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Phase 2 Study of AMG 386 Plus Paclitaxel With or Without Bevacizumab as First Line Therapy in Her2-Negative Breast Cancer Patients

2015年10月7日 更新者：Amgen

A Randomized, 4-Arm, Placebo-Controlled Phase 2 Trial of AMG 386 in Combination With Bevacizumab and Paclitaxel or AMG 386 Plus Paclitaxel as First-Line Therapy in Subjects With Her2-Negative, Metastatic or Locally Recurrent Breast Cancer

This is a phase 2, randomized, placebo controlled, multi-center study to estimate the treatment effect and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel and paclitaxel/bevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer.

AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.

研究概览

地位

完全的

条件

干预/治疗

详细说明

Primary Objective: To estimate the treatment effect as measured by progression free survival (PFS) of subjects receiving AMG 386 (at 2 doses) in combination with paclitaxel + bevacizumab relative to paclitaxel + bevacizumab + placebo.

Secondary Objective(s):

  • To compare the treatment effect as measured by PFS of subjects receiving open-label AMG 386 in combination with paclitaxel relative to paclitaxel + bevacizumab + placebo
  • To compare the treatment effect as measured by PFS of subjects receiving AMG 386 in combination with paclitaxel and bevacizumab relative to paclitaxel + AMG 386
  • To evaluate the safety and tolerability of the combination and non-bevacizumab regimens
  • To estimate other measures (RR, DOR, TTR, TTP) of treatment effect
  • To evaluate the pharmacokinetics (PK) of AMG 386 and bevacizumab when used in combination
  • To estimate the incidence of anti-AMG386 antibody formation

Exploratory Objective(s):

  • To explore the pharmacodynamic (PD) response as assessed by changes in blood levels of angiogenic cytokines, tumor apoptosis, and other markers
  • To explore the association of histological features and selected immunologic, biochemical, pharmacogenetic, or angiogenic markers in tumor biopsies, plasma, or serum samples with safety and/or efficacy outcomes

Study Design:

This is a phase 2, randomized, placebo controlled, multi-center study to estimate the treatment effect and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel and paclitaxel/bevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer.

Two hundred twenty subjects will be randomized 1:1:1:1 to each of the following arms:

Arm A: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW Arm B: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW Arm C: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW Arm D: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW To maintain the double-blind in arms A, B, and C, each subject will be infused weekly with a volume of investigational product equivalent to 10 mg/kg AMG 386 IV. Arm D will receive open label AMG 386 and will not receive a placebo for bevacizumab.

Subjects will be discontinued from study treatment at any time for radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death.

Subjects alive at the time of discontinuation of all study medications will be followed for up to 48 months from the date of the last subject enrolled into the trial to evaluate overall survival.

Radiological imaging to assess disease status will be performed every 8 weeks ± 7 days (2 cycles) for 2 years and then every 4 months ± 1 month thereafter during the study until subjects develop radiographic disease progression per the modified RECIST criteria. In addition, any subject who discontinues study drug treatment prior to disease progression will continue to have radiological imaging performed every 8 weeks ± 7 days during the long term follow up period if the subject has not been in the study for 2 years until the subject develops radiographic disease progression or begins a new treatment. If the subject has been on study for 2 years, radiological imaging every 4 months ± 1 month will be performed during long term follow-up period until the subject develops radiographic disease progression or begins a new treatment.

The overall study design is described by a study schema immediately following this synopsis. Amgen Global Safety (AGS) will charter a data review team (DRT) that is independent of the team conducting the study and will review unblinded safety data after 20, 40, and 80 subjects have been randomized and have had the opportunity to receive at least 1 cycle (4 weeks) of study treatment.

研究类型

介入性

注册 (实际的)

