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Ribociclib 在 HR 阳性、HER2 阴性、晚期乳腺癌的绝经前和绝经后中国女性中的疗效和安全性。

2026年6月11日 更新者：Novartis Pharmaceuticals

LEE011(Ribociclib) 或安慰剂联合内分泌治疗治疗 HR 阳性、HER2 阴性、晚期乳腺癌的绝经前和绝经后中国女性的 II 期随机、双盲、安慰剂对照研究，包括药代动力学分析。

这是一项涉及绝经前和绝经后中国女性的 II 期随机、双盲、安慰剂对照研究以及 LEE011 联合来曲唑治疗中国绝经后 HR+、HER2 阴性晚期乳腺癌女性的开放标签单臂药代动力学队列.

将招募三个患者队列：PK 队列、绝经前队列和绝经后队列。

研究概览

地位

完全的

条件

干预/治疗

详细说明

The study included three cohorts of subjects: a premenopausal cohort and a postmenopausal cohort, both randomized and double-blind, and an open-label, single-arm pharmacokinetic (PK) cohort of postmenopausal women.

The premenopausal cohort assessed the efficacy and safety of treatment with a non-steroidal aromatase inhibitor (NSAI; letrozole or anastrozole) combined with goserelin and ribociclib, compared with NSAI plus goserelin and placebo. The postmenopausal cohort assessed the efficacy and safety of ribociclib plus letrozole versus placebo plus letrozole.

The study consisted of three periods: screening, treatment, and follow-up.

  1. Screening phase: The study began with a 28-day screening period during which potential participants were evaluated against inclusion and exclusion criteria before initiating treatment on Day 1.
  2. Treatment phase: Eligible participants in the premenopausal and postmenopausal cohorts were randomized in a 1:1 ratio to one of two treatment arms, while participants in the PK cohort were not randomized. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent, loss to follow-up, or study termination. Following a statistically significant progression-free survival (PFS) benefit observed at the primary analysis and implementation of Protocol Amendment 5 (dated 18-Oct-2022), participants and investigators were unblinded. Participants still receiving placebo were offered the option to cross over to ribociclib, at the investigator's discretion and with participant consent.

  3. Follow-up phase:

    • Safety follow-up: All participants were followed for safety for up to 30 days after the last dose of study treatment, except in cases of death, loss to follow-up, or withdrawal of consent.
    • Efficacy follow-up: Tumor assessments were performed at baseline and every 8 weeks (±1 week) from randomization for the first 18 months, then every 12 weeks (±1 week) until 36 months, and thereafter as clinically indicated until progression. Participants who discontinued treatment for reasons other than disease progression continued tumor assessments according to the same schedule until progression, death, withdrawal of consent, or loss to follow-up.
    • Survival follow-up: Survival status was assessed every 12 weeks (±1 week) for all participants, regardless of treatment discontinuation reason, unless consent was withdrawn.

The end of the study was defined as the earliest occurrence of one of the following: all participants had discontinued or died; a new clinical study offering ribociclib became available and all ongoing participants were eligible for transfer; or participants still benefiting from treatment could continue receiving it through an alternative setting.

研究类型

介入性

注册 (实际的)

327

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 中国
      • Beijing、中国、100036
        • Novartis Investigative Site
      • Fuzhou、中国、350001
        • Novartis Investigative Site
      • Qingdao、中国、266000
        • Novartis Investigative Site
      • Shanghai、中国、200032
        • Novartis Investigative Site
      • Shanghai、中国、200025
        • Novartis Investigative Site
      • Tianjin、中国、300480
        • Novartis Investigative Site
    • Anhui
      • Hefei、Anhui、中国、230001
        • Novartis Investigative Site
    • Beijing Municipality
      • Beijing、Beijing Municipality、中国、100044
        • Novartis Investigative Site
    • Chongqing Municipality
      • Chongqing、Chongqing Municipality、中国、404100
        • Novartis Investigative Site
    • Guangdong
      • Guangzhou、Guangdong、中国、510000
        • Novartis Investigative Site
    • Hebei
      • Shijiazhuang、Hebei、中国、050011
        • Novartis Investigative Site
    • Heilongjiang
      • Harbin、Heilongjiang、中国、150081
        • Novartis Investigative Site
    • Hunan
      • Changsha、Hunan、中国、410013
        • Novartis Investigative Site
    • Jiangsu
      • Nanjing、Jiangsu、中国、210029
        • Novartis Investigative Site
      • Suzhou、Jiangsu、中国、215004
        • Novartis Investigative Site
    • Jiangxi
      • Nanchang、Jiangxi、中国、330009
        • Novartis Investigative Site
    • Jilin
      • Changchun、Jilin、中国、130021
        • Novartis Investigative Site
    • Liaoning
      • Shengyang、Liaoning、中国、110016
        • Novartis Investigative Site
      • Shengyang、Liaoning、中国、110042
        • Novartis Investigative Site
    • Shanxi
      • Xian、Shanxi、中国、710061
        • Novartis Investigative Site
    • Sichuan
      • Chengdu、Sichuan、中国、610041
        • Novartis Investigative Site
    • Yunnan
      • Kunming、Yunnan、中国、650106
        • Novartis Investigative Site
    • Zhejiang
      • Hangzhou、Zhejiang、中国、310016
        • Novartis Investigative Site
      • Hangzhou、Zhejiang、中国、310006
        • Novartis Investigative Site

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 60年 (成人)

接受健康志愿者

不

描述

纳入标准：

  • 患者经当地实验室（基于最近分析的活组织检查）经组织学和/或细胞学证实诊断为雌激素受体 (ER) 阳性和/或孕激素受体阳性乳腺癌。
  • 患者患有 HER2 阴性乳腺癌（基于最近分析的活组织检查），定义为原位杂交试验阴性或免疫组织化学 (IHC) 状态为 0、1+ 或 2+。 如果 IHC 为 2+，则需要当地实验室检测进行阴性原位杂交（FISH、CISH 或 SISH）检测。

  • 患者必须有：

    • 可测量的疾病，即根据实体瘤反应评估标准 (RECIST) 1.1 标准至少有 1 个可测量的病灶（如果自照射以来有明显的进展迹象，则先前照射部位的病灶只能算作目标病灶). 或者
    • 如果不存在可测量的疾病，则必须存在至少 1 个主要溶解性骨病变（如果有骨病变疾病进展的书面证据，则没有可测量疾病并且只有 1 个以前接受过照射的主要溶解性骨病变的患者符合条件照射后）。
  • 患者的 ECOG 体能状态为 0 或 1。

对于绝经前队列：

  • 患者是一名成年女性，在知情同意时年龄≥ 18 岁且 < 60 岁，并且在进行任何与试验相关的活动之前并根据当地指南签署了知情同意书。
  • 在开始研究治疗之前确认血清妊娠试验阴性或患者进行了子宫切除术。
  • 患者患有晚期（不适合治愈性治疗的局部复发或转移性）乳腺癌，不适合治愈性治疗（例如

手术和/或放疗）。

  • 在随机化之前接受 NSAI（来曲唑或阿那曲唑）联合或不联合戈舍瑞林或戈舍瑞林 ≤ 28 天的晚期乳腺癌患者符合条件。 在研究期间，患者必须继续使用相同的激素药物 + 戈舍瑞林进行治疗。 这些患者在随机化之前不需要中断治疗。
  • 已接受最多 1 线晚期乳腺癌化疗且在随机分组前 28 天停止化疗的患者符合条件。

对于绝经后队列：

  • 患者是在知情同意时年满 18 岁的成年女性，并且在进行任何试验相关活动之前已根据当地指南签署知情同意书。
  • 不适合治愈性治疗的晚期（局部复发或转移性）乳腺癌女性。

排除标准：

  • 先前接受过 CDK4/6 抑制剂治疗的患者。
  • 根据研究者的最佳判断，患有症状性内脏疾病或任何使患者不适合内分泌治疗的疾病负担的患者
  • CNS 转移患者。
  • 根据国家癌症研究所 (NCI) 不良事件通用术语标准 (CTCAE) 4.03 版 ≤1 级，尚未解决与先前抗癌治疗相关的临床和实验室急性毒性的患者。
  • 患者有已知的人类免疫缺陷病毒 (HIV) 感染史（检测不是强制性的）。
  • 有临床意义的、不受控制的心脏病和/或心脏复极化异常
  • 患者目前正在接受方案中定义的任何物质，并且不能在治疗开始前 7 天停止：

对于绝经前队列：

  • 孕妇或哺乳期妇女。
  • 有生育能力的女性，定义为所有生理上能够怀孕的女性，除非她们在研究治疗药物给药期间和停止研究药物治疗后 21 天内使用高效避孕方法。

注意：本研究不允许使用口服（雌激素和黄体酮）、透皮、注射或植入激素避孕方法以及激素替代疗法。

对于绝经后队列：

-接受过晚期乳腺癌的任何先前全身抗癌治疗（包括激素治疗和化疗）的患者。

注意：接受新（辅助）乳腺癌治疗的患者符合条件。 如果先前的新（辅助）治疗包括来曲唑或阿那曲唑，则从治疗完成到随机分组的无病间隔必须大于 12 个月。

- 在随机化之前接受 ≤ 14 天来曲唑或阿那曲唑治疗晚期疾病的患者符合条件。

其他协议定义的包含/排除可能适用。

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
实验性的：Ribociclib

Patients in premenopausal and postmenopausal cohorts were randomized in a 1:1 ratio to either the experimental arm or the control arm.

