A Randomized, Multicenter, Double-Blind, Placebo-Controlled, 2-Arm, Phase III Study of Oral GW572016 in Combination With Paclitaxel in Subjects Previously Untreated or Advanced or Metastatic Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 580
- 试验地点
- 1
- 主要终点
- Time to Progression as Evaluated by the Investigator
研究概览
简要总结
The purpose of this study is to determine the efficacy and safety of an oral dual tyrosine kinase inhibitor (GW572016) in combination with paclitaxel compared to paclitaxel alone in first line advanced or metastatic breast 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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1
Lapatinib 1500 mg, once daily and Paclitaxel 175 mg/m Intravenously over 3 hours ever 3 weeks
干预措施: Paclitaxel (Drug)
Arm 1
Lapatinib 1500 mg, once daily and Paclitaxel 175 mg/m Intravenously over 3 hours ever 3 weeks
干预措施: GW572016 (Lapatinib) (Drug)
Arm 2
Paclitaxel 175 mg/m Intravenously over 3 hours ever 3 weeks and Placebo
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Time to Progression as Evaluated by the Investigator
时间窗: Randomization until the date of disease progression or death (average of 26 weeks)
Time to progression (TTP) is defined as the interval between the date of randomization and the earliest date of progression of disease (PD) or death due to breast cancer. The investigator assessed PD based on radiological PD (imaging data) and clinical symptomatic progress (Response Evaluation Criteria in Solid Tumors \[RECIST\] Criteria: target lesion (TL), at least a 20% increase in the sum of largest diameter (LD) of TLs or the appearance of one or more new lesions; non-TL (NTL), the appearance of one or more new lesions and/or unequivocal progression of existing NTLs). TTP was assessed in participants who died due to breast cancer or progressed, as assessed by the investigator, as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored participants (those without a documented date of disease progression/death due to breast cancer), the date of the last radiographic assessment was used.
Time to Progression as Evaluated by the Independent Review Committee (IRC)
时间窗: Randomization until the date of disease progression or death (average of 26 weeks)
Time to progression is defined as the interval between the date of randomization and the earliest date of progression of disease (PD) or death due to breast cancer. The IRC assessed PD based on radiological PD (imaging data) and clinical symptomatic progress (Response Evaluation Criteria in Solid Tumors \[RECIST\] Criteria: target lesion (TL), at least a 20% increase in the sum of largest diameter (LD) of TLs or the appearance of one or more new lesions; non-TL (NTL), the appearance of one or more new lesions and/or unequivocal progression of existing NTLs). TTP was assessed in participants who died due to breast cancer or progressed, as assessed by the independent reviewer, as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored participants (those without a documented date of disease progression/death due to breast cancer), the date of the last radiographic assessment was used.
次要结局
- Duration of Response (DOR)(From the time of the first documented complete or partial response until the first documented evidence of progression or death (average of 26 weeks))
- Progression-Free Survival (PFS)(Randomization until the date of disease progression or death (average of 26 weeks))
- Number of Participants Who Progressed or Died at or Prior to 6 Months, as a Measure of Six Months Progression-free Survival (PFS)(Randomization until the date of disease progression or death (average of 26 weeks))
- Overall Survival(Randomization until the date of death due to any cause (average of 24 months))
- Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Scores(Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal)
- Number of Participants With Tumor Response as Evaluated by the Investigator(Randomization until the date of disease progression or death (average of 26 weeks))
- Number of Participants With Tumor Response as Evaluated by the Independent Review Committee(Randomization until the date of disease progression or death (average of 26 weeks))
- Percentage of Participants With Clinical Benefit (CB) as Assessed by the Investigator(Randomization until the date of disease progression or death (average of 26 weeks))
- Number of Participants With a Response of CR or PR by the Indicated Study Week(Weeks 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, and 72)
- Serum ErbB2 Concentration(Screening (Day-1) and Withdrawal (up to Study Week 129))
- Number of Participants With the Indicated Adverse Events (AEs) With a Maximum Toxicity Grade of 3 or 4(Baseline (Day 1) until 30 days after the last dose of randomized therapy (average of 26 weeks))
- Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores(Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal)
- Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores(Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal)
- Number of Participants With the Indicated ErbB2 Status at Baseline(Baseline)
- ErbB2 Ratio(Baseline)
- Number of Participants With the Indicated Immunohistochemistry (IHC) Results at Screening(Screening (Day -1))
- Number of Participants With the Indicated ErbB2 Fluorescence in Situ Hybridization (FISH) Results(Baseline)
- Serum ErbB1 Concentration(Screening (Day-1) and Withdrawal (up to Study Week 129))