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HR+ HER2 阴性 aBC 绝经后女性接受 Ribociclib 和来曲唑一线治疗以及 PIK3CA 突变患者接受 Alpelisib 加氟维司群二线治疗的分子特征研究 (BioItaLEE)

2026年6月12日 更新者：Novartis Pharmaceuticals

一项关于激素受体阳性 (HR+) HER2 阴性晚期乳腺癌绝经后妇女接受 Ribociclib 加来曲唑一线治疗和 PIK3CA 突变患者的分子特征的 IIIb 期、开放标签、局部、多中心研究, 关于 Alpelisib Plus Fulvestrant (BioItaLEE) 的二线治疗

该临床试验的目的是研究激素受体阳性 (HR+) HER2 阴性晚期乳腺癌绝经后妇女在接受瑞博西尼和来曲唑一线治疗以及 PIK3CA 突变患者接受第二线治疗时的分子特征- alpelisib 加氟维司群的线治疗

研究概览

地位

终止

条件

干预/治疗

详细说明

这项本地多中心研究的主要目的是研究在 ribociclib 进展之前和之后、核心阶段期间以及在 alpelisib 进展之前和之后肿瘤的遗传和基因表达改变，从而确定突变模式，它们如何演变，及其与 CDK4/6 抑制和结果（如持续反应或早期进展）的关联。 该研究还旨在评估药物基因组学及其与不良事件（频率和严重程度）、药物相互作用和临床结果的关联。

最后，该研究还将在这个特定的意大利人群中产生额外的长期安全性和有效性数据。

研究类型

介入性

注册 (实际的)

287

阶段

  • 第三阶段

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

  • 意大利
      • Naples、意大利、80131
        • Novartis Investigative Site
      • Naples、意大利、80138
        • Novartis Investigative Site
    • AL
      • Casale Monferrato、AL、意大利、15033
        • Novartis Investigative Site
    • BA
      • Bari、BA、意大利、70124
        • Novartis Investigative Site
    • BG
      • Bergamo、BG、意大利、24127
        • Novartis Investigative Site
    • BN
      • Benevento、BN、意大利、82100
        • Novartis Investigative Site
    • BO
      • Bologna、BO、意大利、40138
        • Novartis Investigative Site
    • BR
      • Brindisi、BR、意大利、72100
        • Novartis Investigative Site
    • BS
      • Brescia、BS、意大利、25123
        • Novartis Investigative Site
    • CR
      • Cremona、CR、意大利、26100
        • Novartis Investigative Site
    • CT
      • Catania、CT、意大利、95124
        • Novartis Investigative Site
      • Catania、CT、意大利、95123
        • Novartis Investigative Site
    • FE
      • Cona、FE、意大利、44100
        • Novartis Investigative Site
    • FG
      • San Giovanni Rotondo、FG、意大利、71013
        • Novartis Investigative Site
    • GE
      • Genova、GE、意大利、16132
        • Novartis Investigative Site
    • LI
      • Livorno、LI、意大利、57124
        • Novartis Investigative Site
    • MB
      • Monza、MB、意大利、20900
        • Novartis Investigative Site
    • MC
      • Province of Macerata、MC、意大利、62100
        • Novartis Investigative Site
    • ME
      • Messina、ME、意大利、98158
        • Novartis Investigative Site
    • MI
      • Milan、MI、意大利、20133
        • Novartis Investigative Site
      • Milan、MI、意大利、20141
        • Novartis Investigative Site
      • Milan、MI、意大利、20132
        • Novartis Investigative Site
      • Rozzano、MI、意大利、20089
        • Novartis Investigative Site
    • NU
      • Nuoro、NU、意大利、08100
        • Novartis Investigative Site
    • PA
      • Palermo、PA、意大利、90127
        • Novartis Investigative Site
      • Palermo、PA、意大利、90146
        • Novartis Investigative Site
    • PD
      • Padova、PD、意大利、35100
        • Novartis Investigative Site
    • PG
      • Perugia、PG、意大利、06129
        • Novartis Investigative Site
    • PI
      • Pisa、PI、意大利、56126
        • Novartis Investigative Site
    • PN
      • Aviano、PN、意大利、33081
        • Novartis Investigative Site
    • PO
      • Prato、PO、意大利、59100
        • Novartis Investigative Site
    • PU
      • Fano、PU、意大利、61032
        • Novartis Investigative Site
    • RA
      • Faenza、RA、意大利、48018
        • Novartis Investigative Site
    • RM
      • Roma、RM、意大利、00168
        • Novartis Investigative Site
      • Roma、RM、意大利、00128
        • Novartis Investigative Site
      • Roma、RM、意大利、00189
        • Novartis Investigative Site
    • SA
      • Salerno、SA、意大利、84131
        • Novartis Investigative Site
    • TO
      • Candiolo、TO、意大利、10060
        • Novartis Investigative Site
      • Torino、TO、意大利、10128
        • Novartis Investigative Site
    • UD
      • Udine、UD、意大利、33100
        • Novartis Investigative Site
    • VR
      • Negrar、VR、意大利、37024
        • 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 及以上 (成人、年长者)

接受健康志愿者

不

描述

核心阶段纳入标准：

  • 患者在一线治疗中患有晚期（局部复发或转移性）乳腺癌（晚期情况未接受过治疗）。
  • 患者处于绝经后，定义为以下之一：
  • 既往双侧卵巢切除术
  • 年龄≥60
  • 年龄 <60 岁和闭经 12 个月或更长时间（在没有化疗、他莫昔芬、托瑞米芬或卵巢抑制的情况下）并且 FSH 和雌二醇在绝经后范围内符合当地正常范围
  • 患者在组织学和/或细胞学上经当地实验室确诊为雌激素受体阳性和/或孕激素受体阳性乳腺癌。
  • 患者患有 HER2 阴性乳腺癌，定义为原位杂交试验阴性或 IHC 状态为 0、1+ 或 2+。 如果 IHC 为 2+，则当地实验室检测需要进行阴性原位杂交（FISH、CISH 或 SISH）检测。
  • 患者愿意按照协议中的计划为生物学评估/目标采集血液和肿瘤样本。

核心阶段排除标准：

  • 先前接受过任何 CDK4/6 抑制剂治疗的患者。
  • 接受过任何先前全身性激素治疗或晚期乳腺癌化疗的患者。

笔记：

接受过乳腺癌新/辅助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，则从治疗完成到进入研究的无病间隔必须大于 12 个月。

• 在纳入本试验之前接受≤ 28 天来曲唑或阿那曲唑治疗晚期疾病的患者符合条件。

- 患者目前正在使用其他抗癌疗法。 其他协议定义的包含/排除标准可能适用。

扩展阶段纳入标准：

  • 患者已停止（任何允许的原因）在核心阶段使用 ribociclib + 来曲唑治疗，并被认为适合二线使用 alpelisib + 氟维司群治疗。 Ribociclib + letrozole 必须是 alpelisib + fulvestrant 之前的最后一个治疗方案。
  • 诺华指定实验室在肿瘤组织和/或血浆中确定患者具有 PIK3CA 突变。 在核心阶段（筛选或 EOT）获得的组织样本的结果是可以接受的

扩展阶段排除标准：

  • 患者之前接受过任何 PI3K 抑制剂治疗。
  • 患者同时使用其他抗癌疗法。 核心阶段使用的 Ribociclib 和来曲唑必须在扩展研究治疗的第一天前至少 7 天停用。

所有具有重叠毒性的药物必须在 7 天内停用，并且 AE 在研究治疗之前解决为 NCI CTCAE v4.03 ≤ 1 级。 此标准的例外情况：允许患有任何级别脱发的患者进入研究。

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：不适用
  • 介入模型：顺序分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：ribociclib+来曲唑
Ribociclib 口服（服用 3 周/停药 1 周）与每日一次口服来曲唑组合：600 毫克片剂瑞博西尼 QD + 2.5 毫克片剂来曲唑 QD
药品：核糖体
Ribociclib 口服（服用 3 周/停药 1 周）与每日一次口服来曲唑组合：600 毫克片剂瑞博西尼 QD + 2.5 毫克片剂来曲唑 QD
其他名称：
  • LEE011
药品：来曲唑
Ribociclib 口服（服用 3 周/停药 1 周）与每日一次口服来曲唑组合：600 毫克片剂瑞博西尼 QD + 2.5 毫克片剂来曲唑 QD
实验性的：alpelisib+氟维司群
Alpelisib 300 mg 每天口服连续给药方案与氟维司群 500 mg 肌肉注射，在第 1 个周期的第 1 天和第 15 天，以及此后每个周期的第 1 天，以 28 天为周期
药品：阿尔培利西布
Alpelisib 300 mg 每天口服连续给药方案与氟维司群 500 mg 肌肉注射，在第 1 个周期的第 1 天和第 15 天，以及此后每个周期的第 1 天，以 28 天为周期
其他名称：
  • BYL719
药品：氟维司群
Alpelisib 300 mg 每天口服连续给药方案与氟维司群 500 mg 肌肉注射，在第 1 个周期的第 1 天和第 15 天，以及此后每个周期的第 1 天，以 28 天为周期

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
Progression-Free Survival (PFS) by Cycle 1 Day 15 Complete Mutational Dynamic Change
大体时间：Up to approximately 5.7 years
PFS: Time (months) from start of the study treatment to first documented progression or death due to any cause, whichever came first. Kaplan-Meier estimates. Persistent Wild Type: Wild Type (or single nucleotide polymorphisms [SNPs] only) at screening without hotspot mutations at any later assessment. Confirmed cleared: Mutated, with 100% decrease in target mutation variant allele frequency (VAF) at C1D15 or at C2D1 also observed at FI. Unconfirmed cleared: Mutated that cleared or at C1D15 or at C2D1 that were not cleared at FI. Late cleared: Mutated without 100% decrease in target mutation VAF at C1D15 and at C2D1 with 100% decrease in target mutation VAF at FI. New mutated: Wild Type ( [SNPs] only) at screening with hotspot mutations at C1D15 or C2D1. Late mutated: Wild Type patients (or SNPs only) at screening without hotspot mutations at C1D15 and C2D1 with hotspot mutations at FI. Confirmed mutated: Mutated without 100% decrease in target mutation VAF at any later assessment.
Up to approximately 5.7 years
Number of Participants With Progression-Free Survival (PFS) Events by Cycle 1 Day 15 Complete Mutational Dynamic Change
大体时间：Up to approximately 5.7 years
Kaplan-Meier estimates. Persistent Wild Type: Wild Type (or single nucleotide polymorphisms [SNPs] only) at screening without hotspot mutations at any later assessment. Confirmed cleared: Mutated, with 100% decrease in target mutation variant allele frequency (VAF) at C1D15 or at C2D1 also observed at FI. Unconfirmed cleared: Mutated that cleared or at C1D15 or at C2D1 that were not cleared at FI. Late cleared: Mutated without 100% decrease in target mutation VAF at C1D15 and at C2D1 with 100% decrease in target mutation VAF at FI. New mutated: Wild Type ( [SNPs] only) at screening with hotspot mutations at C1D15 or C2D1. Late mutated: Wild Type patients (or SNPs only) at screening without hotspot mutations at C1D15 and C2D1 with hotspot mutations at FI. Confirmed mutated: Mutated without 100% decrease in target mutation VAF at any later assessment.
Up to approximately 5.7 years
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
大体时间：Up to approximately 5.7 years
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. The data row labels below refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Up to approximately 5.7 years
Percent Change From Screening in Target Mutation Variant Allele Frequency (VAF)
大体时间：Up to approximately 5.7 years
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
Up to approximately 5.7 years
Number of Participants With Partial Response (PR) in the Extension Phase
大体时间：Up to approximately 1.6 years
PR was assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1, criteria and was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the screening sum of diameters.
Up to approximately 1.6 years

次要结果测量

结果测量
措施说明
大体时间
Percent Change From Screening in Thymidine Kinase 1 (TK1) Serum Level
大体时间：Up to approximately 5.7 years
Up to approximately 5.7 years
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
大体时间：Up to approximately 5.7 years
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Up to approximately 5.7 years
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
大体时间：Up to approximately 5.7 years
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Up to approximately 5.7 years
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Long Responders
大体时间：Up to approximately 5.7 years
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
Up to approximately 5.7 years
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Early Progressors
大体时间：Up to approximately 5.7 years
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
Up to approximately 5.7 years
Number of Screening Hotspot Mutations Per De Novo Patient in Liquid Biopsy Samples and Tissue Samples
大体时间：Up to approximately 5.7 years
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Up to approximately 5.7 years
Number of Screening Hotspot Mutations Per Recurrent Patient in Liquid Biopsy Samples and Tissue Samples
大体时间：Up to approximately 5.7 years
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Up to approximately 5.7 years
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at Screening
大体时间：Up to approximately 5.7 years
Results data refer to the total number of evaluations (i.e. the number of participants in the biomarker analysis set with both valid baseline liquid biopsy and tissue sample multiplied by 39 considered genes).
Up to approximately 5.7 years
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at End of Treatment
大体时间：Up to approximately 5.7 years
Results data refer to the total number of evaluations (i.e. the number of participants in the biomarker analysis set with both valid baseline liquid biopsy and tissue sample multiplied by 39 considered genes).
Up to approximately 5.7 years
Time to Progression (TTP)
大体时间：Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
Time to progression (TTP) was defined as time from date of start of treatment to the date of event defined as the first documented progression or death due to underlying cancer.
Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
Percentage of Participants With Best Overall Response Rate of Complete Response (CR) or Partial Response (PR)
大体时间：Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR): (CR+PR) per Response Evaluation Criteria in Solid Tumors (RECIST), v. 1.1. 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.
Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
Percentage of Participants With Clinical Benefit Rate
大体时间：Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
Clinical benefit rate (CBR) was defined as the percentage of participants with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. Per RECIST v. 1.1, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.
Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
Change From Baseline Tumor Mutational Burden (TMB) to Progression of Disease During the Core and Extension Phases
大体时间：Up to approximately 5.7 years
Up to approximately 5.7 years
Change From Baseline Tumor Microenvironment Parameters to Progression of Disease During the Core and Extension Phases
大体时间：Up to approximately 5.7 years
Up to approximately 5.7 years

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

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2月2日

初级完成 (实际的)

2023年12月11日

研究完成 (实际的)

2023年12月11日

研究注册日期

首次提交

2018年1月29日

首先提交符合 QC 标准的

2018年2月13日

首次发布 (实际的)

2018年2月20日

研究记录更新

最后更新发布 (实际的)

2026年7月10日

上次提交的符合 QC 标准的更新

2026年6月12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

  • CLEE011AIT01
  • 2017-004176-62 (EudraCT编号)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

未定

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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