Understanding Mechanisms of Acquired Resistance to BIBW2992
2018年3月5日 更新者:Lecia V. Sequist、Massachusetts General Hospital
In this research study we are looking to see how effective BIBW 2992 is at suppressing the development of the T790M mutation in non-small cell lung cancer (NSCLC) patients.
Epidermal growth factor receptors (EGFR) are proteins found on the surface of some cancer cells that promote a growth signal.
Some cancer drugs for NSCLC work to block this signal from reaching its target on the cancer cells which in turn may slow or stop the cancer from growing.
However, many times patients with EGFR mutations will stop responding to these cancer drugs and develop drug-resistance because they have developed a specific EGFR mutation called T790M.
BIBW 2992 may prevent the T790M mutation from becoming active and therefore slow disease progression.
研究概览
详细说明
- Participants will take tablets of BIBW 2992 once a day during each cycle. Each cycle is 28 days (4 weeks).
- Participants will come to the clinic on Day 1, 8 and 15 of Cycle 1. For Cycle 2 through 8, they will need to come to the clinic on Day 1. After Cycle 8, they will have study visits every 2 months.
- The following tests and procedures will be performed at these clinic visits: physical examination, routine blood tests, research blood samples, EKG (every fourth cycle starting cycle 5), ECHO or MUGA (every fourth cycle starting cycle 5), an assessment of the tumor by CT or MRI scan (every 8 weeks).
- Participants may continue to participate in this research study as long as their tumor does not grow and their disease does not worsen and they do not have any severe side effects.
- Participants will have a tumor biopsy performed at the end of their participation in this study if their tumor is growing or if they have a new tumor. The purpose of this biopsy is to assess for the presence or the absence of the mutation T790M.
研究类型
介入性
注册 (实际的)
24
阶段
- 不适用
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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Massachusetts
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Boston、Massachusetts、美国、02114
- Massachusetts General Hospital
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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:
- Participants must have histologically or cytologically confirmed stage IIIB, IV or recurrent non-small cell lung cancer
- A somatic mutation in epidermal growth factor receptor (EGFR) must be present as documented by a CLIA-certified laboratory
- There must be radiographic measurable or evaluable disease
- Participants must be willing, at the time of signing consent, to agree to a future biopsy of their tumor tissue at the time of disease progression, provided such a biopsy is safe and feasible at that time.
- Performance status must be 0, 1 or 2 on the Eastern Cooperative Oncology Group scale
- 18 years of age or older
- Normal organ and marrow function as outlined in the protocol
- Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
Exclusion Criteria:
- Prior EGFR tyrosine kinase inhibitor therapy (including gefitinib, erlotinib, or any experimental EGFR TKI agents)
- Known brain metastases, unless they have undergone definitive therapy and are neurologically stable at the time of study entry
- Standard chemotherapy or radiation less than 2 weeks of starting BIBW 2992, or experimental systemic cancer therapy less then 4 weeks of starting BIBW 2992. Note that prior palliative radiation to bony disease, CNS disease, or a limited thoracic area is allowed if there is measurable or progressive disease outside the field of radiation.
- Another malignancy within the last 3 years (except for non-melanoma skin cancer or a non-invasive/in situ cancer)
- Known pre-existing and clinically active interstitial lung disease
- Significant gastrointestinal disorders with diarrhea as a major symptom
- History of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia, or myocardial infarction within 6 months
- Cardiac left ventricular function with resting ejection fraction <50%
- Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug
- Pregnancy or breast feeding
- History of allergic reactions attributed to compounds of similar chemical or biologic composition of BIBW 2992
- Life expectancy of < 12 weeks
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:单组作业
- 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:BIBW 2992
BIBW 2992 Taken orally once a day
|
Taken orally once a day
其他名称:
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
|---|---|
|
Number of Participants That Have a T790M Mutation on Their Progression Biopsy.
大体时间:At the time of disease progression (median duration of 11.4 months from start of treatment)
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At the time of disease progression (median duration of 11.4 months from start of treatment)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Response Rate
大体时间:Baseline and then after the end of every two 28 day cycles until treatment is discontinued; median duration of followup of 19.3 months
|
The number of participants with either a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
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Baseline and then after the end of every two 28 day cycles until treatment is discontinued; median duration of followup of 19.3 months
|
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Median Progression-free and Overall Survival
大体时间:start of treatment, at the time of disease progression, time of death
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The progression-free and overall survival times.
Overall survival is measured from the start of treatment until the time of death or until the participant is lost to follow-up.
Progression free survival is measured from the start of treatment until the time of progression, death, or until the participant is lost to follow-up (whichever occurs first).
Progression is defined as having at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study with at least a 5 mm absolute increase in the sum of all lesions.
The appearance of one or more new lesions denotes disease progression.
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start of treatment, at the time of disease progression, time of death
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Number of Participants With Biopsy Complications From Repeat Tumor Biopsies
大体时间:7 days post biopsy and ≥ 30 days post-biopsy
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The number of participants with biopsy complications from repeat tumor biopsies taken following disease progression.
Biopsy complications are any adverse events considered to be potentially related to the biopsy.
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7 days post biopsy and ≥ 30 days post-biopsy
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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。
调查人员
- 首席研究员:Lecia V. Sequist, MD, PhD、Massachusetts General Hospital
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
2011年2月1日
初级完成 (实际的)
2017年3月1日
研究完成 (实际的)
2017年3月1日
研究注册日期
首次提交
2010年2月22日
首先提交符合 QC 标准的
2010年2月22日
首次发布 (估计)
2010年2月24日
研究记录更新
最后更新发布 (实际的)
2018年3月9日
上次提交的符合 QC 标准的更新
2018年3月5日
最后验证
2018年3月1日
更多信息
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.