Premenopausal experimental arm:

Non-steroidal aromatase inhibitor (NSAI) + Goserelin + Ribociclib. For premenopausal patients only, the patient was an adult female who was ≥ 18 years old and < 60 years old at the time of providing informed consent. The choice of non-steroidal aromatase inhibitor was based on the investigator's assessment of the patient's past medical history.

Postmenopausal experimental arm:

Letrozole + Ribociclib.

Pharmacokinetic (PK) Cohort:

Open-label treatment with Ribociclib + Letrozole combination. For postmenopausal patients only, the patient was an adult female who was ≥ 18 years old at the time of providing informed consent.
药品：NSAI：来曲唑或阿那曲唑

来曲唑：口服片剂，每日 2.5mg（每个周期的所有天数，不间断）。

阿那曲唑：口服片剂，每天 1mg（每个周期的所有天数，不间断） 对于绝经前队列，研究者根据患者既往病史选择 NSAI。

对于绝经后和 PK 队列，所有患者都将服用来曲唑。

药品：戈舍瑞林
皮下植入，每 28 天周期的第 1 天 3.6 毫克
药品：Ribociclib
Film-coated tablets for oral use (200 mg x 3) from days 1 to 21 of each 28 day cycle.
其他名称：
  • LEE011
安慰剂比较：Ribociclib Placebo

Patients in premenopausal and postmenopausal cohorts were randomized in a 1:1 ratio to either the experimental arm or the control arm.

Premenopausal control arm:

Non-steroidal aromatase inhibitor (NSAI) + Goserelin + Placebo. For premenopausal patients only, the patient was an adult female who was ≥ 18 years old and < 60 years old at the time of providing informed consent. The choice of non-steroidal aromatase inhibitor was based on the investigator's assessment of the patient's past medical history.

Postmenopausal control arm:

Letrozole + Placebo. For postmenopausal patients only, the patient was an adult female who was ≥ 18 years old at the time of providing informed consent.
药品：NSAI：来曲唑或阿那曲唑

来曲唑：口服片剂，每日 2.5mg（每个周期的所有天数，不间断）。

阿那曲唑：口服片剂，每天 1mg（每个周期的所有天数，不间断） 对于绝经前队列，研究者根据患者既往病史选择 NSAI。

对于绝经后和 PK 队列，所有患者都将服用来曲唑。

药品：戈舍瑞林
皮下植入，每 28 天周期的第 1 天 3.6 毫克
药品：Ribociclib Placebo
Film-coated tablets for oral use (200 mg x 3) from days 1 to 21 of each 28 day cycle.
其他名称：
  • LEE011 安慰剂

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Pre and Postmenopausal Cohorts: Progressive Free Survival (PFS) Based on Local Assessment by RECIST 1.1 Guideline
大体时间：After approximately 100 progression-free survival (PFS) events had been observed in each cohort, using data collected up to the analysis cut-off date of 25-Apr-2022, an average of 43 months.
Progression-free survival (PFS) was defined as the time from randomization to the first documented disease progression or death from any cause. PFS was assessed by local investigators based on tumor evaluations using RECIST version 1.1 criteria. Patients who had not experienced progression or death by the analysis cut-off date of 25 April 2022 were censored at the date of their last adequate tumor assessment prior to that cut-off.
After approximately 100 progression-free survival (PFS) events had been observed in each cohort, using data collected up to the analysis cut-off date of 25-Apr-2022, an average of 43 months.