228

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

  • 丹麦
      • Herlev、丹麦、2730
        • Research Site
  • 匈牙利
      • Gyula、匈牙利、5700
        • Research Site
      • Kaposvar、匈牙利、7400
        • Research Site
      • Szombathely、匈牙利、9700
        • Research Site
      • Veszprem、匈牙利、8200
        • Research Site
  • 印度
    • Karnataka
      • Bangalore、Karnataka、印度、560 029
        • Research Site
    • Maharashtra
      • Miraj、Maharashtra、印度、416 410
        • Research Site
      • Mumbai、Maharashtra、印度、400 012
        • Research Site
      • Nagpur、Maharashtra、印度、440 012
        • Research Site
      • Pune、Maharashtra、印度、411 001
        • Research Site
    • Rajasthan
      • Jaipur、Rajasthan、印度、302 013
        • Research Site
      • Jaipur、Rajasthan、印度、302 004
        • Research Site
  • 奥地利
      • Innsbruck、奥地利、6020
        • Research Site
      • Wels、奥地利、4600
        • Research Site
      • Wien、奥地利、1090
        • Research Site
  • 比利时
      • Leuven、比利时、3000
        • Research Site
      • Liege、比利时、4000
        • Research Site
      • Wilrijk、比利时、2610
        • Research Site
  • 法国
      • La Roche Sur Yon Cedex 9、法国、85925
        • Research Site
      • Lyon、法国、69008
        • Research Site
      • Marseille、法国、13009
        • Research Site
      • Montpellier Cedex 5、法国、34298
        • Research Site
      • Paris Cedex 20、法国、75020
        • Research Site
      • Paris Cedex 5、法国、75248
        • Research Site
      • Toulouse Cedex、法国、31052
        • Research Site
      • Vandoeuvre les Nancy、法国、54511
        • Research Site
  • 波兰
      • Gdansk、波兰、80-952
        • Research Site
      • Lubin、波兰、59-300
        • Research Site
      • Poznan、波兰、61-485
        • Research Site
      • Warszawa、波兰、02-781
        • Research Site
      • Warszawa、波兰、04-141
        • Research Site
      • Wroclaw、波兰、53-413
        • Research Site
  • 澳大利亚
    • South Australia
      • Kurralta Park、South Australia、澳大利亚、5037
        • Research Site
    • Victoria
      • Epping、Victoria、澳大利亚、3076
        • Research Site
      • Fitzroy、Victoria、澳大利亚、3065
        • Research Site
      • Footscray、Victoria、澳大利亚、3011
        • Research Site
      • Malvern、Victoria、澳大利亚、3144
        • Research Site
    • Western Australia
      • Perth、Western Australia、澳大利亚、6000
        • Research Site
  • 美国
    • Arizona
      • Litchfield Park、Arizona、美国、85340
        • Research Site
      • Tucson、Arizona、美国、85724
        • Research Site
    • Arkansas
      • Hot Springs、Arkansas、美国、71913
        • Research Site
      • Little Rock、Arkansas、美国、72205
        • Research Site
    • California
      • Campbell、California、美国、95008
        • Research Site
      • Los Angeles、California、美国、90095
        • Research Site
      • Murrieta、California、美国、92562
        • Research Site
      • Santa Maria、California、美国、93454
        • Research Site
    • Connecticut
      • New Haven、Connecticut、美国、06520
        • Research Site
      • Stamford、Connecticut、美国、06902
        • Research Site
    • Florida
      • Orlando、Florida、美国、32804
        • Research Site
    • Minnesota
      • Robbinsdale、Minnesota、美国、55422
        • Research Site
    • Nevada
      • Henderson、Nevada、美国、89052
        • Research Site
    • New Hampshire
      • Lebanon、New Hampshire、美国、03756
        • Research Site
      • Nashua、New Hampshire、美国、03061
        • Research Site
    • New Jersey
      • Edison、New Jersey、美国、08820
        • Research Site
      • Mountain Lakes、New Jersey、美国、07046
        • Research Site
    • North Carolina
      • Asheville、North Carolina、美国、28806
        • Research Site
      • Charlotte、North Carolina、美国、28203
        • Research Site
    • Pennsylvania
      • Hershey、Pennsylvania、美国、17033
        • Research Site
      • Philadelphia、Pennsylvania、美国、19106
        • Research Site
    • South Carolina
      • Columbia、South Carolina、美国、29210
        • Research Site
    • Texas
      • Richardson、Texas、美国、75080
        • Research Site
      • San Antonio、Texas、美国、78229
        • Research Site
      • Sugar Land、Texas、美国、77479
        • Research Site
    • Utah
      • Ogden、Utah、美国、84403
        • Research Site
  • 芬兰
      • Helsinki、芬兰、00029
        • Research Site
  • 英国
      • Guildford、英国、GU2 7XX
        • Research Site
      • Leicester、英国、LE1 5WW
        • Research Site
      • London、英国、W6 8RF
        • Research Site
      • London、英国、NW1 2PG
        • Research Site
      • Manchester、英国、M20 4BX
        • Research Site
      • Northwood、英国、HA6 2RN
        • Research Site
      • Nottingham、英国、NG5 1PB
        • Research Site
  • 荷兰
      • Maastricht、荷兰、6229 HX
        • Research Site
  • 西班牙
      • Madrid、西班牙、28033
        • Research Site
    • AndalucÃ-a
      • Jaén、AndalucÃ-a、西班牙、23007
        • Research Site
    • Cataluña
      • Sabadell、Cataluña、西班牙、08208
        • Research Site
    • Galicia
      • Santiago de Compostela、Galicia、西班牙、15706
        • Research 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

是的

有资格学习的性别

女性

描述

Inclusion Criteria:

  • Subjects must have histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
  • Measurable or non-measurable disease per modified RECIST guidelines
  • ECOG of 0 or 1 (within 14 days prior to randomization)

  • Adequate organ and hematological function as evidenced by the following laboratory studies within 14 days prior to randomization:

    • Cardiac function, as follows:

  • Normal sinus rhythm (no significant ECG changes)
  • Left ventricular ejection fraction ≥ LLN, as determined by echocardiogram or MUGA scan, according to institutional standards within 28 days prior to randomization

Exclusion Criteria:

