Phase 1 Study of Ipilimumab (BMS-734016) in Combination With Paclitaxel and Carboplatin in Japanese Patients With Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Number of Participants Experiencing a Dose-limiting Toxicity (DLT)
研究概览
简要总结
The primary purpose of this study was to establish the recommended dose of ipilimumab administered in combination with paclitaxel and carboplatin in Japanese patients with nonsmall-cell lung cancer.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically documented nonsmall-cell lung cancer (NSCLC) presenting as stage IIIB disease without indications for definitive radiotherapy, stage IV disease, or recurrent disease following radiation therapy or surgical resection
- •No prior chemotherapy, hormonal therapy, immunotherapy, or targeted-therapy-containing regimens for the treatment of NSCLC
- •Life expectancy of at least 3 months
- •Eastern Cooperative Oncology Group performance score of 0-1
- •Adequate bone marrow function
- •Hemoglobin ≥9.0 g/dL
- •Absolute neutrophil count ≥1,500/mm^3
- •Platelet count ≥100,000/mm^3
- •Adequate liver function
- •Total bilirubin level ≤2.0*the upper limit of normal (ULN)
- •Asparate aminotransferase level ≤2.5*ULN
- •Alanine aminotransferase level ≤2.5*ULN
- •Adequate renal function
- •Calculated creatinine clearance based on Cockcroft and Gault formula ≥50 mL/min.
排除标准
- •Symptomatic central nervous system (CNS) metastasis or active CNS metastasis requiring medication
- •Malignant body cavity fluid (eg, pleural effusion, cardiac effusion, ascites) that recurred despite appropriate supportive care
- •Prior radiation of ≥30% of major bone-marrow containing areas (pelvis, lumbar spine)
- •Documented history of severe autoimmune or immune-mediated symptomatic disease that required prolonged (longer than 2 months) systemic immunosuppressant treatment
- •Documented history of motor neuropathy considered of autoimmune origin (eg, Guillain Barré syndrome)
- •Any concurrent malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, carcinoma of the mucous membrane of the gastrointestinal tract, or superficial bladder cancer treated with systemic therapy
- •≥Grade 2 diarrhea
- •History of or concurrent disease of gastrointestinal tract perforations
- •≥Grade 2 peripheral neuropathy (motor or sensory)
- •Uncontrolled intercurrent illness including infection requiring systemic therapy, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled angina pectoris, uncontrolled peptic ulcer, and cardiac arrhythmia requiring medication
- •Positive finding for human immunodeficiency virus antibody, hepatitis B surface antigen, or hepatitis C virus antibody.
研究组 & 干预措施
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m^2 , administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
干预措施: Ipilimumab, 3 mg (Drug)
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m^2 , administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
干预措施: Paclitaxel (Drug)
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m^2 , administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
干预措施: Carboplatin (Drug)
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m^2 , administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
干预措施: Ipilimumab, 10 mg (Drug)
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m^2 , administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
干预措施: Paclitaxel (Drug)
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m^2 , administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
干预措施: Carboplatin (Drug)
结局指标
主要结局
Number of Participants Experiencing a Dose-limiting Toxicity (DLT)
时间窗: Day 1 of Cycles 1 and 2 From Day 1 of Cycle 3 to Day 21 of Cycle 4
A DLT was defined as study drug-related adverse event occurring during the first 2 cycles after ipilimumab administration in the induction phase and was any of the following: Grade 4 absolute neutrophil count (ANC) decreased (\<500 cells/ mm\^3) for 7 or more consecutive days; febrile Neutropenia (body temperature ≥38.5° C with ANC \<1000 /mm\^3) lasting \>3 days; Grade 4 platelet count decreased (\<25,000 cells/mm\^3) or Grade 3 platelet count decreased requiring a platelet transfusion; Grade 3 or greater nausea, vomiting, diarrhea, despite the use of adequate/maximal medical intervention; Grade 3 or greater aspartate transaminase/alanine transaminase level and rash that has not resolved to Grade 2 or lower within 2 weeks after onset; or any Grade 3 or greater nonhematologic toxicity (except Grade 3 fatigue, Grade 3 asthenia, Grade 3 transient arthralgia/myalgia, or Grade 3 transient abnormal electrolyte levels).
次要结局
- Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs Leading to Discontinuation(Continuously from Day 1 to Week 24 and every12 weeks thereafter during maintenance until discontinuation of drug)
- Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease(Day 1 of Cycle 3, Day 1 of Cycle 5, and Day 22 of Cycle 6)
- Maximum Serum Concentration (Cmax) of Ipilimumab(During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab)
- Trough Observed Serum Concentration (Cmin) of Ipilimumab(During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab)
- Time of Maximum Observed Serum Concentration (Tmax)(During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab)
- Serum Half-life (T-HALF) of Ipilimumab(During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab)
- Area Under the Concentration Curve From Time 0 to Day 21 (in 1 Interval Dosing) (AUC[0-21d]) for Ipilimumab(During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab)