Study Of Lapatinib In Patients With Relapsed Or Refractory Inflammatory Breast Cancer
2015年9月24日 更新者：GlaxoSmithKline
A Phase II Study to Evaluate the Efficacy, Safety and Pharmacodynamics of Lapatinib in Patients With Relapsed or Refractory Inflammatory Breast Cancer
This study was designed to determine how effective and safe a new investigational drug, lapatinib, is in treating patients with treatment refractory or relapsed inflammatory breast cancer.
Tumor tissue collected pre-treatment and at Day 28 will be examined for biologic activity by IHC (immunohistochemistry).
Treatment will consist of daily oral therapy with lapatinib.
A patient may continue treatment as long as they are receiving benefit.
Blood samples for hematology and chemistry panels, MUGA/ECHO (multigated acquisition/echocardiogram) exams and physical exams will be performed throughout the study to monitor safety.
研究概览
详细说明
This Phase II open label, multicenter study is designed to evaluate the efficacy, safety, and pharmacodynamic effects of oral lapatinib administered as a single agent therapy to patients with relapsed or refractory inflammatory breast cancer.
Eligible patients must have a diagnosis of inflammatory breast cancer based on clinicopathologic criteria, tumor that is readily accessible for biopsy, and must have previously received treatment with an anthracycline and taxane-containing regimen (30 patients) plus trastuzumab (90 patients).
Patients enrolled must have tumors that overexpress ErbB2, with or without co-expression of ErbB1.
The primary objective for this study is to evaluate the objective response rate (defined as complete response plus partial response).
Secondary objectives are to evaluate clinical benefit including quality of life parameters, progression-free survival, overall survival, time-to-response, response duration, safety and tolerability, pharmacodynamic effects on intracellular mediators that regulate tumor cell growth and survival, as well as effects on proteomic profile, and circulating levels of extracellular domains of ErbB1 and ErbB2 in peripheral blood.
研究类型
介入性
注册 (实际的)
126
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
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Ramat Gan、以色列、52621
- GSK Investigational Site
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Zrifin、以色列、70300
- GSK Investigational Site
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Ontario
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Toronto、Ontario、加拿大、M4N 3M5
- GSK Investigational Site
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Bruxelles、比利时、1000
- GSK Investigational Site
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Bayonne、法国、64100
- GSK Investigational Site
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Lyon Cedex 08、法国、69373
- GSK Investigational Site
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Marseille Cedex 09、法国、13273
- GSK Investigational Site
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Paris Cedex 20、法国、75970
- GSK Investigational Site
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Paris Cedex 5、法国、75248
- GSK Investigational Site
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Saint-Herblain、法国、44805
- GSK Investigational Site
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Sfax、突尼斯、3000
- GSK Investigational Site
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Sfax、突尼斯、3029
- GSK Investigational Site
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Tunis、突尼斯、1007
- GSK Investigational Site
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Tunis、突尼斯、1004
- GSK Investigational Site
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Florida
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Miami、Florida、美国、33136-1002
- GSK Investigational Site
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Illinois
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Chicago、Illinois、美国、60637
- GSK Investigational Site
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Zion、Illinois、美国、60099
- GSK Investigational Site
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Maryland
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Bethesda、Maryland、美国、20892-1201
- GSK Investigational Site
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Michigan
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Detroit、Michigan、美国、48201
- GSK Investigational Site
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Missouri
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St. Louis、Missouri、美国、63110
- GSK Investigational Site
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North Carolina
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Durham、North Carolina、美国、27710
- GSK Investigational Site
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Washington
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Seattle、Washington、美国、98109
- GSK Investigational Site
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London、英国、SW3 6JJ
- GSK Investigational Site
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Barcelona、西班牙、08036
- GSK Investigational Site
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Barcelona、西班牙、08035
- GSK Investigational Site
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Girona、西班牙、17007
- GSK Investigational Site
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Madrid、西班牙、28041
- GSK Investigational Site
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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:
- Must have a life expectancy of at least 12 weeks.
- Has a left ventricular ejection fraction (LVEF) ≥ 50%, or ≥ lower limit of normal for the institution, based on ECHO or MUGA.
- Aspartate and alanine transaminase (AST or ALT) ≤ 3 times the upper limit of the reference range (patients with liver metastases may have AST and ALT ≤ 5 times the upper limit of the reference range and may be enrolled).
- Total bilirubin ≤ 3.0 mg/dL.
- Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance (CrCl) ≥ 30 mL/min
- Adequate bone marrow function. Hemoglobin ≥ 9 gm/dL. Absolute granulocyte count ≥ 1,500/mm³ (1.5 x 10^9/L). Platelets ≥ 75,000/mm³ (100 x 10^9/L).
- Recovered or stabilized sufficiently from side effects associated with previous chemotherapy, surgery or radiotherapy.
- Provided written informed consent.
- ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.
- Able to swallow and retain oral medication.
- Male or female, if female:
A female is eligible to enter and participate in the study if she is of:
- Non-childbearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal); or
- Childbearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility. This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate), has a negative serum pregnancy test at screening, and agrees to one of the following where considered acceptable to the local IRB/IEC: Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm).
Abstinence from sexual intercourse from 2 weeks prior to administration of the investigational product, throughout the active study treatment period, and through the post-treatment follow-up visit (to occur 28 days after last dose of investigational product).
Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject.
Implants of levonorgestrel. Injectable progestogen. Any intrauterine device (IUD) with a documented failure rate of less than 1% per year.
Oral contraceptives (either combined or progestogen only). Barrier methods including diaphragm or condom with a spermicide.
- At least 18 years of age.