  • Inflammatory Breast Cancer
  • Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 peripheral neuropathy > grade 1 at randomization
  • History of arterial or venous thrombosis, including transient ischemic attack (TIA), within 1 year prior to randomization
  • Adjuvant or neoadjuvant taxane treatment within 12 months of randomization. Any other adjuvant chemotherapy regimen must be discontinued at least 21 days prior to randomization
  • Prior chemotherapy, vaccine, or biological therapy for locally recurrent or metastatic breast cancer (prior endocrine therapy is permitted)
  • Prior radiation therapy, radiofrequency ablation, percutaneous cryotherapy or hepatic chemoembolization on all sites of disease unless disease progression was subsequently documented 14 days prior to randomization.
  • Overexpression of HER-2 (gene amplification by FISH or 3+ over expression by immunohistochemistry).
  • Current or prior history of central nervous system metastasis
  • History of bleeding diathesis or clinically significant bleeding within 6 months prior to randomization
  • Major surgical procedure within 28 days prior to randomization
  • Open breast biopsy within 14 days prior to randomization
  • Minor surgical procedure, placement of access device, or fine needle aspiration within 7 days of first dose
  • Prior malignancy (other than thyroid cancer, in situ cervical cancer, or basal cell cancer of the skin, treated with curative intent and without evidence of disease for ≥ 3 years prior to randomization)
  • Clinically significant cardiac disease within 12 months prior to randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication
  • Non-healing wound, ulcer or fracture
  • Known hypersensitivity to paclitaxel or drugs using the vehicle cremophor
  • Known hypersensitivity to bacterial proteins, or any of the drugs required in this study
  • Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen
  • Known active or chronic hepatitis
  • Uncontrolled hypertension as defined as systolic blood pressure ≥ 150 mm Hg and diastolic blood pressure ≥ 90 mm Hg. Anti-hypertensive medications are allowed if the subject is stable on their current dose at the time of randomization
  • Currently or previously treated with any VEGF or VEGFr inhibitor, including but not limited to, bevacizumab, SU11248 (sunitinib), PTK787 (vatalinib), AZD 2171, AEE-788, BAY 43-9006 (sorafenib) and AMG 706.
  • Treatment with coumarin-type anticoagulants, (other than low dose prophylaxis for central venous catheters ≤ 1mg/day) within 7 days prior to randomization
  • Currently or previously treated with angiopoietin inhibitors, or inhibitors of TIE-1 or TIE-2 including, but not limited to, AMG 386, XL880, XL820
  • Treatment with immune modulators such as cyclosporine and tacrolimus within 30 days prior to randomization
  • Concomitant therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (SERMS), given for breast cancer prevention or for osteoporosis. Subjects must have discontinued these agents 28 days prior to randomization
  • Pregnant (ie, positive beta-human chorionic gonadotropin test) or is breast feeding

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：A
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW
药品：AMG 386
AMG 386 3mg/kg IV QW [blinded]
药品：Bevacizumab
Bevacizumab 10mg/kg IV Q2W
药品：AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
药品：AMG 386
AMG 386 10mg/kg IV QW [blinded]
药品：Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
实验性的：D
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW
药品：AMG 386
AMG 386 3mg/kg IV QW [blinded]
药品：AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
药品：AMG 386
AMG 386 10mg/kg IV QW [blinded]
药品：Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
实验性的：B
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW
药品：AMG 386
AMG 386 3mg/kg IV QW [blinded]
药品：Bevacizumab
Bevacizumab 10mg/kg IV Q2W
药品：AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
药品：AMG 386
AMG 386 10mg/kg IV QW [blinded]
药品：Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
有源比较器：C
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW
药品：Bevacizumab
Bevacizumab 10mg/kg IV Q2W
药品：Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
药品：AMG 386 Placebo
AMG 386 Placebo [blinded]

研究衡量的是什么？

主要结果指标

结果测量
大体时间
Progression-free survival (PFS)
大体时间：3 YEARS
3 YEARS

次要结果测量

结果测量
大体时间
Objective Response (OR)
大体时间：3 YEARS
3 YEARS
Duration of Response (DOR)
大体时间：3 YEARS
3 YEARS
Time to response
大体时间：3 YEARS
3 YEARS
Overall Survival
大体时间：3 YEARS
3 YEARS
Time to progression (TTP)
大体时间：3 YEARS
3 YEARS
Incidence of AEs and significant laboratory changes
大体时间：3 YEARS
3 YEARS
AMG 386 Pharmakokinetic parameters
大体时间：3 YEARS
3 YEARS
Incidence of the occurrence of anti-AMG 386 antibody formation
大体时间：3 YEARS
3 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

Amgen

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

有用的网址

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

2007年7月1日

初级完成 (实际的)

2010年8月1日

研究完成 (实际的)

2014年5月1日

研究注册日期

首次提交

2007年8月2日

首先提交符合 QC 标准的

2007年8月2日

首次发布 (估计)

2007年8月3日

研究记录更新

最后更新发布 (估计)

2015年10月29日

上次提交的符合 QC 标准的更新

2015年10月7日

最后验证

2015年10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

  • 20060341

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