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Alpelisib 加奥拉帕尼治疗铂类耐药/难治性高级别浆液性卵巢癌，未检测到胚系 BRCA 突变

2026年6月3日 更新者：Novartis Pharmaceuticals

EPIK-O：一项 III 期、多中心、随机 (1:1)、开放标签、主动控制的研究，旨在评估 Alpelisib (BYL719) 联合奥拉帕尼与单药细胞毒性化疗相比的疗效和安全性, 在未检测到种系 BRCA 突变、铂类耐药或难治性高级别浆液性卵巢癌的参与者中

本研究的目的是评估 alpelisib 和奥拉帕尼联合治疗与单药细胞毒性化疗相比，对铂耐药或难治性高级别浆液性卵巢癌患者的疗效和安全性，未检测到种系 BRCA 突变。

研究概览

地位

终止

条件

干预/治疗

详细说明

这项研究将包括患有铂耐药或难治性高级别浆液性卵巢癌的成年女性，未检测到种系 BRCA 突变。 在这项开放标签的主动对照研究中，参与者将以 1:1 的比例随机分配至 alpelisib 加奥拉帕尼或单药细胞毒性化疗（紫杉醇或 PLD）。

参与者将继续接受研究治疗，直到疾病进展、无法接受进一步治疗的不可接受的毒性，或直到由于任何其他原因停止研究治疗。 停止治疗后，所有参与者将进入治疗后随访期，包括安全性随访和 9 周的进展后随访。 一旦完成治疗后随访，参与者将进入生存随访期。

研究类型

介入性

注册 (实际的)

