A Phase 3, Randomized, Double-Blind Study of Nivolumab or Placebo in Combination With Docetaxel, in Men With Metastatic Castration-resistant Prostate Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,030
- 试验地点
- 293
- 主要终点
- Radiographic Progressive Free Survival (rPFS) Assessed by Blinded Independent Central Review (BICR) Per Prostate Cancer Working Group 3 (PCWG3)
研究概览
简要总结
The purpose of this study is to assess the safety and effectiveness of nivolumab with docetaxel in men with advanced castration resistant prostate cancer who have progressed after second-generation hormonal manipulation.
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)
盲法说明
Double-Blinded
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
- •Histologic confirmation of adenocarcinoma of the prostate without small cell features
- •Current evidence of metastatic disease documented by either bone lesions on radionuclide bone scan and/or soft tissue lesions on computerized tomography/magnetic resonance imaging (CT/MRI)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy
- •Documented prostate cancer progression per Prostate Cancer Working Group (PCWG3) criteria within 6 months prior to screening
- •Chemotherapy-naïve for metastatic castration-resistant prostate cancer (mCRPC), with 1 to 2 prior second generation hormonal therapies in the recurrent non-metastatic setting and/or metastatic setting, and no more than 1 second generation hormonal therapy in the mCRPC setting. Must have progressed during or after second generation hormonal therapy or have documented intolerance to second generation hormonal therapy
- •Participants must meet one of the following criteria regarding tissue submission: Sufficient tumor samples from a newly obtained ("fresh") biopsy (obtained during screening); or archival tumor tissue in the form of formalin-fixed paraffin-embedded (FFPE) block or unstained tumor tissue slides. For participants with bone-only disease or inaccessible soft tissue lesions or if the biopsy procedure would pose an unacceptable clinical risk for the participant, submission of tumor tissue obtained from a fresh biopsy is not required.
- •Men must agree to follow specific methods of contraception, if applicable
排除标准
- •Active brain metastases
- •Active, known, or suspected autoimmune disease
- •Condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids or adrenal replacement steroid doses are permitted in the absence of active autoimmune disease
- •Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- •Prior treatment with docetaxel or other chemotherapy for mCRPC. Prior docetaxel for metastatic castration-sensitive prostate cancer is permitted if at least 12 months have elapsed from last dose of docetaxel
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Arm A: Nivolumab + docetaxel + prednisone
干预措施: Nivolumab (Biological)
Arm A: Nivolumab + docetaxel + prednisone
干预措施: Prednisone (Drug)
Arm A: Nivolumab + docetaxel + prednisone
干预措施: Docetaxel (Drug)
Arm B: Placebo + docetaxel + prednisone
干预措施: Prednisone (Drug)
Arm B: Placebo + docetaxel + prednisone
干预措施: Docetaxel (Drug)
Arm B: Placebo + docetaxel + prednisone
干预措施: Placebo (Other)
结局指标
主要结局
Radiographic Progressive Free Survival (rPFS) Assessed by Blinded Independent Central Review (BICR) Per Prostate Cancer Working Group 3 (PCWG3)
时间窗: from randomization to the first date of documented progression or death due to any cause, whichever occurs first (up to approximately 31 months)
rPFS for randomized participants is the time between randomization and the first date of documented progression or death due to any cause, whichever occurs first. The rPFS was censored at the last radiographic tumor assessment up to the start of subsequent cancer therapy for those without progression or death. It was also censored at the date of last radiographic tumor assessment prior to the missed tumor assessments for participants who had progressive disease (PD) or death immediately after more than one consecutive missed tumor assessments. Radiographic progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions is also considered progression.
Overall Survival (OS)
时间窗: From randomization to the date of death from any cause (Up to approximately 31 months)
OS for all randomized participants is the time between randomization and the date of death from any cause. For participants who are alive, their survival time was censored at the last date that they were known to be alive. OS was censored for participants at the date of randomization if they had no follow-up.
次要结局
- Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) Per Prostate Cancer Working Group (PCWG3)(From date of randomization to the date of objectively documented progression per PCWG3 or the date of subsequent systemic cancer therapy, whichever occurs first (Up to approximately 52 months))
- Time to Response (TTR) Assessed by Blinded Independent Central Review (BICR) Per Prostate Cancer Working Group (PCWG3)(From randomization to the date of the first documented CR or PR (Up to approximately 52 months))
- Duration of Response Assessed by Blinded Independent Central Review (BICR) Per Prostate Cancer Working Group (PCWG3)(From randomization date to the date of first documented radiographic progression or death due to any cause whichever occurs first (Up to approximately 52 months))
- Prostate-specific Antigen (PSA) Response Rate (PSA-RR)(Up to approximately 52 months)
- Time to PSA Progression (TTP-PSA)(from randomization to the date of PSA Progression (Up to approximately 31 months))
- Number of Participants With Adverse Events(From first dose and 30 days after last dose of study therapy (Up to approximately 25 months))
- Number of Participants With Serious Adverse Events(From first dose and 30 days after last dose of study therapy (Up to approximately 25 months))
- Number of Participants With Adverse Events Leading to Discontinuation(From first dose and 30 days after last dose of study therapy (Up to approximately 25 months))
- Number of Participants With Endocrine Immune-Mediated Adverse Events(From first dose and 100 days after last dose of study therapy (Up to approximately 13 months))
- Number of Participants With Non-Endocrine Immune-Mediated Adverse Events(From first dose and 100 days after last dose of study therapy (Up to approximately 13 months))
- Number of Participants With Select Adverse Events(From first dose and 30 days after last dose of study therapy (Up to approximately 25 months))
- Number of Participants Who Died(Up to approximately 52 months)
- Number of Participants With Worst Common Terminology Criteria (CTC) Grade Laboratory Test Grade Change From Baseline(From first dose and 30 days after last dose of study therapy (Up to approximately 25 months))
- Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests(From first dose and 30 days after last dose of study therapy (Up to approximately 11 months))
- Time to Pain Progression as Assessed by Brief Pain Inventory-Short Form (BPI-SF)(From randomization to 1st pain symptoms at their worst over the last 24 hours (Up to approximately 31 months)