A Study of the Combination of Erlotinib and Pertuzumab in Patients With Relapsed Non-small Cell Lung Cancer (PENGUIN)
2013年5月14日 更新者：Genentech, Inc.
An Open-label Phase II Multicenter Study of the Safety and Activity (as Measured by FDG-PET Imaging Changes) of the Combination of Erlotinib and Pertuzumab in Patients With Relapsed Non-small Cell Lung Cancer
This was a Phase II, open-label, single-arm, single-stage, multicenter trial in patients with relapsed non-small cell lung cancer (NSCLC), with the objective of assessing the activity of the combination of erlotinib and pertuzumab on the basis of the endpoint of FDG-PET response rate.
研究概览
研究类型
介入性
注册 (实际的)
41
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。
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:
- Histologically confirmed non-small cell lung cancer (NSCLC).
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
- Recurrent or progressive disease after receiving at least 1, but no more than two, chemotherapy regimens for advanced or metastatic NSCLC.
- Recovery from reversible acute effects of prior anti-cancer therapy (chemotherapy, radiotherapy, or investigational treatment) to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade ≤ 1 (excluding alopecia).
- Ability to comply with the study and follow-up procedures, including all specified imaging studies.
- Ability to take oral medication.
- Life expectancy ≥ 3 months.
- Measurable disease on computed tomography (CT).
- At least 1 extracerebral lesion on 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography (FDG-PET) scan that is suitable for response assessment, that is measurable, and ≥ 15 mm on CT.
- Left ventricular ejection fraction (LVEF) ≥ 50%, as determined by echocardiogram or MUltiple Gated Acquisition (MUGA) scan.
- For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the patient and/or partner.
- Availability and willingness to provide sufficient tumor tissue for testing for epidermal growth factor receptor (EGFR) mutations, and other human epidermal growth factor receptor (HER) pathway and NSCLC-related biomarkers.
Exclusion Criteria:
- Prior treatment with an investigational or marketed agent for the purpose of inhibiting HER family members (including HER1, HER2, HER3, and HER4). This includes, but is not limited to erlotinib, gefitinib, pertuzumab, cetuximab, and panitumumab.
- Chemotherapy, radiotherapy, or investigational treatment within 28 days of start of study (ie, prior to Day 0) or from which patients have not yet recovered.
- Inability to take oral medications, disease affecting gastrointestinal absorption, or prior surgical procedure affecting gastrointestinal absorption.
- Uncontrolled diabetes.
- Clinical or radiographic evidence of new or progression of pre-existing central nervous system (CNS) metastases.
- Current severe, uncontrolled systemic disease (eg, clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders; ulcers; or bone fractures).
- Current uncontrolled hypertension or unstable angina.
- History of congestive heart failure (CHF) of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia).
- History of myocardial infarction within 6 months of enrollment or history of unstable angina.
- Any evidence of an unstable infection as suggested by an infectious process, coupled with hypotension and/or tachycardia and/or fever and/or positive blood culture.
- Known human immunodeficiency virus (HIV) infection.
- Uncontrolled hypercalcemia.
- Pregnancy or lactation.
- History of another malignancy in the past 2 years, unless the malignancy has been adequately treated, is currently not detectable, and is associated with a 5-year survival > 90%.
- Claustrophobia.
- Any other disease, condition, physical examination finding, or clinical laboratory finding that, in the opinion of the investigator, makes the patient inappropriate for the study.
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：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：Pertuzumab + erlotinib
Patients received pertuzumab 840 mg intravenously (IV) 1 time (loading dose) followed by 420 mg IV (maintenance dose) every 3 weeks (q3w) plus erlotinib 150 mg orally once a day which was reduced to 100 mg orally once a day in a protocol amendment dated 19 May 2010.
|
After a single administration of a loading dose of 840 mg IV, patients received a maintenance dose of 420 mg IV every 3 weeks (q3w).
其他名称：
Patients received 150 mg orally once a day which was reduced to 100 mg orally once a day in a protocol amendment dated 19 May 2010.
