A Phase 1b Dose Escalation/Phase 2 Randomized, Non-Comparative, Multiple Center, Open Label Study Of CP 751,871 In Combination With Paclitaxel And Carboplatin And Of Paclitaxel And Carboplatin Alone As First Line Treatment For Advanced Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 282
- 试验地点
- 1
- 主要终点
- Objective Response Rate in Non-Adenocarcinoma Participants: Phase 2
研究概览
简要总结
Phase 1b Dose Excalation/Expansion: Identify and characterize safety and tolerability of recommended phase 2 dose of CP-751,871 when administered with paclitaxel and carboplatin Phase 1b Erlotinib Extension: To characterize the safety and tolerability of CP751,871 when administered with paclitaxel, carboplatin and erlotinib.
Phase 2: To test the efficacy of CP-751,871 combined with paclitaxel and carboplatin in the treatment of advanced non-small cell lung cancer
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
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of advanced/metastatic lung cancer
排除标准
- •Previous treatment with chemotherapy
- •Uncontrolled diabetes
- •History/active cardiovascular disease
研究组 & 干预措施
Phase 2 (Arms A & B)
CP-751,871 + paclitaxel + carboplatin
干预措施: CP-751,871 (Drug)
Phase 2 (Arms A & B)
CP-751,871 + paclitaxel + carboplatin
干预措施: paclitaxel (Drug)
Phase 2 (Arms A & B)
CP-751,871 + paclitaxel + carboplatin
干预措施: carboplatin (Drug)
Phase 1b
- Phase 1b Dose Escalation /Expansion: CP-751,871 + paclitaxel + carboplatin
- Phase 1b Erlotinib Extension: CP-751,871 + paclitaxel + carboplatin + erlotinib
干预措施: CP-751,871 (Drug)
Phase 1b
- Phase 1b Dose Escalation /Expansion: CP-751,871 + paclitaxel + carboplatin
- Phase 1b Erlotinib Extension: CP-751,871 + paclitaxel + carboplatin + erlotinib
干预措施: paclitaxel (Drug)
Phase 1b
- Phase 1b Dose Escalation /Expansion: CP-751,871 + paclitaxel + carboplatin
- Phase 1b Erlotinib Extension: CP-751,871 + paclitaxel + carboplatin + erlotinib
干预措施: carboplatin (Drug)
Phase 1b
- Phase 1b Dose Escalation /Expansion: CP-751,871 + paclitaxel + carboplatin
- Phase 1b Erlotinib Extension: CP-751,871 + paclitaxel + carboplatin + erlotinib
干预措施: erlotinib (Drug)
结局指标
主要结局
Objective Response Rate in Non-Adenocarcinoma Participants: Phase 2
时间窗: Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization
Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
Recommended Phase 2 Dose (RP2D): Phase 1b
时间窗: Start of treatment (baseline) up to the end of Cycle 1 (Day 21)
Objective Response Rate: Phase 2
时间窗: Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization
Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
Maximum Tolerated Dose (MTD)of CP-751,871 in Combination With Paclitaxel and Carboplatin: Phase 1b
时间窗: Start of treatment (baseline) up to the end of Cycle 1 (Day 21)
The maximum tolerated dose of CP-751,871 in combination with paclitaxel and carboplatin is the highest dose level below the Maximum Administered Dose (the dose level at which 2 or more out of 3 to 6 patients experience a Dose Limiting Toxicity at a dose level in Cycle 1) at which none or one out of 6 patients experience a Cycle 1 Dose Limiting Toxicity.
次要结局
- Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 1b(Day 1 pre-infusion of each cycle up to Cycle 17 (each cycle was 21 day), 150 days after the last CP-751,871 infusion, and last follow up visit (one year post last study dose))
- Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b(Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1))
- Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 1 in Phase 1b(Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1))
- Number of Circulating Endothelial Cells (CECs): Phase 1b(Day 1 pre-dose and Days 15 to 21 of Cycle 4)
- Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b(Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4))
- Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 for Cycle 1 in Phase 1b(Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1))
- Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 4 in Phase 1b(Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4))
- Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b(Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4))
- Objective Response Rate: Phase 1b(Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization)
- Number of Circulating Tumor-Related Cells (CTCs) and CTC Insulin-Like Growth Factor 1 Receptor (IGF-IR) Expression: Phase 1b(Day 1 pre-dose and Days 15 to 21 of Cycle 4)
- CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 2(Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4).)
- CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b(Cycle 2 pre-infusion (which is the end of Cycle 1))
- Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b(Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1). Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4).)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b(Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1))
- Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b(Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1))
- Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 1 in Phase 1b(Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1))
- Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 4 in Phase 1b(Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4))
- CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b(Cycle 5 pre-infusion (which is the end of Cycle 4))
- Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b(Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is then end of Cycle 4))
- Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 2(Day 1 pre-infusion of each Cycle (each cycle was 21 day) up to Cycle 17 and 150 days after the last CP-751,871 infusion)
- M.D. Anderson Symptom Assessment Inventory (MDASI) in Phase 2(Day 1 pre-dose of Cycle 1, weekly for Cycle 1 and 2, monthly prior to each subsequent cycle (Cycle 3 up to Cycle 17, each cycle was 21 day), and follow up (one year post last study dose))
- Apparent Volume of CP-751,871 Distribution (Vd) for Cycle 4 in Phase 2(Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4))
- Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 4 in Phase 2(Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4).)
- Progression-Free Survival (PFS): Phase 2(Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization)
- The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC-QLQ-C30/-LC13) in Phase 2(Day 1 pre-dose of Cycle 1, monthly prior to each cycle (up to 17 cycles, each cycle was 21 day), and follow up (one year post last study dose))
- Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 2(Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4).)
- Clearance (CL) of CP-751,871 for Cycle 4 in Phase 2(Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4).)
- Time to Progression (TTP) in Phase 2(Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization)
- Duration of Response (DR) in Phase 2(Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization)