A STUDY OF NERATINIB PLUS CAPECITABINE VERSUS LAPATINIB PLUS CAPECITABINE IN PATIENTS WITH HER2+ METASTATIC BREAST CANCER WHO HAVE RECEIVED TWO OR MORE PRIOR HER2-DIRECTED REGIMENS IN THE METASTATIC SETTING (NALA)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 621
- 试验地点
- 236
- 主要终点
- Centrally Assessed Progression Free Survival
研究概览
简要总结
This is a randomized, multi-center, multinational, open-label, active-controlled, parallel design study of the combination of neratinib plus capecitabine versus the combination of lapatinib plus capecitabine in HER2+ MBC patients who have received two or more prior HER2 directed regimens in the metastatic setting.
详细描述
This is a randomized, multi-center, multinational, open-label, active-controlled, parallel design study of the combination of neratinib plus capecitabine versus the combination of lapatinib plus capecitabine in HER2+ MBC patients who have received two or more prior HER2 directed regimens in the metastatic setting. Patients will be randomized in a 1:1 ratio to one of the following treatment arms:
- Arm A: neratinib (240 mg once daily) + capecitabine (1500 mg/m^2 daily, 750 mg/m^2 twice daily [BID])
- Arm B: lapatinib (1250 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID)
Patients will receive either neratinib plus capecitabine combination or lapatinib plus capecitabine combination until the occurrence of death, disease progression, unacceptable toxicity, or other specified withdrawal criterion.
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
- 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
- •Aged ≥18 years at signing of informed consent.
- •Histologically confirmed MBC, current stage IV.
- •Documented HER2 overexpression or gene-amplified tumor immunohistochemistry 3+ or 2+, with confirmatory fluorescence in situ hybridization (FISH) +.
- •Prior treatment with at least two (2) HER2-directed regimens for metastatic breast cancer.
排除标准
- •Received previous therapy with capecitabine, neratinib, lapatinib, or any other HER2 directed tyrosine kinase inhibitor.
- •Note: There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.
研究组 & 干预措施
neratinib plus capecitabine
neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
干预措施: neratinib (Drug)
neratinib plus capecitabine
neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
干预措施: capecitabine (Drug)
lapatinib plus capecitabine
lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
干预措施: capecitabine (Drug)
lapatinib plus capecitabine
lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.
干预措施: lapatinib (Drug)
结局指标
主要结局
Centrally Assessed Progression Free Survival
时间窗: From randomization date to recurrence, progression or death, assessed up to 38 months. The result is based on primary analysis data cut.
Progression Free Survival (PFS), Measured in Months, for Randomized Subjects of the Central Assessment. The time interval from the date of randomization until the first date on which recurrence, progression (per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1), or death due to any cause, is documented. For subjects without recurrence, progression or death, it is censored at the last valid tumor assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to 24 months.
Overall Survival
时间窗: From randomization date to death, assessed up to 59 months.The result is based on primary analysis data cut.
Overall survival (OS) is defined as the time from randomization to death due to any cause, censored at the last date known alive on or prior to the data cutoff employed for the analysis, whichever was earlier. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to 48 months.
次要结局
- Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events)(From first dose through last dose + 28 days, up to 41 months. The result is based on final data cut.)
- Intervention for Symptomatic Metastatic Central Nervous System Disease(From randomization date to first intervention for symptomatic metastatic CNS disease, assessed up to 59 months.The result is based on primary analysis data cut.)
- Objective Response Rate (ORR) - Central Assessment (ITT Population With Measurable Disease at Screening)(From randomization date to first confirmed Complete or Partial Response, whichever came earlier, up to 42 months.The result is based on primary analysis data cut.)
- Clinical Benefit Rate (CBR) - Central Assessment (ITT Population With Measurable Disease at Screening)(From randomization date to either first confirmed CR or PR or Stable Disease, whichever came earlier, up to 42 months.The result is based on primary analysis data cut.)
- Duration of Response (DOR) - Central Assessment (Population That Had a Response With Measurable Disease at Screening)(From start date of response after randomization to first PD, up to 33 months.The result is based on primary analysis data cut.)