次要结果测量

结果测量
措施说明
大体时间
PK Cohort: Maximum Observed Plasma Concentration (Cmax) of Ribociclib and Its Metabolite LEQ803
大体时间：Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.
Venous whole blood samples were collected for activity-based pharmacokinetic characterization. The maximum plasma concentration (Cmax) was listed and summarized using descriptive statistics. Actual sampling times were taken into consideration for the pharmacokinetic analysis.
Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.
PK Cohort: Time to Maximum Observed Plasma Concentration (Tmax) of Ribociclib and Its Metabolite LEQ803
大体时间：Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.
Venous whole blood samples were collected for activity-based pharmacokinetic characterization. The time to reach maximum plasma concentration (Tmax) was listed and summarized using descriptive statistics. Actual sampling times were taken into consideration for the pharmacokinetic analysis.
Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.
PK Cohort: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24h) of Ribociclib and Its Metabolite LEQ803
大体时间：Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.
Venous whole blood samples were collected for activity-based pharmacokinetic characterization. The area under the concentration-time curve from time zero to 24 hours post-dose (AUC₀-₂₄h) was listed and summarized using descriptive statistics. Actual sampling times were taken into consideration for the pharmacokinetic analysis.
Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.
Pre and Postmenopausal Cohorts: Overall Survival (OS)
大体时间：Up to approximately 80 months
Overall Survival (OS) was defined as the time from date of first dose to date of death due to any cause. If a participant was not known to have died, then OS was censored at the latest date the participant was known to be alive (on or before the cut-off date).
Up to approximately 80 months
Pre and Postmenopausal Cohorts: Overall Response Rate (ORR)
大体时间：Up to approximately 80 months

Overall Response Rate (ORR) was defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) by Investigator assessment as per RECIST 1.1 criteria:

  • CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
  • PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Up to approximately 80 months
Pre and Postmenopausal Cohorts: Clinical Benefit Rate (CBR)
大体时间：Up to approximately 80 months

Clinical Benefit Rate (CBR) was defined as the proportion of patients achieving a complete response (CR) or partial response (PR) per RECIST 1.1 criteria, or stable disease (SD) lasting at least 24 weeks, based on Investigator assessment using RECIST 1.1 criteria:

  • CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
  • PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
  • SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for Progressive Disease (PD).
Up to approximately 80 months
Pre and Postmenopausal Cohorts: Time To Response (TTR)
大体时间：Up to approximately 80 months
Time to Response (TTR) was defined as the duration from randomization to the first documented evidence of either a complete response (CR) (the disappearance of all target and non-target lesions) or a partial response (PR) (at least a 30% reduction in the sum of the longest diameters of target lesions from baseline) as assessed by the investigator.
Up to approximately 80 months
Pre and Postmenopausal Cohorts: Duration of Response (DoR)
大体时间：Up to approximately 80 months
Duration of Response (DoR) only applies to participants whose Best Overall Response (BOR) was complete response (CR) or partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date is the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to any cause. Participants continuing without progression or death were censored at the date of their last adequate tumor assessment.
Up to approximately 80 months
Pre and Postmenopausal Cohorts: Time to Definitive Deterioration of ECOG Performance Status From Baseline
大体时间：Baseline up to approximately 43 months
Time to definitive deterioration in ECOG performance status was defined as the time from the date of randomization to the date when ECOG performance status had definitively deteriorated by at least 1 category compared with baseline. Deterioration was considered definitive if there was no subsequent improvement in ECOG performance status back to the baseline category or above. The ECOG performance status scale assesses a patient's functional level, ranging from 0 (fully active) to 5 (dead). Patients were censored if no definitive deterioration in ECOG performance status was observed before the first to occur between: (i) the analysis cut-off date, and (ii) the date when a new anti-neoplastic therapy was started. The censoring date was the date of the last performance status assessment prior to cut-off/start of new anti-neoplastic therapy. Time to definitive deterioration of ECOG performance status from baseline was estimated by using the Kaplan-Meier method.
Baseline up to approximately 43 months

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Novartis Pharmaceuticals

调查人员

  • 研究主任：Novartis Pharmaceuticals、Novartis Pharmaceuticals

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2018年8月29日

初级完成 (实际的)

2022年4月25日

研究完成 (实际的)

2025年5月9日

研究注册日期

首次提交

2018年9月12日

首先提交符合 QC 标准的

2018年9月12日

首次发布 (实际的)

2018年9月14日

研究记录更新

最后更新发布 (实际的)

2026年7月8日

上次提交的符合 QC 标准的更新

2026年6月11日

最后验证

2026年6月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • CLEE011A2206

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

诺华致力于与合格的外部研究人员共享患者水平数据的访问权限，并支持符合条件的研究的临床文件。 这些请求由独立审查小组根据科学价值审查和批准。 所提供的所有数据均已匿名处理，以根据适用的法律法规尊重参与试验的患者的隐私。

此试验数据的可用性是根据 www.clinicalstudydatarequest.com 上描述的标准和过程

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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