PTK787 + Trastuzumab for HER2 Overexpressing Metastatic Breast Cancer
2015年12月8日 更新者：Kathy Miller, MD、Hoosier Cancer Research Network
A Phase I/II Study of PTK787 in Combination With Trastuzumab in Patients With Newly Diagnosed HER2 Overexpressing Locally Recurrent or Metastatic Breast Cancer: Hoosier Oncology Group Trial BRE04-80
HER2 gene amplification increases VEGF production in breast cancers; combined inhibition of HER2 and VEGF enhances response in xenograft models. The upregulation of VEGF in HER2-overexpressing breast cancers may contribute to the aggressive phenotype observed in HER2-positive breast cancer. New therapeutics targeting VEGF and/or its receptors may enhance the efficacy of trastuzumab monotherapy.
This trial will investigate the safety and efficacy of combined HER2 and VEGF inhibition.
研究概览
详细说明
OUTLINE: This is a multi-center study.
PTK787 daily plus trastuzumab 4 mg/kg IV week 1, followed by 2 mg/kg weekly with disease evaluation every other cycle.
Patients may continue treatment until disease progression or toxicity intervenes.
Performance Status: ECOG 0 or 1
Life Expectancy: Not specified
Hematopoietic:
- ANC > 1500 mm3
- Platelets > 100,000 mm3
- Hemoglobin > 9 g/dL
- PTT and INR < 1.5 x ULN
Hepatic:
- ALT and AST < 3 x ULN (< 5 x ULN in patients with known liver metastases)
- Alkaline phosphatase < 2.5 x ULN
- Serum bilirubin < 1.5 x ULN
Renal:
- Serum creatinine < 1.5 x ULN
- Proteinuria < 1+ by dipstick OR total urinary protein < 500 mg/24 hours with measured creatinine clearance (CrCl) ≥ 50 mL/min
Cardiovascular:
- No clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months.
- LVEF > LLN by MUGA or ECHO (obtained within 28 days prior to being registered for protocol therapy)
Pulmonary:
- Not specified
研究类型
介入性
注册 (实际的)
7
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
-
-
Indiana
-
Elkhart、Indiana、美国、46515
- Elkhart Clinic
-
Fort Wayne、Indiana、美国、46815
- Fort Wayne Oncology & Hematology, Inc
-
Goshen、Indiana、美国、46527
- Center for Cancer Care at Goshen Health System
-
Indianapolis、Indiana、美国、46202
- Indiana University Cancer Center
-
Lafayette、Indiana、美国、47904
- Arnett Cancer Care
-
Muncie、Indiana、美国、47303
- Medical Consultants, P.C.
-
South Bend、Indiana、美国、46601
- Northern Indiana Cancer Research Consortium
-
Terre Haute、Indiana、美国、47804
- AP&S Clinic
-
-
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
女性
描述
Inclusion Criteria:
- Histologic or cytologic diagnosis of breast cancer with evidence of measurable (1) unresectable, locally recurrent, or (2) metastatic disease. Locally recurrent disease must not be amenable to resection OR radiation with curative intent.
- Patient's disease may not involve more than 3 metastatic sites. In addition, patient may not be symptomatic from pulmonary metastasis or have liver metastasis involving > 50% of parenchyma.
- HER2 gene amplification by FISH. HER protein overexpression by immunohistochemistry will not be sufficient for entry.
- Negative pregnancy test
Exclusion Criteria:
- No prior cytotoxic chemotherapy or trastuzumab for locally recurrent or metastatic disease.
- No prior treatment with any VEGF inhibiting agents
- No history or presence of central nervous system (CNS) disease.
- No other forms of cancer therapy including radiation, chemotherapy and hormonal therapy within 21 days prior to being registered for protocol therapy.
- No major surgery within 28 days prior to being registered for protocol therapy.
- No uncontrolled hypertension (SBP > 170, DBP > 90), history of labile hypertension or history of poor compliance with antihypertensive therapy.
- No requirement for therapeutic anticoagulation, regular aspirin (> 325 mg/day) or NSAID use.
- No current breast feeding.
- No impairment of gastrointestinal (GI) function that may significantly alter the absorption of PTK787.
- No evidence of other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator).
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：Single Group Assignment
Trastuzumab + PTK787 for HER2 positive patients
|
PTK787 daily
Trastuzumab 4 mg/kg IV week 1, followed by 2 mg/kg weekly with disease evaluation every other cycle*
|
研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
|
Phase I Cohorts:
大体时间：18 months
|
18 months
|
|
The primary objective is to ensure the safety and tolerability of the combination of Trastuzumab and PTK787,
大体时间：18 months
|
18 months
|
|
Phase II Cohorts:
大体时间：18 months
|
18 months
|
|
To assess response rate of PTK787 combined with trastuzumab in patients with newly diagnosed HER2 overexpressing
大体时间：18 months
|
18 months
|
次要结果测量
结果测量 |
大体时间 |
|---|---|
|
Phase II Cohorts:
大体时间：12 months
|
12 months
|
|
To assess the safety and tolerability of PTK787 combined with trastuzumab
大体时间：12 months
|
12 months
|
|
To assess the time to progression and clinical benefit of PTK787 combined with trastuzumab
大体时间：12 months
|
12 months
|
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
2005年1月1日
初级完成 (实际的)
2006年8月1日
研究完成 (实际的)
2006年8月1日
研究注册日期
首次提交
2005年9月12日
首先提交符合 QC 标准的
2005年9月14日
首次发布 (估计)
2005年9月22日
研究记录更新
最后更新发布 (估计)
2015年12月9日
上次提交的符合 QC 标准的更新
2015年12月8日
最后验证
2015年12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.