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 Capecitabine (Xeloda) 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 the Combination of Pertuzumab and Capecitabine
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 capecitabine (Xeloda) 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
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 palmar plantar syndrome Grade 2 or worse, or any unresolved residual chemotherapy effects
- •Prior HER2-active agents, continuous intravenous (IV) 5-fluorouracil, capecitabine, or other fluoropyrimidine
- •Any investigational agent within 28 days of study start
- •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 + Capecitabine 1000 mg/m^2 (Level 2)
Participants will receive a single 1000-mg/m^2 dose of oral (PO) capecitabine on Day -7 for pretreatment assessment. Capecitabine will then be administered on Days 1 to 14 of each 3-week cycle at a dose of 1000 mg/m^2 twice daily, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 1050-mg IV infusion. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.
干预措施: Capecitabine (Drug)
RhuMab 2C4 + Capecitabine 1000 mg/m^2 (Level 2)
Participants will receive a single 1000-mg/m^2 dose of oral (PO) capecitabine on Day -7 for pretreatment assessment. Capecitabine will then be administered on Days 1 to 14 of each 3-week cycle at a dose of 1000 mg/m^2 twice daily, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 1050-mg IV infusion. 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 + Capecitabine 1250 mg/m^2 (Level 3)
Participants will receive a single 1250-mg/m^2 dose of PO capecitabine on Day -7 for pretreatment assessment. Capecitabine will then be administered on Days 1 to 14 of each 3-week cycle at a dose of 1250 mg/m^2 twice daily, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 1050-mg IV infusion. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.
干预措施: Capecitabine (Drug)
RhuMab 2C4 + Capecitabine 1250 mg/m^2 (Level 3)
Participants will receive a single 1250-mg/m^2 dose of PO capecitabine on Day -7 for pretreatment assessment. Capecitabine will then be administered on Days 1 to 14 of each 3-week cycle at a dose of 1250 mg/m^2 twice daily, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 1050-mg IV infusion. 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 + Capecitabine 825 mg/m^2 (Level 1)
Participants will receive a single 825-mg/m^2 dose of PO capecitabine on Day -7 for pretreatment assessment. Capecitabine will then be administered on Days 1 to 14 of each 3-week cycle at a dose of 825 mg/m^2 twice daily, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 1050-mg IV infusion. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.
干预措施: Capecitabine (Drug)
RhuMab 2C4 + Capecitabine 825 mg/m^2 (Level 1)
Participants will receive a single 825-mg/m^2 dose of PO capecitabine on Day -7 for pretreatment assessment. Capecitabine will then be administered on Days 1 to 14 of each 3-week cycle at a dose of 825 mg/m^2 twice daily, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 1050-mg IV infusion. 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 the Combination of Pertuzumab and Capecitabine
时间窗: Cycle 1 (3 Weeks)
MTD was defined as the highest tolerated dose combination of capecitabine (825 mg, 1000 mg or 1250 mg) and pertuzumab, without causing Dose Limiting Toxicities (DLTs). DLTs were defined as follows: 1) Any non-hematological toxicity greater than or equal to (≥) 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 \> 7 days; 3) Febrile neutropenia; 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion; 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. Participants who withdrew from the study without completing the first treatment cycle for reasons other than DLT were not considered evaluable for DLT. MTD was measured in mg/m\^2.
次要结局
- Time to Maximum Plasma Concentration (Tmax) of Pertuzumab(Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22)
- Plasma Half-Life (t1/2) of Pertuzumab(Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and Predose on Days 8, 15 and 22)
- Maximum Plasma Concentration (Cmax) of Pertuzumab(Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22)
- Percentage of Participants With DLTs(Cycle 1 (3 Weeks))
- Area Under the Concentration Curve From Time Zero to Last Measurement (AUC 0-last) of Pertuzumab(Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22)
- AUC From Time Zero to Infinity (AUC 0-infinity) of Pertuzumab(Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22)
- Apparent Volume of Distribution of Pertuzumab(Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22)
- Apparent Total Clearance of Pertuzumab(Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22)
- Plasma Half-Life of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab(Day -7: Predose, 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours postdose; Cycle 1 Day 1: Predose, 0 and 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours Postdose)
- Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab(Day -7: Predose, 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours postdose; Cycle 1 Day 1: Predose, 0 and 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours Postdose)
- Time to Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab(Day -7: Predose, 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours postdose; Cycle 1 Day 1: Predose, 0 and 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours Postdose)