ARTS - AVODART After Radical Therapy For Prostate Cancer Study

Neoplasms, Prostate Clinical Trial

— ARTS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00558363
• Other study ID #: ARI109924
• Status: Completed
• Phase: Phase 2
• First received: November 13, 2007
• Last updated: March 15, 2012
• Start date: November 2007
• Est. completion date: March 2011

Study information

• Verified date: December 2011
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 294
• Est. completion date: March 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms, Prostate
• Prostate Cancer After a Radical Treatment
• Prostatic Neoplasms

Intervention

Drug:
• Avodart
0.5 mg administered orally once daily

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

Locations

Country	Name	City	State
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tallinn
Finland	GSK Investigational Site	Kouvola
Finland	GSK Investigational Site	Oulu
Finland	GSK Investigational Site	Tampere
France	GSK Investigational Site	Angers Cedex 9
France	GSK Investigational Site	Chambery
France	GSK Investigational Site	Créteil
France	GSK Investigational Site	Lyon Cedex 03
France	GSK Investigational Site	Orleans
Germany	GSK Investigational Site	Aichach	Bayern
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Dessau	Sachsen-anhalt
Germany	GSK Investigational Site	Eisleben	Sachsen-anhalt
Germany	GSK Investigational Site	Hagenow	Brandenburg
Germany	GSK Investigational Site	Hettstedt	Sachsen-anhalt
Germany	GSK Investigational Site	Ilmenau	Thueringen
Germany	GSK Investigational Site	Kiel	Schleswig-holstein
Germany	GSK Investigational Site	Leer	Niedersachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Marburg	Hessen
Germany	GSK Investigational Site	Oranienburg	Brandenburg
Germany	GSK Investigational Site	Schwedt	Brandenburg
Germany	GSK Investigational Site	Seligenstadt	Hessen
Germany	GSK Investigational Site	Wismar	Mecklenburg-vorpommern
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Hengelo
Netherlands	GSK Investigational Site	Maastricht
Netherlands	GSK Investigational Site	Nijmegen
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Tilburg
Netherlands	GSK Investigational Site	Winterswijk
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Spain	GSK Investigational Site	Alava
Spain	GSK Investigational Site	Alcala de Henares (madrid)
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Bormujo (sevilla)
Spain	GSK Investigational Site	Getafe
Spain	GSK Investigational Site	Granada
Spain	GSK Investigational Site	Guadalajara
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Marbella
Spain	GSK Investigational Site	Mendaro, Guipuzcoa
Spain	GSK Investigational Site	Murcia
Spain	GSK Investigational Site	Pamplona
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valladolid
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Malmö
Sweden	GSK Investigational Site	Örebro
Sweden	GSK Investigational Site	Umeå
Sweden	GSK Investigational Site	Uppsala
United Kingdom	GSK Investigational Site	Bath	Somerset
United Kingdom	GSK Investigational Site	Bristol
United Kingdom	GSK Investigational Site	Exeter	Devon
United Kingdom	GSK Investigational Site	High Heaton, Newcastle Upon Tyne
United Kingdom	GSK Investigational Site	Nottingham	Nottinghamshire
United Kingdom	GSK Investigational Site	Stevenage	Hertfordshire

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Estonia,  Finland,  France,  Germany,  Netherlands,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Prostate-specific Antigen (PSA) Doubling From Baseline (in Days)	Time to PSA doubling is defined as the number of days between the baseline date and the study day of the first post-baseline PSA evaluation date (within treatment period, typically up to 24-month evaluations) on which the PSA value was at least twice as much as the baseline PSA value, and the immediate subsequent value, if available, was at least 85% of two times the baseline value. Participants who never achieved PSA doubling were censored at the last post-baseline, non-missing PSA evaluation.	up to 28 months	No
Primary	Number of Participants With PSA Doubling From Baseline	PSA doubling is defined as the first post-baseline PSA value (within treatment period, typically up to 24-month evaluations) that was at least twice as much as the baseline PSA value and was confirmed as such (at least 85% of two times the baseline PSA value) in the immediate subsequent PSA value if one is available.	up to 28 months	No
Primary	Time to PSA Doubling From Baseline (in Days) Within Year 1	Time to PSA doubling is defined as the number of days between the baseline date and the study day of the first post-baseline PSA evaluation date within Year 1 (Y1; within treatment period, typically up to 12-month evaluations) on which the PSA value was at least twice as much as the baseline PSA value, and the immediate subsequent value, if available, was at least 85% of two times the baseline value.	up to 16 months	No
Primary	Number of Participants With PSA Doubling From Baseline During Year 1	PSA doubling is defined as the first post-baseline PSA value (within treatment period, typically up to 12-month evaluations) that was at least twice as much as the baseline PSA value and was confirmed as such (at least 85% of two times the baseline PSA value) in the immediate subsequent PSA value if one is available.	up to 16 months	No
Secondary	Time to Disease Progression From Baseline (in Days)	Time to disease progression is defined as the number of days between baseline and the first occurrence of any of the following: PSA doubling time (PSADT)<=91 days, PSA value is at least 50% more than baseline value (>20 nanogram/milliliter [ng/ml] for primary radiotherapy group or >10 ng/ml for radical prostatectomy group), rescue treatment, cancer-positive biopsy, cancer-positive bone scan. (Confirmation of PSA criteria is required in an immediate subsequent PSA, if available, and PSA values for consideration are restricted to treatment period, typically up to 24-month evaluations.)	up to 28 months	No
Secondary	Number of Participants With Disease Progression	Disease progression is defined as the first occurrence of any of the following: PSADT<=91 days, PSA value is at least 50% more than baseline value (>20 ng/ml for primary radiotherapy group or >10 ng/ml for radical prostatectomy group), rescue treatment, cancer-positive biopsy, cancer-positive bone scan. If one of the PSA criteria is qualifying (within treatment period, typically up to 24-month evaluations), an immediate subsequent PSA, if available, must confirm either criterion (or at least 85% of the qualifying value).	up to 28 months	No
Secondary	Number of Participants Classified as Treatment Responders at Months 3, 6, 9, 12, 15, 18, 21, and 24	Treatment responders at Month X were defined as participants (par.) with either a PSA decrease or an increase <=15% from baseline to Month X confirmed in all PSA measurements between baseline (BL) and Month X.	Months 3, 6, 9, 12, 15, 18, 21, and 24	No
Secondary	Time to PSA Rise From Baseline (in Days)	A participant was designated as having a PSA rise if there existed a post-baseline PSA value (within treatment period, typically up to 24-month evaluations) that was >1.15 times the baseline PSA value, and all subsequent PSA values were >1.15 times the baseline PSA value. The study day for the first PSA evaluation that qualified for analysis of PSA rise was used for time to PSA rise. If none of the post-baseline PSA values qualified for analysis of PSA rise during the study, time to PSA rise was censored at the last post-baseline PSA evaluation.	up to 28 months	No
Secondary	Number of Participants With a PSA Rise From Baseline	A participant was designated as having a PSA rise if there existed a post-baseline PSA value (within treatment period, typically up to 24-month evluations) that was >1.15 times the baseline PSA value, and all subsequent PSA values were >1.15 times the baseline PSA value.	up to 28 months	No
Secondary	Time to PSA Progression (in Days)	A participant was designated as having PSA progression if there existed a post-baseline PSA value (within treatment period, typically up to 24-month evaluations) that was >10 ng/ml if radical prostatectomy or >20 ng/ml if primary radiotherapy and PSA >=1.5 times the baseline PSA value, or 0	up to 28 months	No
Secondary	Number of Participants With PSA Progression	A participant was designated as having a PSA progression if there existed a post-baseline PSA value (within treatment period, typically up to 24-month evaluations) that was (>10 ng/ml if radical prostatectomy or >20 ng/ml if primary radiotherapy) and PSA >=1.5 times the baseline PSA value), or 0	up to 28 months	No
