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

Sponsors

Lead Sponsor: GlaxoSmithKline

Source GlaxoSmithKline
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)

Overall Status Completed
Start Date November 2007
Completion Date March 2011
Primary Completion Date December 2010
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Time to Prostate-specific Antigen (PSA) Doubling From Baseline (in Days) up to 28 months
Number of Participants With PSA Doubling From Baseline up to 28 months
Time to PSA Doubling From Baseline (in Days) Within Year 1 up to 16 months
Number of Participants With PSA Doubling From Baseline During Year 1 up to 16 months
Secondary Outcome
Measure Time Frame
Time to Disease Progression From Baseline (in Days) up to 28 months
Number of Participants With Disease Progression up to 28 months
Number of Participants Classified as Treatment Responders at Months 3, 6, 9, 12, 15, 18, 21, and 24 Months 3, 6, 9, 12, 15, 18, 21, and 24
Time to PSA Rise From Baseline (in Days) up to 28 months
Number of Participants With a PSA Rise From Baseline up to 28 months
Time to PSA Progression (in Days) up to 28 months
Number of Participants With PSA Progression up to 28 months
Change in Total PSA From Baseline at Months 12 and 24 Baseline; Months 12 and 24
Percent Change in Total PSA From Baseline at Months 12 and 24 Baseline; Months 12 and 24
Change in PSA From Nadir PSA at Months 12 and 24 Baseline; Months 12 and 24
Percent Change in PSA From Nadir PSA at Months 12 and 24 Baseline; Months 12 and 24
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) Baseline; Month 12, Month 24, End-of-Treatment (up to 28 months)
Changes From Baseline in Disease-related Anxiety Measured by the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) Baseline; Months 3, 6, 12, 18, and 24
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 Baseline; up to 28 months
Number of Participants With a Threshold Laboratory Value for Any Parameter at Baseline (BL) and Any Time Post-baseline Baseline; up to 28 months
Number of Participants With Palpable Breast Tissue (PBT) at Baseline (BL) and Any Time Post-baseline Baseline; up to 28 months
Number of Participants With Nipple Tenderness (NT) at Baseline (BL) and Any Time Post-baseline Baseline; up to 28 months
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 Baseline; up to 28 months
Number of Participants With Threshold Vital Signs at Baseline and Any Time Post-baseline Baseline; up to 28 months
Enrollment 294
Condition
Intervention

Intervention Type: Drug

Intervention Name: Avodart

Description: 0.5 mg administered orally once daily

Arm Group Label: Avodart

Other Name: Avodart/placebo

Intervention Type: Other

Intervention Name: placebo

Description: Patients will be randomized at Visit 2 in 1:1 ratio to receive either 0.5 mg dutasteride or placebo

