A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Apalutamide in Subjects With High-risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 2,517
- 试验地点
- 379
- 主要终点
- Percentage of Participants with Pathologic complete response (pCR)
研究概览
简要总结
The purpose of this study is to determine if treatment with apalutamide plus androgen deprivation therapy (ADT) before and after radical prostatectomy (RP) with pelvic lymph node dissection (pLND) in participants with high-risk localized or locally advanced prostate cancer results in an improvement in pathological complete response (pCR) rate and metastasis-free survival (MFS) as compared to placebo plus ADT.
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 confirmed adenocarcinoma of the prostate
- •High-risk disease defined by a total Gleason Sum Score greater than equal to (>=) 4+3 (=Grade Groups [GG] 3-5) and >=1 of the following 4 criteria: a) Any combination of Gleason Score 4+3 (= 3) and Gleason Score 8 (4+4 or 5+3) in >= 6 systematic cores (with >=1 core Gleason Score 8 [4+4 or 5+3] included); b) Any combination of Gleason Score 4+3 (=GG 3) and Gleason Score 8 (4+4 or 5+3) in >=3 systematic cores and Prostate-specific antigen (PSA) >=20 ng/mL (with >= 1 core Gleason Score 8 [4+4 or 5+3] included); c) Gleason Score >=9 (=GG 5) in at least 1 systematic or targeted core; d) At least 2 systematic or targeted cores with continuous Gleason Score >=8 (=GG 4), each with > 80 percent (%) involvement
- •Candidate for radical prostatectomy with pelvic lymph node dissection as per the investigator
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- •Contraceptive use by male participants (and female partners of male participants enrolled in the study who are of childbearing potential or are pregnant) should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
- •Able to receive androgen deprivation therapy (ADT) for at least 13 months
排除标准
- •Distant metastasis based on conventional imaging (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal disease (clinical N stage; N1 versus N0) will be assessed by central radiological review. Participants are considered eligible only if the central radiological review confirms clinical stage M0
- •(a) Prior treatment with androgen receptor antagonists; (b) Treatment with gonadotropin-releasing hormone analog (GnRHa) prior to informed consent form (ICF) signature
- •History of prior systemic or local therapy for prostate cancer, including pelvic radiation for prostate cancer
- •Use of any investigational agent less than or equals to (<=)4 weeks prior to randomization or any therapeutic procedure for prostate cancer at any time
- •Major surgery <=4 weeks prior to randomization
- •Any of the following within 12 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (example, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary
研究组 & 干预措施
Apalutamide + ADT
Participants will receive androgen deprivation therapy (ADT) plus oral administration of apalutamide 240 milligram (mg) (4 tablets of 60 mg each) daily in each cycle (each cycle of 28 days). Participants will receive six cycles of treatment, followed by radical prostatectomy (RP) with pelvic lymph node dissection (pLND), followed by an additional six cycles of treatment. A Long-Term Extension (LTE) may be initiated at sponsor's discretion after completion of the primary endpoint analysis.
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
Placebo + ADT
Participants will receive ADT with oral administration of matching placebo treatment daily in each cycle (each cycle of 28 days). Participants will receive six cycles of placebo treatment, followed by RP with pLND, followed by an additional six cycles of placebo treatment. A LTE may be initiated at sponsor's discretion after completion of the primary endpoint analysis.
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
Placebo + ADT
Participants will receive ADT with oral administration of matching placebo treatment daily in each cycle (each cycle of 28 days). Participants will receive six cycles of placebo treatment, followed by RP with pLND, followed by an additional six cycles of placebo treatment. A LTE may be initiated at sponsor's discretion after completion of the primary endpoint analysis.
干预措施: Placebo (Drug)
Apalutamide + ADT
Participants will receive androgen deprivation therapy (ADT) plus oral administration of apalutamide 240 milligram (mg) (4 tablets of 60 mg each) daily in each cycle (each cycle of 28 days). Participants will receive six cycles of treatment, followed by radical prostatectomy (RP) with pelvic lymph node dissection (pLND), followed by an additional six cycles of treatment. A Long-Term Extension (LTE) may be initiated at sponsor's discretion after completion of the primary endpoint analysis.
干预措施: Apalutamide (Drug)
结局指标
主要结局
Percentage of Participants with Pathologic complete response (pCR)
时间窗: Approximately 4 years
pCR is assessed by a pathology blinded independent central radiology review (BICR) as defined in the pathology charter.
Metastasis-Free Survival (MFS)
时间窗: Up to 7 years and 5 months
MFS is defined as the time from randomization to the date of the occurrence of radiographic distant metastasis evaluated by radiology BICR, incidental pathologic finding of distant metastasis, or death from any cause, whichever occurs first.
Percentage of Participants with Pathologic complete response (pCR)
时间窗: Approximately 4 years
pCR is assessed by a pathology blinded independent central radiology review (BICR) as defined in the pathology charter.
Metastasis-Free Survival (MFS)
时间窗: Up to 7 years and 5 months
MFS is defined as the time from randomization to the date of the occurrence of radiographic distant metastasis evaluated by radiology BICR, incidental pathologic finding of distant metastasis, or death from any cause, whichever occurs first.
次要结局
- Time to Subsequent First Treatments (TTST-1)(Up to 7 years and 5 months)
- Prostate Specific Antigen (PSA)-Free Survival(Approximately 4 years)
- Event Free Survival (EFS)(Up to 7 years and 5 months)
- Number of Participants with Physical Examinations Abnormalities as a Measure of Safety and Tolerability(Up to 30 days after last dose of study drug (Approximately 8 years))
- Number of Participants with Laboratory Abnormalities as a Measure of Safety and Tolerability(Up to 30 days after last dose of study drug (Approximately 8 years))
- Number of Participants with Treatment Compliance Rate(Up to 30 days after last dose of study drug (Approximately 8 years))
- Time to Distant Metastasis (TTDM)(Up to 7 years and 5 months)
- MFS Based on Conventional Imaging(Up to 7 years and 5 months)
- Number of Participants with No Evidence of Disease (NED) at 4 Years(Up to 4 years)
- Number of Participants with Vital Signs Abnormalities as a Measure of Safety and Tolerability(Up to 30 days after last dose of study drug (Approximately 8 years))