A Randomized Phase IV Study Comparing Enzalutamide Versus Flutamide in Castration-resistant Prostate Cancer (CRPC) Patients Who Have Failed Combined Androgen Blockade Therapy With Bicalutamide Plus Androgen Deprivation Therapy (ADT)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 206
- 试验地点
- 47
- 主要终点
- Time to PSA Progression With 1st Line AAT (TTPP1)
研究概览
简要总结
The objective of this study was to compare the efficacy and safety of the combination therapy with enzalutamide + androgen deprivation therapy (ADT) and the combination therapy with flutamide + ADT in patients with castration resistant prostate cancer who had relapsed during combined androgen blockade (CAB) therapy with bicalutamide and ADT. This study also investigated the order of alternative antiandrogen therapy (AAT) by changing the 1st line medication after relapse of prostate-specific antigen (PSA).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Subject is diagnosed with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small-cell histology.
- •Subject on continuous ADT with Gonadotropin Releasing Hormone (GnRH) agonist/antagonist or bilateral orchiectomy.
- •Serum testosterone level below the target level at screening visit.
- •Subject with asymptomatic or mildly symptomatic prostate cancer.
- •Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Subject has progression of the disease as defined by rising PSA levels or progressive soft tissue or bony disease during CAB therapy in combination of bicalutamide and ADT.
- •A sexually active male subject and the subject's female partner who is of childbearing potential must use 2 acceptable birth control methods from screening to 3 months after the last dose of the study drug.
- •Subject must agree not to donate sperm from screening to 3 months after the last dose of the study drug.
排除标准
- •Subject with severe concurrent diseases, infections, or complications.
- •Subject with confirmed or suspected brain metastasis or active leptomeningeal metastasis.
- •Subject with a history of malignant tumor other than prostate cancer in the past 5 years.
- •Subject hypersensitive to the ingredients of enzalutamide capsules or flutamide tablets.
- •Subject with a history of convulsive attack, or prone to convulsive attack.
- •Subject with liver disorder such as viral hepatitis and hepatic cirrhosis, or subject with Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) at screening visit higher than the upper limit of normal.
- •Subject received treatment for prostate cancer with cytocidal chemotherapy that includes anti androgenic agents other than bicalutamide, abiraterone, or estramustine.
研究组 & 干预措施
Enzalutamide 160 mg 1st line AAT/Flutamide 375 mg 2nd line AAT
Participants received enzalutamide 160 mg capsules, orally once daily as 1st line of alternative antiandrogen therapy (AAT) until confirmed prostate-specific antigen (PSA) progression, other disease progression, or an intolerable adverse event. After confirmation of PSA progression, other disease progression, or an intolerable adverse event, participants received flutamide 125 mg tablets orally thrice daily after each meal as 2nd line of AAT. Treatment with each drug was continued until the participant met any of the discontinuation criteria or until 2 years from the enrollment of the last participant (approximately 38 months).
干预措施: Enzalutamide (Drug)
Enzalutamide 160 mg 1st line AAT/Flutamide 375 mg 2nd line AAT
Participants received enzalutamide 160 mg capsules, orally once daily as 1st line of alternative antiandrogen therapy (AAT) until confirmed prostate-specific antigen (PSA) progression, other disease progression, or an intolerable adverse event. After confirmation of PSA progression, other disease progression, or an intolerable adverse event, participants received flutamide 125 mg tablets orally thrice daily after each meal as 2nd line of AAT. Treatment with each drug was continued until the participant met any of the discontinuation criteria or until 2 years from the enrollment of the last participant (approximately 38 months).
干预措施: Flutamide (Drug)
Enzalutamide 160 mg 1st line AAT/Flutamide 375 mg 2nd line AAT
Participants received enzalutamide 160 mg capsules, orally once daily as 1st line of alternative antiandrogen therapy (AAT) until confirmed prostate-specific antigen (PSA) progression, other disease progression, or an intolerable adverse event. After confirmation of PSA progression, other disease progression, or an intolerable adverse event, participants received flutamide 125 mg tablets orally thrice daily after each meal as 2nd line of AAT. Treatment with each drug was continued until the participant met any of the discontinuation criteria or until 2 years from the enrollment of the last participant (approximately 38 months).
干预措施: Androgen deprivation therapy (Other)
Flutamide 375 mg 1st line AAT/Enzaltumide 160 mg 2nd line AAT
Participants received flutamide 125 mg tablets orally thrice daily after each meal as 1st line of AAT until confirmed PSA progression, other disease progression, or an intolerable adverse event. After confirmed PSA progression, other disease progression, or an intolerable adverse event. participants received enzalutamide 160 mg capsules orally once daily as 2nd line of AAT. Treatment with each drug was continued until the participant met any of the discontinuation criteria or until 2 years from the enrollment of the last participant (approximately 38 months).
干预措施: Enzalutamide (Drug)
Flutamide 375 mg 1st line AAT/Enzaltumide 160 mg 2nd line AAT
Participants received flutamide 125 mg tablets orally thrice daily after each meal as 1st line of AAT until confirmed PSA progression, other disease progression, or an intolerable adverse event. After confirmed PSA progression, other disease progression, or an intolerable adverse event. participants received enzalutamide 160 mg capsules orally once daily as 2nd line of AAT. Treatment with each drug was continued until the participant met any of the discontinuation criteria or until 2 years from the enrollment of the last participant (approximately 38 months).
干预措施: Flutamide (Drug)
Flutamide 375 mg 1st line AAT/Enzaltumide 160 mg 2nd line AAT
Participants received flutamide 125 mg tablets orally thrice daily after each meal as 1st line of AAT until confirmed PSA progression, other disease progression, or an intolerable adverse event. After confirmed PSA progression, other disease progression, or an intolerable adverse event. participants received enzalutamide 160 mg capsules orally once daily as 2nd line of AAT. Treatment with each drug was continued until the participant met any of the discontinuation criteria or until 2 years from the enrollment of the last participant (approximately 38 months).
干预措施: Androgen deprivation therapy (Other)
结局指标
主要结局
Time to PSA Progression With 1st Line AAT (TTPP1)
时间窗: From date of randomization to the date of PSA progression in the 1st line AAT period (Up to 38 months)
TTPP1 was defined as the period from the date of randomization to the date of PSA progression in the 1st line AAT period. PSA progression was defined according to the consensus guidelines of prostate cancer clinical trials working group 2 (PCWG2). For participants with PSA declines at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir were documented, which was confirmed by a second consecutive value obtained 3 or more weeks later. For participants with no PSA decline at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline were documented. Time to event analysis was performed using kaplan-meier (KM) estimates.
次要结局
- Time to Treatment Failure of 2nd Line AAT (TTF2)(From date of randomization to discontinuation of 2nd line AAT (Up to 38 months))
- Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT(Baseline and week 13)
- Time to PSA Progression With 2nd Line AAT (TTPP2)(From date of randomization to the date of PSA progression in 2nd line AAT (Up to 38 months))
- Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT(Baseline and at least 3 weeks after, the lowest PSA decreased by at least 50% or 90% from baseline (Up to 38 months))
- Time to PSA Decrease by 50% From Baseline With 1st Line AAT(From date of randomization to the day when the decrease of PSA from baseline by 50% is first identified (Up to 38 months))
- Time to Treatment Failure of 1st Line AAT (TTF1)(From date of randomization to discontinuation of 1st line AAT (Up to 38 months))
- Radiographic Progression-free Survival (rPFS)(From date of randomization to the time when radiographic disease progression is observed or death of any cause (up to 38 months))