358

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

  • 中国
      • Beijing、中国、100036
        • Novartis Investigative Site
      • Jinan、中国、250012
        • Novartis Investigative Site
      • Shanghai、中国、200032
        • Novartis Investigative Site
      • Tianjin、中国、300480
        • Novartis Investigative Site
    • Sichuan
      • Chengdu、Sichuan、中国、610041
        • Novartis Investigative Site
  • 丹麦
      • Herlev、丹麦、DK-2730
        • Novartis Investigative Site
      • Odense C、丹麦、5000
        • Novartis Investigative Site
  • 俄罗斯
      • Arkhangelsk、俄罗斯、163045
        • Novartis Investigative Site
  • 加拿大
    • Alberta
      • Calgary、Alberta、加拿大、T2N 5G2
        • Novartis Investigative Site
    • British Columbia
      • Vancouver、British Columbia、加拿大、V5Z 4E6
        • Novartis Investigative Site
    • Ontario
      • London、Ontario、加拿大、N6A 5W9
        • Novartis Investigative Site
      • Toronto、Ontario、加拿大、M4N 3M5
        • Novartis Investigative Site
  • 台湾
      • Taichung、台湾、407219
        • Novartis Investigative Site
      • Taipei、台湾、10002
        • Novartis Investigative Site
      • Taipei、台湾、11217
        • Novartis Investigative Site
  • 土耳其（türkiye）
      • Ankara、土耳其（türkiye）、06520
        • Novartis Investigative Site
    • Karsiyaka
      • Izmir、Karsiyaka、土耳其（türkiye）、35575
        • Novartis Investigative Site
    • Sihhiye-Altindag
      • Ankara、Sihhiye-Altindag、土耳其（türkiye）、06230
        • Novartis Investigative Site
    • Yuregir
      • Adana、Yuregir、土耳其（türkiye）、01230
        • Novartis Investigative Site
  • 墨西哥
      • Mexico City、墨西哥、04700
        • Novartis Investigative Site
    • Nuevo León
      • Monterrey、Nuevo León、墨西哥、64460
        • Novartis Investigative Site
  • 奥地利
      • Graz、奥地利、8036
        • Novartis Investigative Site
    • Tyrol
      • Innsbruck、Tyrol、奥地利、6020
        • Novartis Investigative Site
  • 巴西
    • Minas Gerais
      • Belo Horizonte、Minas Gerais、巴西、30130-100
        • Novartis Investigative Site
    • São Paulo
      • São Paulo、São Paulo、巴西、04014-002
        • Novartis Investigative Site
  • 德国
      • Berlin、德国、13353
        • Novartis Investigative Site
      • Essen、德国、45136
        • Novartis Investigative Site
    • Baden-Wurttemberg
      • Mannheim、Baden-Wurttemberg、德国、68305
        • Novartis Investigative Site
    • Saxony
      • Dresden、Saxony、德国、01307
        • Novartis Investigative Site
  • 意大利
      • Milan、意大利、20141
        • Novartis Investigative Site
      • Naples、意大利、80131
        • Novartis Investigative Site
    • BO
      • Bologna、BO、意大利、40138
        • Novartis Investigative Site
    • FI
      • Florence、FI、意大利、50134
        • Novartis Investigative Site
    • MI
      • Milan、MI、意大利、20133
        • Novartis Investigative Site
    • RM
      • Roma、RM、意大利、00168
        • Novartis Investigative Site
    • VI
      • Vicenza、VI、意大利、36100
        • Novartis Investigative Site
  • 捷克语
      • Nový Jičín、捷克语、741 01
        • Novartis Investigative Site
      • Prague、捷克语、128 08
        • Novartis Investigative Site
    • Poruba
      • Ostrava、Poruba、捷克语、708 52
        • Novartis Investigative Site
  • 斯洛伐克
      • Bratislava、斯洛伐克、83310
        • Novartis Investigative Site
  • 新加坡
      • Singapore、新加坡、119074
        • Novartis Investigative Site
      • Singapore、新加坡、168583
        • Novartis Investigative Site
  • 比利时
      • Brussels、比利时、1000
        • Novartis Investigative Site
      • Leuven、比利时、3000
        • Novartis Investigative Site
      • Namur、比利时、5000
        • Novartis Investigative Site
  • 法国
      • Besançon、法国、25030
        • Novartis Investigative Site
      • Lyon、法国、69373
        • Novartis Investigative Site
      • Paris、法国、75012
        • Novartis Investigative Site
      • Pierre-Bénite、法国、69495
        • Novartis Investigative Site
      • Villejuif、法国、94800
        • Novartis Investigative Site
  • 澳大利亚
      • Sydney、澳大利亚、2031
        • Novartis Investigative Site
    • South Australia
      • Bedford Park、South Australia、澳大利亚、5041
        • Novartis Investigative Site
    • Victoria
      • Shepparton、Victoria、澳大利亚、3630
        • Novartis Investigative Site
  • 美国
    • Arizona
      • Phoenix、Arizona、美国、85016
        • Arizona Oncology Associates
      • Phoenix、Arizona、美国、85016
        • HonorHealth
    • Florida
      • Fort Myers、Florida、美国、33901
        • Florida Cancer Specialists
      • West Palm Beach、Florida、美国、33401
        • Florida Cancer Specialists
    • Maryland
      • Silver Spring、Maryland、美国、20904
        • Maryland Oncology Hematology P A
    • Massachusetts
      • Boston、Massachusetts、美国、02114
        • Massachusetts General Hospital
      • Boston、Massachusetts、美国、02115
        • Dana Farber Cancer Institute
    • New York
      • New York、New York、美国、10065
        • Memorial Sloan Kettering Cancer Ctr
    • Ohio
      • Cincinnati、Ohio、美国、45267
        • University of Cincinnati
      • Cincinnati、Ohio、美国、45242
        • Oncology Hematology Care Inc
    • South Dakota
      • Sioux Falls、South Dakota、美国、57106
        • Avera Cancer Institute
    • Tennessee
      • Nashville、Tennessee、美国、37203
        • Tennessee Oncology
    • Texas
      • Amarillo、Texas、美国、79124
        • Texas Oncology
      • Bedford、Texas、美国、76022
        • Texas Oncology P A
      • San Antonio、Texas、美国、78217
        • Texas Oncology P A
      • Tyler、Texas、美国、75702
        • Texas Oncology Northeast Texas
  • 芬兰
      • Kuopio、芬兰、FIN-70211
        • Novartis Investigative Site
      • Tampere、芬兰、FIN-33521
        • Novartis Investigative Site
      • Turku、芬兰、FIN 20521
        • Novartis Investigative Site
  • 英国
      • Glasgow、英国、G12 0YN
        • Novartis Investigative Site
      • London、英国、SE1 9RT
        • Novartis Investigative Site
      • Manchester、英国、M20 2BX
        • Novartis Investigative Site
  • 荷兰
      • Eindhoven、荷兰、5623 EJ
        • Novartis Investigative Site
  • 葡萄牙
      • Loures、葡萄牙、2674-514
        • Novartis Investigative Site
      • Porto、葡萄牙、4200-072
        • Novartis Investigative Site
  • 西班牙
      • Barcelona、西班牙、08035
        • Novartis Investigative Site
      • Barcelona、西班牙、08036
        • Novartis Investigative Site
      • Córdoba、西班牙、14004
        • Novartis Investigative Site
      • Madrid、西班牙、28034
        • Novartis Investigative Site
      • Valencia、西班牙、46010
        • Novartis Investigative Site
    • Navarre
      • Pamplona、Navarre、西班牙、31008
        • Novartis Investigative Site
  • 阿根廷
      • Buenos Aires、阿根廷、C1012AAR
        • Novartis Investigative Site
      • Caba、阿根廷、C1015ABO
        • Novartis Investigative Site
    • Buenos Aires
      • CABA、Buenos Aires、阿根廷、C1125ABD
        • Novartis Investigative Site
  • 韩国
      • Seoul、韩国、03080
        • Novartis Investigative Site
      • Seoul、韩国、03722
        • Novartis Investigative Site
  • 马来西亚
      • Kuala Lumpur、马来西亚、59100
        • Novartis Investigative Site
    • Kuala Lumpur
      • Kuala Lumpur、Kuala Lumpur、马来西亚、50586
        • Novartis Investigative Site
    • Sabah
      • Kota Kinabalu、Sabah、马来西亚、88996
        • Novartis Investigative Site
    • Sarawak
      • Kuching、Sarawak、马来西亚、93586
        • 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

纳入标准：

  • 参与者经组织学确诊为高级别浆液性或高级别子宫内膜样卵巢癌、输卵管癌或原发性腹膜癌
  • 可测量的疾病，即根据 RECIST 1.1 标准至少有一个可测量的病灶（如果自照射后有明显的进展迹象，则先前照射部位的病灶只能算作目标病灶）
  • 如果不存在可测量的疾病，则应根据 CA-125 的妇科癌症组间标准 (GCIC) 评估该疾病
  • 根据 FDA 批准的检测方法确定，参与者没有种系 BRCA1/2 突变。
  • 参与者的东部肿瘤合作组 (ECOG) 表现状态为 0 或 1
  • 根据GCIG 第 5 届卵巢癌共识会议定义。 基于铂的化疗方案不一定是参与者在进入研究之前接受的最后一个方案。
  • 参与者必须接受过至少一种但不超过三种先前的全身治疗方案，并且单药化疗适合作为下一步治疗。
  • 参与者有足够的骨髓和器官功能

排除标准：

  • 参与者之前接受过任何 PI3K、mTOR 或 AKT 抑制剂的治疗。
  • 参与者同时使用其他抗癌疗法
  • 参与者处于小肠或大肠梗阻状态或有其他胃肠 (GI) 功能受损或胃肠道疾病
  • 参与者在开始研究药物前 14 天内接受过手术或尚未从主要副作用中恢复
  • 参与者尚未从与先前抗癌治疗相关的所有毒性 5 恢复到基线或 NCI CTCAE 版本 4.03 等级≤1。 此标准的例外情况：允许任何级别的脱发参与者进入研究。
  • 肝功能受损且 Child Pugh 评分为 B 或 C 的参与者
  • 参与者在随机分组前接受了 ≤ 4 周的放射治疗或 ≤ 2 周的姑息性有限野放疗，并且尚未从此类治疗的相关副作用（脱发除外）恢复到基线、1 级或更好。
  • 参与者已知对任何研究药物或赋形剂过敏

其他纳入/排除标准可能适用

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：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Alpelisib+olaparib
Alpelisib (200 mg once daily after food) and Olaparib (200 mg twice daily) were both administered orally on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28-day cycle.
药品：Alpelisib
Alpelisib was administered at 200 mg orally once daily following food on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28-day cycle
其他名称：
  • BYL719
药品：Olaparib
Olaparib was administered at 200 mg orally twice daily irrespective of meals on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28-day cycle.
有源比较器：Paclitaxel or Pegylated liposomal doxorubicin
Paclitaxel (80 mg/m²) was administered as a weekly intravenous infusion on Days 1, 8, 15, and 22 of each 28-day cycle, or Pegylated liposomal doxorubicin (40-50 mg/m² at physician discretion) was administered as an intravenous infusion once every 28 days starting on Cycle 1 Day 1.
药品：Paclitaxel
Paclitaxel (80 mg/m²) was administered as a weekly intravenous infusion on Days 1, 8, 15, and 22 of each 28-day cycle.
药品：Pegylated liposomal doxorubicin (PLD)
Pegylated liposomal doxorubicin (40-50 mg/m² at physician discretion) was administered as an intravenous infusion once every 28 days starting on Cycle 1 Day 1.

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) Based on Blinded Independent Review Committee (BIRC) Assessment Using RECIST 1.1 Criteria
大体时间：From randomization until the date of the first documented progression or death due to any cause, whichever comes first, assessed up to approximately 21 months

Progression-free survival (PFS) was defined as the time from randomization to the first documented disease progression or death from any cause, as determined by blinded independent review committee (BIRC) assessment. Participants without an event were censored at the date of their last adequate tumor assessment. Clinical deterioration without objective radiologic evidence was not considered disease progression in the primary efficacy analysis.

Disease progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, as a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (including baseline), with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of non-target lesions.
From randomization until the date of the first documented progression or death due to any cause, whichever comes first, assessed up to approximately 21 months

次要结果测量

结果测量
措施说明
大体时间
Overall Survival
大体时间：From randomization until death, assessed up to approximately 44 months
Overall survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a participant is not known to have died, then OS will be censored at the latest date the participant was known to be alive
From randomization until death, assessed up to approximately 44 months
Overall Response Rate (ORR) With Confirmed Response Based on BIRC Assessment According to RECIST 1.1 Criteria
大体时间：Up to approximately 21 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 blinded independent review committee (BIRC) 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 21 months
Clinical Benefit Rate (CBR) With Confirmed Response Based on BIRC Assessment According to RECIST 1.1
大体时间：Up to approximately 21 months
Clinical benefit rate (CBR) with confirmed response was defined as the percentage of participants whose best overall response was a confirmed CR or PR, or stable disease (SD) maintained for at least 24 weeks. CR, PR, and SD were determined by BIRC according to RECIST 1.1 criteria.
Up to approximately 21 months
Time to Response (TTR) Based on BIRC Assessment and According to RECIST 1.1
大体时间：From the date of randomization to the first documented response, assessed through Month 12
Time to response (TTR) was defined as the interval from randomization to the first documented occurrence of either complete response (CR) or partial response (PR), which was subsequently confirmed (using the date of initial response, not the confirmation date). CR and PR were determined based on tumor response data assessed by BIRC according to RECIST 1.1 criteria.
From the date of randomization to the first documented response, assessed through Month 12
Duration of Response (DOR) With Confirmed Response Based on BIRC Assessment and According to RECIST 1.1
大体时间：From first documented response to first documented progression or death, assessed up to approximately 21 months
Duration of response (DOR) with confirmed response was calculated only for participants whose best overall response was a confirmed complete response (CR) or confirmed partial response (PR), based on tumor response data assessed by BIRC according to RECIST 1.1. The start date was the date of the first documented CR or PR (i.e., the initial response date, not the confirmation date), and the end date was the date of first documented disease progression or death due to underlying cancer. Participants without progression or cancer-related death were censored at the date of their last adequate tumor assessment.
From first documented response to first documented progression or death, assessed up to approximately 21 months
Time to Definitive Deterioration of the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
大体时间：Up to approximately 18 months
Performance status (PS) was evaluated using the ECOG scale, which comprises six grades (0 to 5), where 0 represents fully active and 5 represents death. Time to definitive deterioration in ECOG PS was defined as the interval from randomization to the date when ECOG PS worsened by at least one category from baseline and remained worsened. Deterioration was considered definitive if there was no subsequent improvement to the baseline category or better. Participants were censored if no definitive deterioration occurred before the earlier of: (i) the analysis cut-off date or (ii) initiation of a new anti-neoplastic therapy. The censoring date was the date of the last PS assessment prior to the cut-off or start of new therapy.
Up to approximately 18 months
Number of Participants With Dose Interruptions and Dose Reductions
大体时间：From randomization until end of treatment, assessed up to approximately 18 months
The number of participants with dose reductions/interruptions was assessed and summarized by study treatment.
From randomization until end of treatment, assessed up to approximately 18 months
Dose Intensity for Alpelisib and Olaparib
大体时间：From randomization until end of treatment, assessed up to approximately 18 months
Dose intensity was computed as the ratio of actual cumulative dose received to actual duration of exposure and summarized by study treatment.
From randomization until end of treatment, assessed up to approximately 18 months
Dose Intensity for Paclitaxel
大体时间：From randomization until end of treatment, assessed up to approximately 18 months
Dose intensity was computed as the ratio of actual cumulative dose received to actual duration of exposure and summarized by study treatment.
From randomization until end of treatment, assessed up to approximately 18 months
Dose Intensity for Pegylated Liposomal Doxorubicin
大体时间：From randomization until end of treatment, assessed up to approximately 18 months
Dose intensity was computed as the ratio of actual cumulative dose received to actual duration of exposure and summarized by study treatment.
From randomization until end of treatment, assessed up to approximately 18 months
Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of Alpelisib and Olaparib
大体时间：Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)
The AUCtau will be assessed to characterize the pharmacokinetics of alpelisib when administered in combination of olaparib
Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)
Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast)of Alpelisib and Olaparib
大体时间：Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)
The AUClast will be assessed to characterize the pharmacokinetics of alpelisib when administered in combination of olaparib
Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)
Maximum Concentration (Cmax) of Alpelisib and Olaparib
大体时间：Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)
The Cmax will be assessed to characterize the pharmacokinetics of alpelisib when administered in combination of olaparib
Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)
Time to Reach Maximum Concentration (Tmax) of Alpelisib and Olaparib
大体时间：Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)
The Tmax will be assessed to characterize the pharmacokinetics of alpelisib when administered in combination of olaparib
Day 8 Cycle 1 (pre-dose, 1, 2, 3, 4, 6, 8 and 24 hours post dose), Day 1 on Cycle 2, 4 and 8 (pre-dose)
Time to Definitive Deterioration by 10% in FACT-O Trial Outcomes Index (TOI) Score
大体时间：Baseline, up to 15 months
The Functional Assessment of Cancer Therapy-Ovarian (FACT O) is a validated instrument that evaluates quality of life in patients with ovarian cancer. The Trial Outcome Index (TOI) of the FACT-O combines Physical Well Being (PWB), Functional Well Being (FWB), and the Ovarian Cancer Subscale (OCS), and its scores range from 0 to 100, with higher scores indicating better quality of life and physical/functional status. Time to definitive deterioration by 10% in FACT O TOI is defined as the time from randomization to the first occurrence of at least a 10% worsening from baseline with no subsequent improvement above this threshold, or death. Participants without an event before analysis cut off or before starting another anticancer therapy were censored at their last adequate assessment. Time to deterioration was estimated using the Kaplan-Meier method.
Baseline, up to 15 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

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

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)

2021年7月22日

初级完成 (实际的)

2023年4月21日

研究完成 (实际的)

2026年1月19日

研究注册日期

首次提交

2021年1月25日

首先提交符合 QC 标准的

2021年1月25日

首次发布 (实际的)

2021年1月28日

研究记录更新

最后更新发布 (实际的)

2026年6月4日

上次提交的符合 QC 标准的更新

2026年6月3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

  • CBYL719K12301
  • 2024-510782-42-00 (注册表标识符：EU CT Number)

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

是的

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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