Arm Group Label: Placebo Arm

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

Gender: All

Minimum Age: 18 Years

Maximum Age: 85 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
GSK Clinical Trials Study Director GlaxoSmithKline
Location
Facility:
GSK Investigational Site | Tallinn, 1162, Estonia
GSK Investigational Site | Tallinn, 13419, Estonia
GSK Investigational Site | Kouvola, 45200, Finland
GSK Investigational Site | Oulu, 90100, Finland
GSK Investigational Site | Tampere, 33521, Finland
GSK Investigational Site | Angers Cedex 9, 49933, France
GSK Investigational Site | Chambery, 73011, France
GSK Investigational Site | Créteil, 94000, France
GSK Investigational Site | Lyon Cedex 03, 69437, France
GSK Investigational Site | Orleans, 45100, France
GSK Investigational Site | Aichach, Bayern, 86551, Germany
GSK Investigational Site | Hagenow, Brandenburg, 19230, Germany
GSK Investigational Site | Oranienburg, Brandenburg, 16515, Germany
GSK Investigational Site | Schwedt, Brandenburg, 16303, Germany
GSK Investigational Site | Marburg, Hessen, 35039, Germany
GSK Investigational Site | Seligenstadt, Hessen, 63500, Germany
GSK Investigational Site | Wismar, Mecklenburg-vorpommern, 23970, Germany
GSK Investigational Site | Leer, Niedersachsen, 26789, Germany
GSK Investigational Site | Dessau, Sachsen-anhalt, 06844, Germany
GSK Investigational Site | Eisleben, Sachsen-anhalt, 06295, Germany
GSK Investigational Site | Hettstedt, Sachsen-anhalt, 06333, Germany
GSK Investigational Site | Leipzig, Sachsen, 04109, Germany
GSK Investigational Site | Kiel, Schleswig-holstein, 24143, Germany
GSK Investigational Site | Ilmenau, Thueringen, 98693, Germany
GSK Investigational Site | Berlin, 10249, Germany
GSK Investigational Site | Berlin, 12627, Germany
GSK Investigational Site | Berlin, 13187, Germany
GSK Investigational Site | Amsterdam, 1091 AC, Netherlands
GSK Investigational Site | Hengelo, 7555 DL, Netherlands
GSK Investigational Site | Maastricht, 6229 HX, Netherlands
GSK Investigational Site | Nijmegen, 6525 GA, Netherlands
GSK Investigational Site | Rotterdam, 3015 CE, Netherlands
GSK Investigational Site | Tilburg, 5022 GC, Netherlands
GSK Investigational Site | Winterswijk, 7101 BN, Netherlands
GSK Investigational Site | Moscow, 115478, Russian Federation
GSK Investigational Site | Moscow, 117 837, Russian Federation
GSK Investigational Site | Moscow, 119 881, Russian Federation
GSK Investigational Site | Moscow, 128128, Russian Federation
GSK Investigational Site | Alava, 01004, Spain
GSK Investigational Site | Alcala de Henares (madrid), Spain
GSK Investigational Site | Barcelona, 08036, Spain
GSK Investigational Site | Barcelona, 8907, Spain
GSK Investigational Site | Bormujo (sevilla), 41930, Spain
GSK Investigational Site | Getafe, 28905, Spain
GSK Investigational Site | Granada, 18014, Spain
GSK Investigational Site | Guadalajara, 19002, Spain
GSK Investigational Site | Madrid, 28046, Spain
GSK Investigational Site | Marbella, 29600, Spain
GSK Investigational Site | Mendaro, Guipuzcoa, 20850, Spain
GSK Investigational Site | Murcia, 30008, Spain
GSK Investigational Site | Pamplona, 31008, Spain
GSK Investigational Site | Sevilla, 41013, Spain
GSK Investigational Site | Valencia, 46010, Spain
GSK Investigational Site | Valladolid, 47012, Spain
GSK Investigational Site | Göteborg, SE-412 55, Sweden
GSK Investigational Site | Göteborg, SE-413 46, Sweden
GSK Investigational Site | Malmö, SE-205 02, Sweden
GSK Investigational Site | Umeå, SE-901 85, Sweden
GSK Investigational Site | Uppsala, SE-751 85, Sweden
GSK Investigational Site | Örebro, SE-701 85, Sweden
GSK Investigational Site | Exeter, Devon, EX2 5DW, United Kingdom
GSK Investigational Site | Stevenage, Hertfordshire, SG2 4AB, United Kingdom
GSK Investigational Site | Nottingham, Nottinghamshire, NG5 1PB, United Kingdom
GSK Investigational Site | Bath, Somerset, BA1 1BX, United Kingdom
GSK Investigational Site | Bristol, BS2 8HW, United Kingdom
GSK Investigational Site | High Heaton, Newcastle Upon Tyne, NE7 7PN, United Kingdom
Location Countries

Estonia

Finland

France

Germany

Netherlands

Russian Federation

Spain

Sweden

United Kingdom

Verification Date

December 2011

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Avodart

Type: Experimental

Description: Patients will receive a 3-month supply of study drug or placebo. Patients will be instructed to take one capsule by mouth once daily. Study medication will be supplied at 3-month intervals during scheduled clinic visits for a total of 24 months.

Label: Placebo Arm

Type: Placebo Comparator

Description: Patients will receive a 3-month supply of study drug or placebo. Patients will be instructed to take one capsule by mouth once daily. Study medication will be supplied at 3-month intervals during scheduled clinic visits for a total of 24 months.

Acronym ARTS
Study Design Info

Allocation: Randomized

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov