A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Study Comparing GW572016 and Letrozole Versus Letrozole in Subjects With Estrogen/Progesterone Receptor- Positive Advanced or Metastatic Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,286
- 试验地点
- 1
- 主要终点
- Number of Participants With Progression Free Survival (PFS) in the Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced or Metastatic Breast Cancer as Assessed by the Investigator
研究概览
简要总结
This study evaluated and compared the efficacy and tolerability of lapatinib and letrozole, with letrozole and placebo in post-menopausal women with hormone receptor positive (ER positive and/or PgR positive) advanced or metastatic breast cancer, who had not received prior therapy for advanced or metastatic disease.
详细描述
Subjects were randomly assigned to receive either lapatinib (1500 mg once daily orally) with letrozole (2.5 mg once daily orally), or letrozole (2.5 mg once daily orally) with placebo (which matched with lapatinib tablet). Randomization was stratified by site of disease (i.e., soft tissue/visceral disease versus bone only disease) and time since prior adjuvant endocrine therapy (<6 months or ≥ 6 months from discontinuation of adjuvant anti-estrogen therapy (e.g. tamoxifen or raloxifene) or no prior adjuvant antiestrogen therapy). Study therapy was administered daily until disease progression (objective or symptomatic) or withdrawal from therapy (e.g., due to unacceptable toxicity, withdrawal of consent, or other reason). All subjects were to be followed for survival information until death.
On 13 Apr 2015, after the introduction of the Long Term Follow UP (LTFU) phase (per protocol amendment 07), subjects receiving study treatment with lapatinib plus letrozole, or letrozole plus placebo had continued access to this study treatment until the occurrence of one of the following criteria:
- Disease progression (as determined by the Investigator),
- Intercurrent illness that prevented further administration of study treatment
- Drug related AE which was considered by the investigator to warrant permanent discontinuation of study treatment
- The subject decided to withdraw from the study. Investigators collected AEs and/or SAEs related to study participation, until 30 days following study treatment discontinuation. Subjects who were being followed-up for OS but were not taking study medication, were withdrawn from the study.
The study was terminated on 22-Mar-2018 (last subject last visit).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
Lapatinib 1500 mg + Letrozole 2.5 mg
Lapatinib (1500 mg once daily orally) with Letrozole (2.5 mg once daily orally)
干预措施: Lapatinib (Drug)
Placebo + Letrozole 2.5 mg
Letrozole (2.5 mg once daily orally) with Placebo (which matched with Lapatinib tablet)
干预措施: Placebo (Drug)
Placebo + Letrozole 2.5 mg
Letrozole (2.5 mg once daily orally) with Placebo (which matched with Lapatinib tablet)
干预措施: Letrozole (Drug)
Lapatinib 1500 mg + Letrozole 2.5 mg
Lapatinib (1500 mg once daily orally) with Letrozole (2.5 mg once daily orally)
干预措施: Letrozole (Drug)
结局指标
主要结局
Number of Participants With Progression Free Survival (PFS) in the Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced or Metastatic Breast Cancer as Assessed by the Investigator
时间窗: From the date of randomization until the date of the first documented progression or date of death from any cause, whichever came first, assessed for up to 46 months
PFS is defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause, if sooner. The date of documented PD is defined as the date of radiological PD as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per Response Evaluation Criteria in Solid Tumors (RECIST 1.0), PD is defined as a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions.
Progression Free Survival (PFS) of Participants in the HER2-Positive Population as Assessed by the Investigator
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months
PFS is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. The date of documented disease progression is defined as the date of radiological disease progression as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per RECIST 1.0, disease progression is defined as a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions.
次要结局
- Time to Progression (TTP) for the HER2-Positive Population as Assessed by the Investigator(Up to 46 months)
- Clinical Benefit (CB) in the ITT Population as Assessed by the Investigator(Up to 46 months)
- TTP for Participants From the ITT Population as Assessed by the Investigator(Up to 46 months)
- Number of Participants With the Indicated Best Response From the Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator.(Up to 46 months)
- Overall Survival in the ITT Population(From date of randomization until date of death due to any cause, assessed up to 46 months)
- Duration of Response for the Participants With CR or PR in the ITT Population as Assessed by the Investigator(Up to 46 months)
- Number of Participants With PFS in the Intent-To-Treat (ITT) Population as Assessed by the Investigator(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months)
- PFS in Participants in the ITT Population as Assessed by the Investigator(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months)
- Overall Survival in the HER2-Positive Population(From date of randomization until date of death due to any cause, assessed up to 46 months)
- Overall Tumor Response (OR) for Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator(Up to 46 months)
- Number of Participants With Overall Tumor Response (OR) by Stratification Factors With Measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator(Up to 46 months)
- Number of Participants With the Indicated Best Response From the Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator.(Up to 46 months)
- Number of Participants With Response in Participants With Baseline Serum HER2 Extracellular Domain (ECD) Baseline Values Greater Than 15 Nanograms Per Milliliter (ng/mL) and 15 ng/mL or Lower(Up to 46 months)
- Clinical Benefit (CB) in the HER2-Positive Population as Assessed by the Investigator(Up to 46 months)
- Number of Participants With the Indicated Time to Response for CR or PR in the HER2-Positive Population as Assessed by the Investigator(Up to 46 months)
- Number of Participants With Overall Tumor Response (OR) by Stratification Factors With Measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator(Up to 46 months)
- Number of Participants With the Indicated Time to Response for CR or PR in the ITT Population as Assessed by the Investigator(Up to 46 months)
- Number of Participants Completing the Functional Assessment of Cancer Therapy-breast (FACT-B) Questionnaire at the Scheduled Visits(Day 1 (baseline) visit; Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192 visits; conclusion/withdrawal visit)
- Adjusted Mean Change From Baseline for the Trial Outcome Index (TOI) Score Using Observed Data(Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit)
- Number of Participants Classified as QOL Responders Based on the FACT-B, FACT-G, and TOI Total Scores(Up to 46 months)
- Number of HER2-Negative Participants at Baseline With and Without Seroconversion to a Status of HER2 Positive(Up to 46 months)
- Duration of Response for the Participants With CR or PR in the HER2-Positive Population as Assessed by the Investigator(Up to 46 months)
- Number of Participants With Evidence of Brain Metastases in the HER2-Positive Population(Up to 46 months)
- Overall Tumor Response (OR) for Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator(Up to 46 months)
- Number of Participants With Clinical Benefit Categorized by HER2 Fluorescence in Situ Hybridization (FISH) Status(Up to 46 months)
- Number of Participants With Evidence of Brain Metastases From the ITT Population(Up to 46 months)
- Number of Participants With Clinical Benefit Categorized by HER2 ImmunoHistoChemistry (IHC) Intensity(Up to 46 months)
- Time to Seroconversion for Participants Who Were HER2 Negative at Baseline But Became HER2 Positive(Up to 46 months)
- Adjusted Mean Change From Baseline for the FACT-B Total Score Using Observed Data(Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit)
- Adjusted Mean Change From Baseline for the Functional Assessment of Cancer Therapy-General (FACT-G) Score Using Observed Data(Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit)
- Number of Participants With the Indicated Expression of Tumor by Epidermal Growth Factor Receptor (ErbB1/HER1/EGFR) at Baseline(Baseline)