A Phase 1b Dose Escalation, Open-label Study Of CP-751,871 In Combination With Docetaxel In Advanced Non-hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 1
研究概览
简要总结
This clinical trial is designed to determine the safety, tolerability, pharmacokinetics and pharmacodynamic effects of escalating doses of CP 751,871 given in combination with docetaxel in patients with non-hematologic malignancies for whom docetaxel is a reasonable treatment option.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •Age greater than 18 years
- •Documented advanced-stage non-hematologic malignancy for whom docetaxel monotherapy is a reasonable treatment option
- •Eastern Cooperative Oncology Group [ECOG] performance status 0-1
排除标准
- •Significant active cardiac disease
- •Chemotherapy, biological or investigational agents within 4 weeks prior to dosing
- •Inadequate bone marrow, renal, cardiac or liver function
研究组 & 干预措施
CP-751,871 combined with docetaxel
干预措施: CP-751,871 (Drug)
CP-751,871 combined with docetaxel
干预措施: Docetaxel (Drug)
结局指标
主要结局
Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 1
时间窗: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Maximum Observed Plasma Concentration (Cmax) divided by dose
Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 1
时间窗: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Area under the plasma concentration versus time curve (AUC) from time zero to 25 hours post dose, the nominal time of the last sample (24 hours after end of infusion)
Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 4
时间窗: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Area under the plasma concentration versus time curve (AUC) from time zero to 25 hours post dose, the nominal time of the last sample (24 hours after end of infusion)
Maximum Tolerated Dose (MTD)
时间窗: Cycle 1 Day 1 through Cycle 1 Day 21
Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 4
时间窗: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Maximum Observed Plasma Concentration (Cmax) divided by dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 4
时间窗: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Recommended Phase 2 Dose (RP2D)
时间窗: Cycle 1 Day 1 through Cycle 1 Day 21
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Docetaxel in Cycle 1
时间窗: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Docetaxel in Cycle 4
时间窗: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 1
时间窗: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) divided by dose
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 4
时间窗: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) divided by dose
Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 1
时间窗: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 4
时间窗: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 1
时间窗: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
次要结局
- Number of Participants With Objective Response (OR)(Baseline, every 2 months (approximately 7-10 days prior to the start of the next dose) up to Cycle 17 (1 cycle = 21 days))
- Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4(30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22))
- Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1(30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22))
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 1(30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22))
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 4(30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22))
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1(30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22))
- Circulating Tumor Cells (CTCs), CTCs Expressing Insulin-like Growth Factor 1 Receptor (IGF-1R), and Circulating Endothelial Cells (CECs)(Predose on Day 1 and on Day 8 of each cycle, and End of Study (28 days after the last CP-751,871 infusion))
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1(30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22))
- Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 1(30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22))
- Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 4(30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22))
- Apparent Volume of Distribution (Vz/F) of CP-751,871 in Cycle 1(30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22))
- Time of Last Quantifiable Time Point (Tlast) of CP-751,871 in Cycle 1 and Cycle 4(Cycle 1 and 4: prior to CP-751,871 infusion, at 1 hour post CP-751,871 infusion, and at 1, 3, 7 days post end of docetaxel infusion)
- Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871(30 minutes predose at each cycle, End of Study (28 days after the last CP-751,871 infusion), and 150 days after the last CP-751,871 infusion)
- Systemic Clearance (CL) of CP-751,871 in Cycle 1(30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22))
- Systemic Clearance (CL) of CP-751,871 in Cycle 4(30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22))
- Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 4(30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22))
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4(30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22))
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4(30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22))
- Time to Tumor Progression (TTP)(Baseline, every 2 months (approximately 7-10 days prior to the start of the next dose) up to Cycle 17 (1 cycle = 21 days))
- Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1(30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22))
- Volume of Distribution (Vz) of CP-751,871 in Cycle 1(30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22))
- Apparent Volume of Distribution (Vz/F) of CP-751,871 in Cycle 4(30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22))
- Volume of Distribution (Vz) of CP-751,871 in Cycle 4(30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22))
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 1(30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22))
- Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4(Cycle 1: 30 minutes prior to the Cycle 2 CP-751,871 infusion (this is Day 22 for Cycle 1); Cycle 4: 30 minutes prior to the Cycle 5 CP-751,871 infusion (this is Day 22 for Cycle 4))
- Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 1(30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22))
- Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 4(30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22))
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4(30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22))
- Observed Accumulation Ratio (Rac) of CP-751,871(30 minutes prior to CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of CP-751,871 infusion; and 30 minutes prior to the next cycle CP-751,871 infusion (Day 22) in Cycle 1 and Cycle 4)