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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 294
- 试验地点
- 1
- 主要终点
- Time to Prostate-specific Antigen (PSA) Doubling From Baseline (in Days)
研究概览
简要总结
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.
详细描述
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
- •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.
排除标准
- •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
研究组 & 干预措施
Avodart
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.
干预措施: Avodart (Drug)
Placebo Arm
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.
干预措施: placebo (Other)
结局指标
主要结局
Time to Prostate-specific Antigen (PSA) Doubling From Baseline (in Days)
时间窗: up to 28 months
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.
Number of Participants With PSA Doubling From Baseline
时间窗: up to 28 months
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.
Time to PSA Doubling From Baseline (in Days) Within Year 1
时间窗: up to 16 months
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.
Number of Participants With PSA Doubling From Baseline During Year 1
时间窗: up to 16 months
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.
次要结局
- 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)
- Number of Participants With Threshold Vital Signs at Baseline and Any Time Post-baseline(Baseline; up to 28 months)
- 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)