A Randomized, Open Label, Multicenter Study of Cabazitaxel Versus an Androgen Receptor (AR)-Targeted Agent (Abiraterone or Enzalutamide) in mCRPC Patients Previously Treated With Docetaxel and Who Rapidly Failed a Prior AR-targeted Agent (CARD)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 255
- 试验地点
- 65
- 主要终点
- Radiographic Progression-Free Survival (rPFS)
研究概览
简要总结
Primary Objective:
To compare the radiographic progression-free survival (rPFS) (using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 for tumor lesions and Prostate Cancer Working Group 2 (PCWG2) criteria for bone scan lesions or death due to any cause) with chemotherapy (cabazitaxel plus prednisone, Arm A) versus Androgen Receptor (AR)-targeted therapy (enzalutamide or abiraterone acetate plus prednisone, Arm B) in mCRPC participants who have been treated with docetaxel and who had disease progression while receiving AR-targeted therapy within 12 months of AR treatment initiation (less than or equal to [<=]12 months, either before or after docetaxel).
Secondary Objective:
- To compare efficacy for:
- Prostate-specific antigen (PSA) response rate and time to PSA progression (TTPP).
- Progression-free survival (PFS).
- Overall survival (OS).
- Tumor response rate and duration of tumor response.
- Pain response and time to pain progression.
- Symptomatic skeletal event (SSE) rate and time to occurrence of any SSE.
- Health status and Health-related Quality of Life (HRQOL).
- To evaluate the correlation of a signature of resistance to AR-targeted agents with clinical outcome via the analysis of circulating tumor cell (CTC) phenotypes as well as expression and localization of proteins including AR isoforms in CTCs.
- To evaluate safety in the 2 treatment arms.
详细描述
The duration of the study per participant was approximately 2 years. Each participant was treated until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment, and each participant was followed after completion of study treatment until death, study cut-off date, or withdrawal of participant consent.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cabazitaxel
Participants received Cabazitaxel 25 mg/m^2 intravenous (IV) infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic granulocyte-colony stimulating factor (G-CSF) as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).
干预措施: cabazitaxel XRP6258 (Drug)
Cabazitaxel
Participants received Cabazitaxel 25 mg/m^2 intravenous (IV) infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic granulocyte-colony stimulating factor (G-CSF) as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).
干预措施: prednisone (Drug)
Abiraterone acetate or enzalutamide
Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
干预措施: enzalutamide (Drug)
Abiraterone acetate or enzalutamide
Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
干预措施: abiraterone acetate (Drug)
Abiraterone acetate or enzalutamide
Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
干预措施: prednisone (Drug)
结局指标
主要结局
Radiographic Progression-Free Survival (rPFS)
时间窗: From randomization until tumor progression or bone lesion progression, death due to any cause, or data cut-off date whichever comes first (maximum duration: up to 141 weeks)
Radiographic progression-free survival: time (in months) from randomization to occurrence of any one of following: radiological tumor progressions using response evaluation criteria in solid tumors (RECIST 1.1), progression of bone lesions using Prostate Cancer Working Group 2 (PCWG2) criteria or occurrence of death due to any cause. Progression as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Progression of bone lesions (PCWG2 criteria): first bone scan with \>= 2 new lesions compared to Baseline observed less than (\<) 12 weeks from randomization and confirmed by a second bone scan performed \>=6 weeks; first bone scan with \>=2 new lesions compared to Baseline observed \>=12 weeks from randomization. In accordance with protocol, data cut-off date for final analysis of this endpoint was the date when 196 rPFS events had occurred. Analysis done by Kaplan-Meier method.
次要结局
- Overall Survival (OS)(From randomization to death due to any cause, or data cut-off date whichever comes first (maximum duration: up to 141 weeks))
- Progression Free Survival (PFS)(From randomization until tumor progression or bone lesion progression, pain progression, death due to any cause, or data cut-off date whichever comes first (maximum duration: up to 141 weeks))
- Percentage of Participants With Prostate Specific Antigen (PSA) Response(Baseline up to PSA response, death due to any cause or data cut-off date whichever comes first (maximum duration: up to 141 weeks))
- Percentage of Participants With Overall Objective Tumor Response(From randomization until disease progression, death due to any cause or data cut-off date whichever comes first (maximum duration: up to 141 weeks))
- Time to PSA Progression (TTPP)(From time from randomization until PSA progression, death due to any cause or data cut-off whichever comes first (maximum duration: up to 141 weeks))
- Duration of Tumor Response(From the date of the first response to the date of first documented tumor progression, or death due to any cause or data cut-off date whichever comes first (maximum duration: up to 141 weeks))
- Percentage of Participants Achieving Pain Response Assessed Using Brief Pain Inventory-Short Form (BPI-SF) Pain Intensity Score(Baseline until pain progression, first further anticancer therapy, or data cut-off whichever comes first (maximum duration: up to 141 weeks))
- Time to Pain Progression(Baseline until pain progression or data cut-off whichever comes first (maximum duration: up to 141 weeks))
- Number of Symptomatic Skeletal Events (SSE)(Baseline until occurrence of first SSE or data cut-off, whichever comes first (maximum duration: up to 141 weeks))
- Time to Symptomatic Skeletal Event(From date of randomization until first SSE, or data cut-off whichever comes first (maximum duration: up to 141 weeks))
- Health-Related Quality of Life (HRQOL): Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score at Cycle 2, 3, 4, 5, 6, 7, 8 and End of Treatment(Baseline, Day 1 of each Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 6, Cycle 7, Cycle 8 and at End of Treatment (any time up to 141 weeks))
- Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Utility Single Index and Visual Analogue Scale (VAS) Scores at Cycle 2, 3, 4, 5, 6, 7, 8 and End of Treatment(Baseline, Day 1 of each Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 6, Cycle 7, Cycle 8 and at End of Treatment (any time up to: 141 weeks))
- Radiographic Progression-Free Survival (rPFS) in Participants With Presence and Absence of Biomarker(From randomization until tumor progression or bone lesion progression, death due to any cause, or data cut-off date whichever comes first (maximum duration: up to 141 weeks))