其他名称：
|
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 |
|---|---|---|
|
Percentage of Patients With a 2-deoxy-2-[18F]Fluoro-D-glucose-positron Emission Tomography (FDG-PET) Response at Day 56 in All Patients and in Epidermal Growth Factor Receptor (EGFR) Mutant and Wild-type Subgroups
大体时间：Baseline to Day 56
|
The assessment of FDG-PET response was performed by a central reading site.
PET response was based on the maximum standard uptake value (SUVmax) of up to 5 regions of interest (ROI).
The tumor ROIs were identified for each patient on pretreatment FDG-PET scans and corresponded to a subset of the target lesions identified for Response Evaluation Criteria for Solid Tumors (RECIST) analysis.
Specifically, the SUVmax of each ROI on the on-treatment scans was compared with the SUVmax on the corresponding pretreatment scan and the percent change was calculated.
When there was more than 1 ROI, the overall percent change in SUVmax was the arithmetic mean of the percent changes in SUVmax for each of the ROIs (mSUVmax).
An PET response is defined as a decrease of ≥ 20% in mSUVmax.
EGFR mutation status was assessed in tumor tissue samples taken from each patient.
|
Baseline to Day 56
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Progression-free Survival (PFS)
大体时间：Baseline to the end of the study (up to 3 years)
|
PFS was defined as the time from the first dosing with pertuzumab and erlotinib to the first occurrence of disease progression (PD), as determined by the investigator and based on computed tomography using Response Evaluation Criteria in Solid Tumors (RECIST), or death from any cause, whichever comes first.
PD was defined as ≥ 20% increase in the sum of the longest diameter of target lesions (TL), taking as reference the smallest sum longest diameter recorded since treatment started, the unequivocal progression of existing non-target lesions (non-TL), or the appearance of 1 or more new lesions.
TLs were selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically.
All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, were identified as TLs.
All other lesions (or sites of disease) were identified as non-TLs.
|
Baseline to the end of the study (up to 3 years)
|
|
Overall Survival (OS)
大体时间：Baseline to the end of the study (up to 3 years)
|
Overall survival was defined as the time from the date of first dosing with pertuzumab and erlotinib until the date of patient death from any cause.
|
Baseline to the end of the study (up to 3 years)
|
|
Percentage of Patients With an Objective Response (OR)
大体时间：Baseline to the end of the study (up to 3 years)
|
OR was defined as a complete response (CR) or a partial response (PR) as determined by the investigator and based on computed tomography (CT) using Response Evaluation Criteria in Solid Tumors (RECIST) on 2 consecutive occasions at least 4 weeks apart.
A complete response was defined as the disappearance of all target and non-target lesions and normalization of tumor marker level.
A partial response was defined as ≥ 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, or the persistence of 1 or more non-target lesions and/or the maintenance of a tumor marker level above the normal limits.
|
Baseline to the end of the study (up to 3 years)
|
|
Percentage of Patients With Disease Control (DC) at Day 56
大体时间：Baseline to Day 56
|
DC was defined as a CR, a PR, or stable disease (SD) as determined by the investigator and based on CT using RECIST.
A CR was defined as the disappearance of all target (TL) and non-target lesions (nTL).
A PR was defined as ≥ 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline sum longest diameter, or the persistence of 1 or more nTLs and/or maintenance of a tumor marker level (TML) above normal limits.
For TLs, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter (SSLD) since treatment started.
For nTLs, SD was defined as the persistence of 1 or more lesions and/or maintenance of a TML above normal limits.
PD was defined as ≥ 20% increase in the SLD of TLs, taking as reference the SSLD recorded since treatment started, the appearance of 1 or more new lesions, or the unequivocal progression of existing nTLs.
|
Baseline to Day 56
|
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。
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
2009年3月1日
初级完成 (实际的)
2012年3月1日
研究完成 (实际的)
2012年3月1日
研究注册日期
首次提交
2009年3月4日
首先提交符合 QC 标准的
2009年3月4日
首次发布 (估计)
2009年3月5日
研究记录更新
最后更新发布 (估计)
2013年5月21日
上次提交的符合 QC 标准的更新
2013年5月14日
最后验证
2013年5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.