- Has either measurable disease by Response Evaluation Criteria in Solid Tumors (RESIST) or clinically evaluable skin disease. Measurable lesions may be in the field of prior adjuvant irradiation; however, there must be at least an 8 week period between the last radiation treatment and the baseline scan documenting disease status for the lesion to be measurable.
- Tumor that is accessible for biopsy.
- Tumor that overexpresses ErbB2 defined as 3+ by IHC or FISH +. The ErbB 2 overexpression must be documented prior to dosing.
- Documented disease progression or relapse following treatment, which must have contained a taxane and anthracycline-containing regimen in the adjuvant or metastatic setting (30 patients) plus trastuzumab (90 patients)
- Histological diagnosis of breast carcinoma with a clinical diagnosis of IBC based on the presence of inflammatory changes in the involved breast, including diffuse erythema and edema (peau d'orange), with or without an underlying palpable mass involving the majority of the skin of the breast. Pathologic evidence of dermal lymphatic invasion should be noted but is not required for diagnosis.
Exclusion criteria:
- Is clinically assessed to have inadequate venous access for protocol-related blood draws.
- Has a clinically significant electrocardiogram (ECG) abnormality.
- Has Class II to IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- Has physiological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- Is currently receiving oral steroid treatment (inhaled steroids are permitted), or any other medication on the prohibited medications list
- Is currently receiving amiodarone or has received amiodarone in the 6 months prior to screening.
- Has received chemotherapy, immunotherapy, biologic therapy or hormonal therapy within the past 14 days, with the exception of mitomycin C within the past 6 weeks.
- Has received treatment with any investigational drug in the previous 4 weeks.
- Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the investigational product. These include other anilinoquinazolines, such as gefitinib [Iressa], erlotinib [Tarceva], or other chemically related compounds.
- Is considered medically unfit for the study by the investigator as a result of the medical interview, physical exam, or screening investigations.
- Has evidence of symptomatic or uncontrolled brain metastases or leptomeningeal disease. Patients with brain metastases treated by surgery and/or radiotherapy are eligible if neurologically stable and do not require steroids or anticonvulsants.
- Has malabsorption syndrome, a disease affecting gastrointestinal function, or resection of the stomach or small bowel.
- Is a pregnant or lactating female.
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 |
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实验性的：Lapatinib
Single arm study of lapatinib with no comparator arm.
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Tyrosine kinase inhibitor administered daily at 1500 mg/kg
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研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
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Objective Response rate (complete response plus partial response)
大体时间：Week 84
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Week 84
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次要结果测量
结果测量 |
大体时间 |
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Clinical benefit (progression free survival, time to progression, response duration)
大体时间：week 84
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week 84
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Assessment of clinical benefit, defined as CR or PR for at least 4 weeks, or SD for at least 6 months
大体时间：week 84
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week 84
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Calculation of progression-free survival, defined as the time between the first dose of investigational product and the first documented sign of disease progression or death.
大体时间：week 84
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week 84
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Calculation of time-to-response, defined as the time between the first dose of investigational product and the first documented CR or PR.
大体时间：week 84
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week 84
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Calculation of duration of response, defined as the time from initial documented CR or PR to the first documented sign of disease progression.
大体时间：week 84
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week 84
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Evaluation of changes in QoL and pain scale measurements collected on Day 1 and every 4 weeks while receiving study treatment.
大体时间：week 84
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week 84
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Evaluation of adverse events (AEs), changes in laboratory values and echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) results from pre-dose, during dosing and post-dose assessments
大体时间：week 84
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week 84
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Comparison of the effects of lapatinib on biomarkers that are involved in regulating tumor cell proliferation and survival (e.g., phosphorylated forms of Erk1/2 and Akt, STAT3, S6 Kinase, Bad, truncated ErbB2 and potentially other downstream mediators of
大体时间：Day 28
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Day 28
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tumor cell growth and survival) by quantitative IHC and by direct and genome-wide methods (e.g., direct sequencing and DNA microarray) in tumor tissue collected prior to and following 28 days of lapatinib monotherapy.
大体时间：Day 28
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Day 28
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Examination of the effects of lapatinib therapy on the levels of circulating ErbB1 and ErbB2 ECD and the proteomic profile of peripheral blood. Investigation of the use of FDG-PET to predict early response to treatment with lapatinib.
大体时间：Day 28
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Day 28
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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。
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
- Kaufman B, Trudeau M, Awada A, Blackwell K, Bachelot T, Salazar V, DeSilvio M, Westlund R, Zaks T, Spector N, Johnston S. Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory inflammatory breast cancer: final results and survival of the expanded HER2+ cohort in EGF103009, a phase II study. Lancet Oncol. 2009 Jun;10(6):581-8. doi: 10.1016/S1470-2045(09)70087-7. Epub 2009 Apr 24.
- Kaufman B, Wu Y, Amonkar MM, Sherrill B, Bachelot T, Salazar V, Viens P, Johnston S. Impact of lapatinib monotherapy on QOL and pain symptoms in patients with HER2+ relapsed or refractory inflammatory breast cancer. Curr Med Res Opin. 2010 May;26(5):1065-73. doi: 10.1185/03007991003680323.
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
2005年3月1日
初级完成 (实际的)
2007年9月1日
研究完成 (实际的)
2010年5月1日
研究注册日期
首次提交
2005年3月18日
首先提交符合 QC 标准的
2005年3月18日
首次发布 (估计)
2005年3月21日
研究记录更新
最后更新发布 (估计)
2015年9月28日
上次提交的符合 QC 标准的更新
2015年9月24日
最后验证
2015年5月1日
更多信息
与本研究相关的术语
关键字
其他研究编号
- EGF103009
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.