A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase IV Study of Apalutamide in Chinese Participants With Non-Metastatic Castration-Resistant Prostate Cancer (NM-CRPC)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 42
- 主要终点
- Time to Prostate Specific Antigen (PSA) Progression (TTPP) Based on Prostate Cancer Working Group 2 (PCWG2) Criteria
研究概览
简要总结
The purpose of this study is to compare the improvement in time to prostate specific antigen (PSA) progression (TTPP, as defined by Prostate Cancer Working Group 2 [PCWG2]) of apalutamide versus placebo in Chinese participants with high-risk non-metastatic castration resistant prostate cancer (NM-CRPC).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features, with high risk for development of metastases, defined as prostate-specific antigen doubling time (PSADT) less than or equals to (<=) 10 months. PSADT is calculated using at least 3 prostate-specific antigen (PSA) values obtained during continuous androgen deprivation therapy (ADT)
- •Castration-resistant prostate cancer (PC) demonstrated during continuous ADT, defined as 3 PSA rises at least 1 week apart, with the last PSA greater than (>) 2 nanogram per milliliter (ng/mL)
- •Surgically or medically castrated, with testosterone levels of less than (<) 50 nanogram per deciliter (ng/dL). If the participant is medically castrated, continuous dosing with gonadotropin releasing hormone analog (GnRHa) must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study to maintain castrate levels of testosterone
- •Participants who received a first-generation anti-androgen (example: bicalutamide, flutamide, nilutamide) must have at least a 4-week washout prior to randomization and must show continuing disease progression (an increase in PSA) after washout
- •At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization
排除标准
- •Presence of distant metastases, including central nervous system (CNS) and vertebral or meningeal involvement, or history of distant metastases. Exception: Pelvic lymph nodes <2 centimeter in short axis (N1) located below the iliac bifurcation are allowed
- •Symptomatic loco-regional disease requiring medical intervention, such as moderate or severe urinary obstruction or hydronephrosis, due to primary tumor (example, tumor obstruction of bladder trigone)
- •Prior treatment with cytochrome P450 17 alpha-hydroxylase/17,20-lyase (CYP17) inhibitors (example: abiraterone acetate, orteronel, galerterone, ketoconazole, aminoglutethimide) for PC
- •Prior chemotherapy for PC, except if administered in the adjuvant/neoadjuvant setting
- •Prior treatment with second generation anti-androgens (example, enzalutamide)
- •History of seizure or condition that may pre-dispose to seizure (example: prior stroke within 1 year prior to randomization, brain arteriovenous malformation, schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)
研究组 & 干预措施
Apalutamide 240 milligram (mg) plus ADT
Participants will receive apalutamide 240 mg orally daily from Day 1 of Cycle 1 until disease progression, unacceptable toxicity, withdrawal of consent, death or termination of the study along with androgen-deprivation therapy (ADT). Each treatment cycle will consist of 28 days.
干预措施: Apalutamide (Drug)
Apalutamide 240 milligram (mg) plus ADT
Participants will receive apalutamide 240 mg orally daily from Day 1 of Cycle 1 until disease progression, unacceptable toxicity, withdrawal of consent, death or termination of the study along with androgen-deprivation therapy (ADT). Each treatment cycle will consist of 28 days.
干预措施: Androgen-deprivation Therapy (ADT) (Drug)
Placebo plus ADT
Participants will receive matching placebo daily along with ADT from Cycle 1 Day 1 until disease progression, unacceptable toxicity, withdrawal of consent, death or termination of the study. Participants who do not have distant metastasis will switch to treatment with apalutamide after completion of 5 cycles of placebo treatment. Participants who have prostate-specific antigen (PSA) progression prior to completion of 5 cycles of study treatment, will cross over to apalutamide at the time of PSA progression. Each treatment cycle will consist of 28 days.
干预措施: Placebo (Drug)
Placebo plus ADT
Participants will receive matching placebo daily along with ADT from Cycle 1 Day 1 until disease progression, unacceptable toxicity, withdrawal of consent, death or termination of the study. Participants who do not have distant metastasis will switch to treatment with apalutamide after completion of 5 cycles of placebo treatment. Participants who have prostate-specific antigen (PSA) progression prior to completion of 5 cycles of study treatment, will cross over to apalutamide at the time of PSA progression. Each treatment cycle will consist of 28 days.
干预措施: Androgen-deprivation Therapy (ADT) (Drug)
结局指标
主要结局
Time to Prostate Specific Antigen (PSA) Progression (TTPP) Based on Prostate Cancer Working Group 2 (PCWG2) Criteria
时间窗: From randomization until first documented PSA progression (up to 3 years 3 months)
Time to prostate specific antigen progression (TTPP) was defined as the time from randomization to the first date of documented PSA progression based on PCWG2 criteria. PCWG2 was defined as the PSA progression as 1) the date that a 25 percent (%) or greater increase and an absolute increase of 2 nanograms per milliliter (ng/mL) or more from the Nadir was documented, which was confirmed by a second value obtained 3 or more weeks later. 2) Where no decline from baseline was documented as a 25% increase from the baseline value along with an increase in absolute value of 2 ng/mL or more after 12 week of treatment. Kaplan-Meier method was used for the analysis.
次要结局
- Plasma Concentration of Apalutamide and Its Metabolite (N-desmethyl Apalutamide)(Presdose: Day 1 of Cycles 1, 2, 3, and 6; 2 hours postdose: Day 1 of Cycles 1 and 3)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(Up to 6 years 4 months)
- Number of Participants With Grade 3 or Higher Abnormalities in Laboratory Values(Up to 6 years 4 months)
- Percentage of Participants Who Achieved Prostate Specific Antigen (PSA) Response (>=50% PSA Reduction)(Up to 6 years 4 months)