A Phase I/II Study of Cabazitaxel Combined With Abiraterone Acetate and Prednisone in Patients With Metastatic Castrate-Resistant Prostate Cancer (CRPC) Whose Disease Has Progressed After Docetaxel Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 38
- 试验地点
- 4
- 主要终点
- Phase 1: Maximally Tolerated Dose (MTD) of Cabazitaxel in Combination With Abiraterone Acetate
研究概览
简要总结
Primary Objectives:
- To determine the maximum tolerated dose, and dose limiting toxicities of cabazitaxel administered as a 1-hour infusion every 3 weeks in combination with oral daily abiraterone acetate and prednisone in participants with metastatic Castrate-resistant prostate cancer (CRPC)
- To estimate the anti-tumor activity of cabazitaxel in combination with abiraterone acetate and prednisone in terms of prostate-specific antigen (PSA) response rate.
Secondary Objectives:
- To characterize the safety profile of the combination
- To evaluate the pharmacokinetic profile of cabazitaxel and abiraterone in the proposed combination and dosing schedule
- To assess preliminary antitumor activity of the combination in terms of progression-free survival, PSA progression free survival and objective response rate, and overall survival
详细描述
The study duration was to include a period for inclusion of up to 3 weeks and a 3-week treatment cycle(s). The participants might continue treatment until disease progression, unacceptable toxicity or willingness to stop followed by a minimum of 30-day follow-up
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg
Cabazitaxel 20 mg/m^2 intravenous (IV) infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal.
干预措施: Cabazitaxel XRP6258 (Drug)
Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg
Cabazitaxel 20 mg/m^2 intravenous (IV) infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal.
干预措施: Abiraterone acetate (Drug)
Phase 1: Cabazitaxel 20 mg/m^2 + Abiraterone 1000 mg
Cabazitaxel 20 mg/m^2 intravenous (IV) infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal.
干预措施: Prednisone 5 mg (Drug)
Phase 1: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg
Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal.
干预措施: Cabazitaxel XRP6258 (Drug)
Phase 1: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg
Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal.
干预措施: Abiraterone acetate (Drug)
Phase 1: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg
Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal.
干预措施: Prednisone 5 mg (Drug)
Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg
Cabazitaxel at maximum tolerated dose (MTD) as determined in phase 1 part (25 mg/m^2) IV infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal.
干预措施: Cabazitaxel XRP6258 (Drug)
Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg
Cabazitaxel at maximum tolerated dose (MTD) as determined in phase 1 part (25 mg/m^2) IV infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal.
干预措施: Abiraterone acetate (Drug)
Phase 2: Cabazitaxel 25 mg/m^2 + Abiraterone 1000 mg
Cabazitaxel at maximum tolerated dose (MTD) as determined in phase 1 part (25 mg/m^2) IV infusion on Day 1 of each 21-day cycle in combination with abiraterone acetate 1000 mg orally once daily and prednisone 5 mg orally twice daily until disease progression, unacceptable toxicity or consent withdrawal.
干预措施: Prednisone 5 mg (Drug)
结局指标
主要结局
Phase 1: Maximally Tolerated Dose (MTD) of Cabazitaxel in Combination With Abiraterone Acetate
时间窗: Up to Cycle 2 of Phase 1 (up to 42 days)
MTD was defined as highest dose level of cabazitaxel in combination with abiraterone acetate at which no more than 1 participant experienced dose limiting toxicities (DLT). DLT was defined as any of the following events related to study treatment: 1) Grade 3 or 4 non-hematological related adverse event with exception of Grade 3 fever without documented infection; Grade 3 nausea, vomiting, or diarrhea in the absence of effective maximal therapy; and Grade 3 hypersensitivity reaction in the absence of required premedication. 2) Hematological toxicity: Febrile neutropenia (fever of unknown origin ≥38.5°C with neutropenia Grade 3 or 4); Neutropenia Grade 4 lasting \>7 days; Thrombocytopenia Grade 4 or Grade 3 complicated by hemorrhage. 3) Re-treatment delay of more than 2 weeks due to delayed recovery from a toxicity related to study treatment to baseline or ≤ Grade 1 (except for alopecia). Grades were based on National Cancer Institute CommonTerminology Criteria for Adverse Events v4.03.
Phase 2: Percentage of Participants With Prostate Specific Antigen (PSA) Response
时间窗: Baseline, every 3 weeks up to PSA progression (maximum duration: 603 days)
Prostate specific antigen (PSA) response was defined as ≥50% decrease from baseline in serum PSA levels, confirmed at least 3 weeks later. Increases of any magnitude during the first 12 weeks were ignored in determining PSA response. PSA was to be measured at baseline, every 3 weeks, throughout study period, until progression. PSA progression was defined as: -An increase of 25% above the nadir (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have achieved a ≥50% decline of PSA. -An increase in PSA by 25 % above the baseline level (at least 2 ng/mL), confirmed by a second PSA value at least 3 weeks apart, in participants who have not achieved a ≥50% decline of PSA.
次要结局
- Phase 2: PSA Progression Free Survival(Baseline, every 3 weeks up to PSA progression (maximum duration: 603 days))
- Phase 2: Objective Progression Free Survival (PFS)(From baseline until radiological tumor or disease progression or death due to any cause, assessed up to Month 5)
- Phase 2: Pharmacokinetic of Cabazitaxel : Maximum Plasma Concentration Observed (Cmax)(5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1)
- Phase 2: Pharmacokinetic of Cabazitaxel : Terminal Half-life (t 1/2z)(5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1)
- Phase 2: Pharmacokinetic of Abiraterone : Concentration Observed Just Before Treatment Administration During Repeated Dosing at Steady State (Ctrough ss)(Pre abiraterone dose on Day 1 of Cycle 1)
- Phase 2: Percentage of Participants With Objective Response(Baseline, every 12 weeks there after until disease progression (maximum duration: 603 days))
- Phase 2: Overall Survival(From baseline up to death or study cut-off (maximum duration: 603 days))
- Phase 2: Pharmacokinetic of Cabazitaxel : Total Plasma Clearance (CL)(5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1)
- Phase 2: Pharmacokinetic of Cabazitaxel : Area Under the Plasma Concentration Versus Time Curve (AUC)(5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1)
- Phase 2: Pharmacokinetic of Cabazitaxel : Volume of Distribution at Steady State (Vss)(5 minutes before cabazitaxel infusion; at end of cabazitaxel infusion; 0.25 hours post-cabazitaxel infusion; any time between 1 to 4 hours, between 6 to 24 hours, between 48 to 96 hours post cabazitaxel infusion on Day 1-Cycle 1)
- Phase 2: Pharmacokinetic of Abiraterone : Maximum Plasma Concentration Observed (Cmax)(0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1)
- Phase 2: Pharmacokinetic of Abiraterone : First Time to Reach Cmax (Tmax)(0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1)
- Phase 2: Pharmacokinetic of Abiraterone : Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC 0-24)(0 hour (before abiraterone administration); 1, 2, 4, 6, 8, 12, 24 hours post abiraterone administration on Day 1-Cycle 1)