A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase III Study of Lapatinib (GW572016) in Combination With Paclitaxel Versus Paclitaxel Plus Placebo in Subjects With ErbB2 Amplified Metastatic Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 444
- 试验地点
- 1
- 主要终点
- Overall Survival (OS) at 53 Months
研究概览
简要总结
This was a randomized, double-blind, placebo-controlled, multicenter, Phase III study to evaluate and compare the efficacy and safety of Lapatinib + Paclitaxel versus Placebo + Paclitaxel in men and women with ErbB2 amplified metastatic (Stage IV) breast cancer who had not received prior therapy for metastatic disease.
详细描述
Subjects were randomized to receive either Lapatinib (1500 mg once daily) + Paclitaxel (80 mg/m2 IV weekly for 3 weeks every 4 weeks) or Placebo (once daily) + Paclitaxel (80 mg/m2 IV weekly for 3 weeks every 4 weeks).
Subjects who progressed while on study and were on the placebo+paclitaxel arm were permitted to enter an extension phase of open label monotherapy therapy with lapatinib or open label combination therapy with lapatinib+paclitaxel and followed for response, progression and survival.
Based on the positive results in the primary analysis, Protocol Amendment 02 (dated 09 May 2011) discontinued further entry into the lapatinib monotherapy extension phase, and ongoing subjects taking placebo were permitted to replace it with open label lapatinib therapy (with or without continued paclitaxel therapy).
Following the primary Overall Survival (OS) analysis and subsequent implementation of Protocol Amendment 03, subjects who were still receiving active treatment entered the Long-term follow-up (LTFU) phase of the study. Reporting requirements in the LTFU phase were limited to Adverse events of special interest (AESI), Serious adverse events (SAEs) and pregnancy, and the subjects continued to receive treatment until the occurrence of unacceptable toxicity or disease progression (as determined by the investigator) or permanent withdrawal from treatment for any reason. Subjects who were no longer receiving active treatment were withdrawn from the study.
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
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Pregnant or lactating females at anytime during the study
- •Subjects with only non-measurable metastatic sites of disease per RECIST, (e.g. bone metastases, pleural effusion, or ascites, etc. (Refer to Section 5.3 Efficacy for list sites considered to be non-measurable disease.);
- •Received prior chemotherapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for metastatic disease.
- •Prior therapy with an ErbB1 and/or ErbB2 inhibitor, other than trastuzumab in the adjuvant setting. If trastuzumab was administered in the adjuvant setting, then > 12 months must have elapsed since completion of trastuzumab therapy;
- •Planned concurrent anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy) while taking investigational treatment;
- •Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
- •Peripheral neuropathy of Grade 2 or greater;
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded;
- •History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, are eligible;
- •Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject's safety;
- •Uncontrolled infection;
- •Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
- •Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure;
- •Known history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis;
- •Concurrent treatment with prohibited medications, including herbal remedies and Chinese traditional medicines;
- •Concurrent treatment with an investigational agent or participation in another clinical trial involving investigational agents;
- •Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of investigational treatment;
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to paclitaxel or lapatinib or their excipients.
研究组 & 干预措施
Paclitaxel and Lapatinib (Blinded)
Paclitaxel and Lapatinib (Blinded)
干预措施: Lapatinib (GW572016) oral tablets (Drug)
Paclitaxel and Lapatinib (Blinded)
Paclitaxel and Lapatinib (Blinded)
干预措施: Paclitaxel infusion (Drug)
Paclitaxel and Placebo (Blinded)
Paclitaxel and Placebo (Blinded)
干预措施: Paclitaxel infusion (Drug)
Paclitaxel and Placebo (Blinded)
Paclitaxel and Placebo (Blinded)
干预措施: Placebo (Drug)
Open Label - Monotherapy (Extension Phase)
Open Label - Monotherapy (Lapatinib)
干预措施: Lapatinib (GW572016) oral tablets (Drug)
Open Label - Combination Therapy (Extension Phase)
Open Label - Combination Therapy (Lapatinib and Paclitaxel)
干预措施: Lapatinib (GW572016) oral tablets (Drug)
Open Label - Combination Therapy (Extension Phase)
Open Label - Combination Therapy (Lapatinib and Paclitaxel)
干预措施: Paclitaxel infusion (Drug)
结局指标
主要结局
Overall Survival (OS) at 53 Months
时间窗: From date of randomization until date of death from any cause, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010)
Overall Survival (OS) was defined as the interval of time (in months) between the date of randomization and the date of death due to any cause.
次要结局
- Overall Response Rate (ORR) by Investigator Assessment(From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 190 months (Final analysis cut-off date = 23-Nov-2021))
- Duration of Response (DOR)(From date of confirmed CR or PR until date of progression or date of death from any cause, whichever comes first, assessed up to 190 months (Final analysis cut-off date = 23-Nov-2021))
- Number of Participants With a CR or PR at Weeks 8, 12, 16, 24, 32, 40, 48, 56, 64, and 72(Weeks 8, 12, 16, 24, 32, 40, 48, 56, 64, and 72)
- Number of Tumors Evaluable for PIK3CA Mutations(Baseline)
- Number of Participants With Tumors Evaluable for PTEN(Baseline)
- Predictive Effect of PIK3CA Mutations Status on Overall Response Rate (ORR)(From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010))
- Overall Survival (OS) at 190 Months(From date of randomization until date of death from any cause, assessed up to 190 months (Final OS analysis cut-off date = 23-Nov-2021))
- Progression-free Survival (PFS) by Investigator Assessment(From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to 190 months (Final analysis cut-off date = 23-Nov-2021))
- Clinical Benefit Rate (CBR)(From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary analysis cut-off date = 18-Jun-2010))
- Predictive Effect of PTEN Low on Overall Response Rate (ORR)(From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010))
- Predictive Effect of PIK3CA Mutations Status on Clinical Benefit Rate (CBR)(From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010))
- Predictive Effect of PTEN Low on Clinical Benefit Rate (CBR)(From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010))