Secondary	Change in Total PSA From Baseline at Months 12 and 24	Change in PSA from baseline at Month X = Month X PSA - Baseline PSA. The missing PSA value for scheduled visits could have been replaced by non-missing PSA values within 30 days after the clinic visit date. If such replacement was not possible, the latest non-missing post-baseline PSA before the scheduled visit was used for the scheduled visit PSA (Last Observation Carried Forward).	Baseline; Months 12 and 24	No
Secondary	Percent Change in Total PSA From Baseline at Months 12 and 24	Percent change in PSA from baseline at Month X = 100*(Month X PSA - Baseline PSA)/Baseline PSA. The missing PSA value for scheduled visits could have been replaced by non-missing PSA values within 30 days after the clinic visit date. If such replacement was not possible, the latest non-missing post-baseline PSA before the scheduled visit was used for the scheduled visit PSA (Last Observation Carried Forward).	Baseline; Months 12 and 24	No
Secondary	Change in PSA From Nadir PSA at Months 12 and 24	Change from nadir PSA at Month X = Month X PSA - nadir PSA. Nadir PSA was reported by the site as the lowest historical PSA value after the radical therapy. A nadir value below the detection level was captured as 0.0. The missing PSA value for scheduled visits could have been replaced by non-missing PSA values within 30 days after the clinic visit date. If such replacement was not possible, the latest non-missing post-baseline PSA before the scheduled visit was used for the scheduled visit PSA (Last Observation Carried Forward).	Baseline; Months 12 and 24	No
Secondary	Percent Change in PSA From Nadir PSA at Months 12 and 24	Percent change from nadir PSA at Month X = 100*(Month X PSA - nadir PSA)/Nadir PSA. Nadir PSA was reported by the site as the lowest historical PSA value after the radical therapy. A nadir value below the detection level was captured as 0.0. The missing PSA value for scheduled visits could have been replaced by non-missing PSA values within 30 days after the clinic visit date. If such replacement was not possible, the latest non-missing post-baseline PSA before the scheduled visit was used for the scheduled visit PSA (Last Observation Carried Forward).	Baseline; Months 12 and 24	No
Secondary	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)	Participants with improvement included those whose PSADT at a specified visit was positive but more than the baseline PSADT, whose PSA at the visit was the same as the baseline PSA, or whose PSA at the visit was less than the baseline PSA. Participants with worsening included those whose PSADT at the visit was positive but less than the baseline PSADT.	Baseline; Month 12, Month 24, End-of-Treatment (up to 28 months)	No
Secondary	Changes From Baseline in Disease-related Anxiety Measured by the Memorial Anxiety Scale for Prostate Cancer (MAX-PC)	MAX-PC is an 18-item, self-reported measure that evaluates prostate cancer-related anxiety. The score ranges from 0 to 54, and an increase in the score indicates a worsened anxiety level. Change from Baseline at Month X = Month X MAX-PC score - Baseline MAX-PC score. A missing post-baseline value is replaced by the last available post-baseline value (Last Observation Carried Forward(LOCF)). A general linear model controls for previous therapy, site cluster, and baseline MAX-PC score.	Baseline; Months 3, 6, 12, 18, and 24	No
Secondary	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	A participant has a normal value for a laboratory parameter if the value is within the low and high range of normal provided by the laboratory. Each laboratory parameter is evaluated for shift from normal at baseline to abnormal any time post-baseline. A participant with any laboratory parameter showing this shift is counted. A participant is counted only once even if he had such a shift in more than one laboratory parameter or more than once among all post-baseline evaluations.	Baseline; up to 28 months	Yes
Secondary	Number of Participants With a Threshold Laboratory Value for Any Parameter at Baseline (BL) and Any Time Post-baseline	Threshold laboratory values are defined in terms of a multiplicative factor of the testing laboratory's normal range, pre-specified in the analysis plan. A laboratory value that is above the upper limit factor multiplied by the upper limit of the normal range is considered a high threshold value. A laboratory value that is below the lower limit factor multiplied by the lower limit of the normal range is considered a low threshold value.	Baseline; up to 28 months	Yes
Secondary	Number of Participants With Palpable Breast Tissue (PBT) at Baseline (BL) and Any Time Post-baseline	Participants underwent clinical examination of the breasts, to evaluate for palpable breast tissue. Clinical significance of the results was determined by subjective judgment of the clinical personnel performing the examination.	Baseline; up to 28 months	Yes
Secondary	Number of Participants With Nipple Tenderness (NT) at Baseline (BL) and Any Time Post-baseline	Participants underwent clinical examination of the breasts, to evaluate for nipple tenderness. Clinical significance of the results was determined by subjective judgment of the clinical personnel performing the examination.	Baseline; up to 28 months	Yes
Secondary	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	Participants underwent a digital rectal examination to evaluate for focal abnormality of the prostate.	Baseline; up to 28 months	Yes
Secondary	Number of Participants With Threshold Vital Signs at Baseline and Any Time Post-baseline	Threshold vital signs are defined as follows: < 80 mmHg or > 165 mmHg for systolic blood pressure; < 40 mmHg or > 105 mm Hg for diastolic blood pressure, < 40 beats per minute (bpm) or > 100 bpm for heart rate.	Baseline; up to 28 months	Yes