A Phase Ib, Open-Label, Multicenter Study of the Safety and Pharmacokinetics of the Combination of RhuMab 2C4 (Omnitarg), a Recombinant Humanized Antibody to HER2, and Docetaxel (Taxotere) in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 主要终点
- Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab
研究概览
简要总结
This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of rhuMab 2C4 (Perjeta) and docetaxel (Taxotere) in participants with advanced solid tumors that have progressed during or after standard therapy, or for which no standard therapy is available. Participants will be enrolled and evaluated for dose-limiting toxicities (DLTs) in escalating-dose cohorts in order to determine the maximum tolerated dose (MTD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Adults at least 18 years of age
- •Easter Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy at least 12 weeks
- •Locally advanced or metastatic solid tumor with at least 1 measurable lesion, which has progressed during/after standard therapy
- •Human epidermal growth factor receptor 2 (HER2)-negative among participants with breast cancer
- •Negative pregnancy test or use of an adequate contraceptive method among women of childbearing potential
- •Adequate hematologic, hepatic, and renal function
- •Signed informed consent, histologically or cytologicall confirmed advanced solid tumor, adequate cardiac function as documented by LVEF >50% by ECHO or MUGA
排除标准
- •Clinical evidence of central nervous system (CNS) metastases
- •Prior chemotherapy, radiotherapy, or immunotherapy within 4 weeks, or hormone therapy within 2 weeks of study Day 1
- •History of neuropathy Grade 2 or worse, or any unresolved residual chemotherapy effects
- •Prior HER2-active agents or docetaxel
- •Any investigational agent within 28 days of study drug
- •Prior cumulative doxorubicin dose greater than (>) 360 mg/m^2 or equivalent
- •Significant cardiovascular disease
- •Active/uncontrolled concurrent illness or infection-
- •Major surgery or trauma within 4 weeks of study Day 1
研究组 & 干预措施
RhuMab 2C4 + Docetaxel 100 mg/m^2 (Level 3)
Docetaxel will be administered via intravenous (IV) infusion on Day 1 of each 3-week cycle at a dose of 100 mg/m^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.
干预措施: Docetaxel (Drug)
RhuMab 2C4 + Docetaxel 100 mg/m^2 (Level 3)
Docetaxel will be administered via intravenous (IV) infusion on Day 1 of each 3-week cycle at a dose of 100 mg/m^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.
干预措施: RhuMab 2C4 (Drug)
RhuMab 2C4 + Docetaxel 60 mg/m^2 (Level 1)
Docetaxel will be administered via IV infusion on Day 1 of each 3-week cycle at a dose of 60 mg/m^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.
干预措施: Docetaxel (Drug)
RhuMab 2C4 + Docetaxel 60 mg/m^2 (Level 1)
Docetaxel will be administered via IV infusion on Day 1 of each 3-week cycle at a dose of 60 mg/m^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.
干预措施: RhuMab 2C4 (Drug)
RhuMab 2C4 + Docetaxel 75 mg/m^2 (Level 2)
Docetaxel will be administered via IV infusion on Day 1 of each 3-week cycle at a dose of 75 mg/m^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.
干预措施: Docetaxel (Drug)
RhuMab 2C4 + Docetaxel 75 mg/m^2 (Level 2)
Docetaxel will be administered via IV infusion on Day 1 of each 3-week cycle at a dose of 75 mg/m^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.
干预措施: RhuMab 2C4 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab
时间窗: Cycle 1 Up to Day 15
A prior dose level was defined as an MTD if at a certain dose level, there were greater than or equal to (≥) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs). If there were no DLTs or DLTs were seen in less than (\<) 2 participants in the highest dose level, that was considered as MTD. Participants received escalating doses of docetaxel and pertuzumab until DLTs were observed. DLTs were defined as any of the following: 1) Any non-hematological toxicity ≥ Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (\>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds.
次要结局
- Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel(Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22)
- Mean Residence Time (MRT) of Pertuzumab(Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22)
- Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint(Baseline, Weeks 7(Cycle 2), 13 (Cycle 4) and Final Visit Up to Week 22)
- Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel(Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22)
- AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel(Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22)
- Clearance (Cl) of Pertuzimab in Combination With Docetaxel(Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22)
- Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel(Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22)
- Vss for Docetaxel Alone and in Combination With Pertuzumab(Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose)
- CL for Docetaxel Alone and in Combination With Pertuzumab(Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose)
- Number of Participants With DLTs(From Baseline until 4 weeks after the end of treatment)
- Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel(Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22)
- Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria(Weeks 7 (Cycle 2),13 (Cycle 4) and Final Visit Up to 22 weeks)
- AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab(Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose)
- t1/2 for Docetaxel Alone and in Combination With Pertuzumab(Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose)
- Tmax for Docetaxel Alone and in Combination With Pertuzumab(Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose)
- Cmax for Docetaxel Alone and in Combination With Pertuzumab(Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose)