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A Phase 1/2 Study Of HKI-272 (Neratinib) in Combination With Trastuzumab (Herceptin) In Subjects With Advanced Breast Cancer

2018年6月26日 更新者：Puma Biotechnology, Inc.

A Phase I/II Study of HKI-272 in Combination With Trastuzumab (Herceptin) in Subjects With Advanced Breast Cancer

The purpose of this study is to determine the safety and efficacy of HKI-272 (neratinib) in combination with trastuzumab in patients with advanced breast cancer.

研究概览

地位

完全的

条件

干预/治疗

详细说明

Open label phase 1/2 study of ascending multiple oral doses of HKI-272 in combination with IV trastuzumab in subjects with advanced human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Three to six subjects will be enrolled in each dose group. Adverse events and dose limiting toxicities will be assessed from the first dose of study drug though day 21. When the maximum tolerated dose (MTD) of HKI-272 plus trastuzumab is determined, an additional 30 subjects will be enrolled at that dose level, and followed for progression free survival for approximately 1 year.

研究类型

介入性

注册 (实际的)

45

阶段

  • 阶段2
  • 阶段1

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、100853
        • Chinese PLA General Hospital
      • Beijing、中国、100021
        • Cancer Hospital, Academy of Med Science and Peking Union Med
      • Beijing、中国、100071
        • 307 Hospital of Chinese People's Liberation Army
    • Jiangsu
      • Nanjing、Jiangsu、中国、210002
        • Chinese Nanjing Bayi Hospital
    • Tianjin
      • Tianjin、Tianjin、中国、300121
        • Tianjin Union Medicine Center
  • 法国
      • Paris、法国、75005
        • Institut Curie
      • Saint-Herblain、法国、44805
        • Centre Rene Gauducheau
  • 瑞士
      • Lausanne、瑞士、CH-1011
        • Centre Hospitalier Universitaire Vaudois
  • 美国
    • California
      • Duarte、California、美国、91010-3000
        • City of Hope National Medical Center
      • Los Angeles、California、美国、90033
        • LAC/USC Medical Center, USC/Norris Comprehensive Cancer Center
      • Pasadena、California、美国、91105
        • City of Hope National Medical Center
    • Maryland
      • Baltimore、Maryland、美国、21201
        • University of Maryland, University of Maryland Medical Center
    • North Carolina
      • Durham、North Carolina、美国、27710
        • Duke University, Duke University Medical Center
    • Pennsylvania
      • Philadelphia、Pennsylvania、美国、19111
        • Fox Chase Cancer Center

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

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Pathologic diagnosis of breast cancer with current stage IIIB, IIIC or IV not curable by available therapy
  • Progression following at least one Herceptin-containing cytotoxic chemotherapy regimen (neoadjuvant, adjuvant, or metastatic setting)
  • HER2 positive breast cancer
  • At least one measurable target lesion
  • Adequate performance status
  • Adequate cardiac, kidney, and liver function
  • Adequate blood counts
  • Willingness of all subjects who are not surgically sterile or post menopausal to use acceptable methods of birth control

Exclusion Criteria:

  • More than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease
  • Major surgery, chemotherapy, radiotherapy, investigational agents, Herceptin or other cancer therapy within 2 weeks of treatment day 1
  • Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2
  • Extensive visceral disease
  • Active central nervous system metastases
  • Pregnant or breast feeding women
  • Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom
  • Prior exposure to HKI-272 or other HER2 targeted agents (except Herceptin and Tykerb)
  • Significant cardiac disease or dysfunction
  • History of life-threatening hypersensitivity to Herceptin
  • Inability or unwillingness to swallow HKI-272 capsules
  • Any other cancer within 5 years with the exception of contralateral breast cancer, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin

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：非随机化
  • 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：Part 1 - dose level 1 (160 mg)
All subjects receiving HKI-272 dose level 1 in combination with trastuzumab
药品：HKI-272
HKI-272 by mouth
其他名称：
  • neratinib
药品：trastuzumab
trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter
其他名称：
  • 赫赛汀
实验性的：Part 1 - dose level 2 (240 mg)
All subjects receiving HKI-272 dose level 2 in combination with trastuzumab
药品：HKI-272
HKI-272 by mouth
其他名称：
  • neratinib
药品：trastuzumab
trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter
其他名称：
  • 赫赛汀
实验性的：Part 2 - expanded MTD cohort
All subjects receiving HKI-272 in combination with trastuzumab
药品：HKI-272
HKI-272 by mouth
其他名称：
  • neratinib
药品：trastuzumab
trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter
其他名称：
  • 赫赛汀

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
16-week Progression-free Survival (PFS) Rate
大体时间：From first dose date to progression status (PD or death) at 16-week
16-week progression-free survival (PFS) rate for subjects with advanced breast cancer who receive neratinib at the maximum tolerated dose (MTD) in combination with trastuzumab, evaluable population.
From first dose date to progression status (PD or death) at 16-week

次要结果测量

结果测量
措施说明
大体时间
Objective Response Rate (ORR)
大体时间：From first dose date to progression or last tumor assessment, up to five and a half years.
Percentage of participants with partial response (PR) or complete response (CR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.
From first dose date to progression or last tumor assessment, up to five and a half years.
Duration of Response (DOR)
大体时间：From start date of response to first PD, assessed up to five and half years after the first subject was randomized
Duration of response was measured from the time at which response criteria were met for complete response (CR) or partial response (PR) (whichever status was recorded first) until the first date on which recurrence or PD was objectively documented, taking as the reference for PD the smallest measurements recorded since the test article administration started.
From start date of response to first PD, assessed up to five and half years after the first subject was randomized
Progression Free Survival (PFS)
大体时间：From first dose date to progression or death, assessed up to five and half years.
Progression Free Survival was measured from the date of the first dose of test article until the first date on which recurrence or progression, or death due to any cause, was documented, censored at the last evaluation, investigator assessment.
From first dose date to progression or death, assessed up to five and half years.
Clinical Benefit Rate (CBR)
大体时间：From first dose date to progression or last tumor assessment, assessed up to five and half years.
The percentage of participants with a best overall response of a complete response (CR) or partial response (PR) or stable disease (SD) >=24 weeks.
From first dose date to progression or last tumor assessment, assessed up to five and half years.
Area Under the Curve of Neratinib Concentration
大体时间：Prior to the first dose, and at hours 1, 2, 4, 6, 8 and 24 on days 22.
Area Under the Curve of Neratinib concentration at day 22 following Administration of Neratinib 240 mg in combination with Trastuzumab 2 mg/kg in Subjects with Cancer.
Prior to the first dose, and at hours 1, 2, 4, 6, 8 and 24 on days 22.
Terminal-phase Elimination Half-life of Neratinib in Combination With Trastuzumab.
大体时间：Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6
Terminal-phase elimination half-life of Neratinib at day 22 following Administration of Neratinib 240 mg in combination with Trastuzumab 2 mg/kg to Subjects with Cancer.
Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6

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

Puma Biotechnology, Inc.

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)

2007年4月4日

初级完成 (实际的)

2009年7月31日

研究完成 (实际的)

2018年3月2日

研究注册日期

首次提交

2006年11月9日

首先提交符合 QC 标准的

2006年11月9日

首次发布 (估计)

2006年11月10日

研究记录更新

最后更新发布 (实际的)

2018年7月24日

上次提交的符合 QC 标准的更新

2018年6月26日

最后验证

2018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

  • 3144A1-202 / B1891013

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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