn

GSK Investigational Site, AMSTERDAM 1081 HV, Netherlands; Withdrawn

GSK Investigational Site, Maastricht 6229 HX, Netherlands; Recruiting

GSK Investigational Site, AMSTERDAM 1091 AC, Netherlands; Recruiting

GSK Investigational Site, WINTERSWIJK 7101 BN, Netherlands; Recruiting

GSK Investigational Site, ROTTERDAM 3015 CE, Netherlands; Active, not recruiting

GSK Investigational Site, Moscow 128128, Russian Federation; Recruiting

GSK Investigational Site, Moscow 117 837, Russian Federation; Recruiting

GSK Investigational Site, Moscow, Russian Federation; Withdrawn

GSK Investigational Site, Moscow 117 049, Russian Federation; Not yet recruiting

GSK Investigational Site, Moscow 115478, Russian Federation; Recruiting

GSK Investigational Site, Moscow 119 881, Russian Federation; Recruiting

GSK Investigational Site, Valencia 46010, Spain; Recruiting

GSK Investigational Site, Alava 01004, Spain; Recruiting

GSK Investigational Site, Pamplona 31008, Spain; Recruiting

GSK Investigational Site, Granada 18014, Spain; Recruiting

GSK Investigational Site, Barcelona 08025, Spain; Completed

GSK Investigational Site, Sevilla 41013, Spain; Withdrawn

GSK Investigational Site, Valladolid 47010, Spain; Recruiting

GSK Investigational Site, Guadalajara 19002, Spain; Recruiting

GSK Investigational Site, Barcelona 8907, Spain; Recruiting

GSK Investigational Site, Bormujo (Sevilla) 41930, Spain; Recruiting

GSK Investigational Site, Mendaro, Guipuzcoa 20850, Spain; Recruiting

GSK Investigational Site, Getafe 28905, Spain; Recruiting

GSK Investigational Site, Barcelona 08036, Spain; Active, not recruiting

GSK Investigational Site, Sevilla 41013, Spain; Active, not recruiting

GSK Investigational Site, Madrid 28046, Spain; Active, not recruiting

GSK Investigational Site, Murcia 30008, Spain; Active, not recruiting

GSK Investigational Site, Alcala De Henares (Madrid), Spain; Active, not recruiting

GSK Investigational Site, Marbella 29600, Spain; Recruiting

GSK Investigational Site, Alcázar de San Juan (Ciudad Real) 13600, Spain; Withdrawn

GSK Investigational Site, Göteborg SE-417 17, Sweden; Recruiting

GSK Investigational Site, BORÅS SE-503 32, Sweden; Active, not recruiting

GSK Investigational Site, GÄVLE SE-801 87, Sweden; Withdrawn

GSK Investigational Site, UMEÅ SE-901 85, Sweden; Recruiting

GSK Investigational Site, MALMÖ SE-205 02, Sweden; Recruiting

GSK Investigational Site, Örebro SE-701 85, Sweden; Recruiting

GSK Investigational Site, GÖTEBORG SE-412 55, Sweden; Recruiting

GSK Investigational Site, Uppsala SE-751 85, Sweden; Recruiting

GSK Investigational Site, High Heaton, Newcastle Upon Tyne NE7 7DN, United Kingdom; Recruiting

GSK Investigational Site, Bristol BS2 8HW, United Kingdom; Recruiting

GSK Investigational Site, Muenchen, Bayern 81927, Germany; Withdrawn

GSK Investigational Site, Aichach, Bayern 86551, Germany; Recruiting

GSK Investigational Site, Hennigsdorf, Brandenburg 16761, Germany; Active, not recruiting

GSK Investigational Site, Oranienburg, Brandenburg 16515, Germany; Recruiting

GSK Investigational Site, Hagenow, Brandenburg 19230, Germany; Recruiting

GSK Investigational Site, Schwedt, Brandenburg 16303, Germany; Recruiting

GSK Investigational Site, Exeter, Devon EX2 5DW, United Kingdom; Recruiting

GSK Investigational Site, Stevenage, Hertfordshire SG2 4AB, United Kingdom; Recruiting

GSK Investigational Site, Marburg, Hessen 35039, Germany; Recruiting

GSK Investigational Site, Frankfurt, Hessen 60326, Germany; Active, not recruiting

GSK Investigational Site, Seligenstadt, Hessen 63500, Germany; Recruiting

GSK Investigational Site, Wismar, Mecklenburg-Vorpommern 23970, Germany; Recruiting

GSK Investigational Site, Leer, Niedersachsen 26789, Germany; Recruiting

GSK Investigational Site, Nottingham, Nottinghamshire NG5 1PB, United Kingdom; Recruiting

GSK Investigational Site, Leipzig, Sachsen 04109, Germany; Recruiting

GSK Investigational Site, Hettstedt, Sachsen-Anhalt 06333, Germany; Recruiting

GSK Investigational Site, Dessau, Sachsen-Anhalt 06844, Germany; Recruiting

GSK Investigational Site, Eisleben, Sachsen-Anhalt 06295, Germany; Recruiting

GSK Investigational Site, Kiel, Schleswig-Holstein 24143, Germany; Recruiting

GSK Investigational Site, Bath, Somerset BA1 1BX, United Kingdom; Recruiting

GSK Investigational Site, Hartshill, Stoke-on-Trent, Staffordshire ST4 7LN, United Kingdom; Active, not recruiting

GSK Investigational Site, Ilmenau, Thueringen 98693, Germany; Recruiting

Starting date: November 2007
Ending date: March 2011
Last updated: November 13, 2008