Clinical trial NCT00558363: ARTS - AVODART After Radical Therapy For Prostate Cancer Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms, Prostate
Prostate Cancer After a Radical Treatment
Keywords: Prostate Cancer
AVODART
PSA
dutasteride
PSADT
Prostate specific antigen
radical therapy
doubling time
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-11-14
Enrollment: 294
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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)

Eligibility criteria: 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

Primary outcomes:
measure: Time to Prostate-specific Antigen (PSA) Doubling From Baseline (in Days)
timeFrame: up to 28 months
measure: Number of Participants With PSA Doubling From Baseline
timeFrame: up to 28 months
measure: Time to PSA Doubling From Baseline (in Days) Within Year 1
timeFrame: up to 16 months
measure: Number of Participants With PSA Doubling From Baseline During Year 1
timeFrame: up to 16 months
Secondary outcomes:
measure: Time to Disease Progression From Baseline (in Days)
timeFrame: up to 28 months
measure: Number of Participants With Disease Progression
timeFrame: up to 28 months
measure: Number of Participants Classified as Treatment Responders at Months 3, 6, 9, 12, 15, 18, 21, and 24
timeFrame: Months 3, 6, 9, 12, 15, 18, 21, and 24
measure: Time to PSA Rise From Baseline (in Days)
timeFrame: up to 28 months
measure: Number of Participants With a PSA Rise From Baseline
timeFrame: up to 28 months
measure: Time to PSA Progression (in Days)
timeFrame: up to 28 months
measure: Number of Participants With PSA Progression
timeFrame: up to 28 months
measure: Change in Total PSA From Baseline at Months 12 and 24
timeFrame: Baseline; Months 12 and 24
measure: Percent Change in Total PSA From Baseline at Months 12 and 24
timeFrame: Baseline; Months 12 and 24
measure: Change in PSA From Nadir PSA at Months 12 and 24
timeFrame: Baseline; Months 12 and 24
measure: Percent Change in PSA From Nadir PSA at Months 12 and 24
timeFrame: Baseline; Months 12 and 24
measure: Number of Participants With the Indicated Change in PSA Doubling Time (PSADT) From Baseline at Month 12, Month 24, and End-of-treatment (up to 28 Months)
timeFrame: Baseline; Month 12, Month 24, End-of-Treatment (up to 28 months)
measure: Changes From Baseline in Disease-related Anxiety Measured by the Memorial Anxiety Scale for Prostate Cancer (MAX-PC)
timeFrame: Baseline; Months 3, 6, 12, 18, and 24
measure: Number of Participants With a Shift From Normal at Baseline to at Least One Abnormal Laboratory Value for Any Parameter Any Time During the Study
timeFrame: Baseline; up to 28 months
measure: Number of Participants With a Threshold Laboratory Value for Any Parameter at Baseline (BL) and Any Time Post-baseline
timeFrame: Baseline; up to 28 months
measure: Number of Participants With Palpable Breast Tissue (PBT) at Baseline (BL) and Any Time Post-baseline
timeFrame: Baseline; up to 28 months
measure: Number of Participants With Nipple Tenderness (NT) at Baseline (BL) and Any Time Post-baseline
timeFrame: Baseline; up to 28 months
measure: Number of Participants With a Digital Rectal Examination (DRE) Evaluation Changing From Normal/Diffusely Enlarged at Baseline to Focal Abnormality at Any Time Post-baseline
timeFrame: Baseline; up to 28 months
measure: Number of Participants With Threshold Vital Signs at Baseline and Any Time Post-baseline
timeFrame: Baseline; up to 28 months
Other outcomes:
Locations:
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Kouvola
country: Finland
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Angers Cedex 9
country: France
facility: GSK Investigational Site
city: Chambery
country: France
facility: GSK Investigational Site
city: Créteil
country: France
facility: GSK Investigational Site
city: Lyon Cedex 03
country: France
facility: GSK Investigational Site
city: Orleans
country: France
facility: GSK Investigational Site
city: Aichach
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Hagenow
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Oranienburg
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Schwedt
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Marburg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Seligenstadt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Wismar
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-vorpommern
city: Leer
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Dessau
country: Germany
facility: GSK Investigational Site
state: Sachsen-anhalt
city: Eisleben
country: Germany
facility: GSK Investigational Site
state: Sachsen-anhalt
city: Hettstedt
country: Germany
facility: GSK Investigational Site
state: Sachsen-anhalt
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Kiel
country: Germany
facility: GSK Investigational Site
state: Schleswig-holstein
city: Ilmenau
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Hengelo
country: Netherlands
facility: GSK Investigational Site
city: Maastricht
country: Netherlands
facility: GSK Investigational Site
city: Nijmegen
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Tilburg
country: Netherlands
facility: GSK Investigational Site
city: Winterswijk
country: Netherlands
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Alava
country: Spain
facility: GSK Investigational Site
city: Alcala de Henares (madrid)
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Bormujo (sevilla)
country: Spain
facility: GSK Investigational Site
city: Getafe
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Guadalajara
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Marbella
country: Spain
facility: GSK Investigational Site
city: Mendaro, Guipuzcoa
country: Spain
facility: GSK Investigational Site
city: Murcia
country: Spain
facility: GSK Investigational Site
city: Pamplona
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valladolid
country: Spain
facility: GSK Investigational Site
city: Göteborg
country: Sweden
facility: GSK Investigational Site
city: Göteborg
country: Sweden
facility: GSK Investigational Site
city: Malmö
country: Sweden
facility: GSK Investigational Site
city: Umeå
country: Sweden
facility: GSK Investigational Site
city: Uppsala
country: Sweden
facility: GSK Investigational Site
city: Örebro
country: Sweden
facility: GSK Investigational Site
city: Exeter
country: United Kingdom
facility: GSK Investigational Site
state: Devon
city: Stevenage
country: United Kingdom
facility: GSK Investigational Site
state: Hertfordshire
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
state: Nottinghamshire
city: Bath
country: United Kingdom
facility: GSK Investigational Site
state: Somerset
city: Bristol
country: United Kingdom
facility: GSK Investigational Site
city: High Heaton, Newcastle Upon Tyne
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Schroder F, Bangma C, Angulo JC, Alcaraz A, Colombel M, McNicholas T, Tammela TL, Nandy I, Castro R. Dutasteride treatment over 2 years delays prostate-specific antigen progression in patients with biochemical failure after radical therapy for prostate cancer: results from the randomised, placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS). Eur Urol. 2013 May;63(5):779-87. doi: 10.1016/j.eururo.2012.11.006. Epub 2012 Nov 12.