Lapatinib and Bortezomib in Patients With Advanced Malignancies
A Phase I Study of the HER1, HER2 Dual Kinase Inhibitor, Lapatinib Plus the Proteosomal Inhibitor Bortezomib in Patients With Advanced Malignancies
This study is for patients with an advanced type of cancer for which no curative treatment exists.
The purpose of this study is to test the safety and efficacy of the combination of the study drugs, lapatinib and bortezomib. Lapatinib is a drug that targets two proteins important for the growth of cancer cells known as HER1 (EGFR) and HER2. By inhibiting these proteins, lapatinib can inhibit cancer cell growth and even lead to their death. Lapatinib is an oral pill given by mouth once every day. Lapatinib is approved by the FDA for patients with breast cancer.
Bortezomib is a drug that targets a part of cancer cells known as the proteosome. By inhibiting the proteosome, bortezomib can inhibit cancer cell growth and even lead to their death. Bortezomib is given intravenously, once a week, 2 out of every 3 weeks. Bortezomib is approved by the FDA for patients with multiple myeloma and mantle cell lymphoma.
This research is being done because it is not known if the combination of lapatinib and bortezomib will work better than lapatinib or bortezomib alone, although in the lab and in animal studies the combination of the two drugs was much more effective than either drug alone.
As part of this study biopsies will be taken of patients' tumors before any treatment, after starting lapatinib alone, and after receiving both lapatinib and bortezomib. Investigators want to study what markers inside tumors may relate to how well these two medications work. These biopsies are required as part of the study.
研究概览
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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District of Columbia
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Washington、District of Columbia、美国、20007
- Georgetown Lombardi Comprehensive Cancer Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Histologically proven malignant solid tumor with measurable disease
- Progression on, or intolerance of, or ineligibility for all standard therapies
- Biopsy accessible tumor deposits
- LVEF >/= institutional normal
- Corrected QT interval less than 500 milliseconds by EKG
- ECOG performance status 0-2
- Subjects with no brain metastases or a history of previously treated brain metastases who have been treated by surgery or stereotactic radiosurgery at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of active intercranial disease and have not had treatment with steroids within 1 week of enrollment.
- Adequate hepatic, bone marrow, and renal function
- Partial thromboplastin time must be </= 1.5 x upper limit of institution's normal range and INR < 1.5. Subjects on anticoagulants will be permitted to enroll as long as the INR is in the acceptable therapeutic range.
- Life expectancy > 12 weeks
- Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months.
- Subject is capable of understanding and complying with parameters as outlines in the protocol and able to sign and date the informed consent form.
Exclusion Criteria:
- Patients with lymphomas
- CNS metastases which do not meet the criteria outlines in the inclusion criteria
- Peripheral neuropathy >/= Grade 2 at baseline or peripheral neuropathy >/= Grade 1 with neuropathic pain
- Active severe infection or known chronic infection with HIV or hepatitis B virus
- Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 months
- Life-threatening visceral disease or other severe concurrent disease
- Women who are pregnant or breastfeeding
- Anticipated patient survival under 3 months
- Concurrent use of known CYP 3A4 inhibiting or activating medications
学习计划
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 |
|---|---|
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实验性的：Bortezomib plus lapatinib
Combination treatment with lapatinib and bortezomib
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Lapatinib will be taken orally continuously for 28 days of each 28-day cycle, including a run-in of lapatinib alone day -7 to day 1 of cycle 1. Bortezomib will be administered IV on days 1, 8, and 15 of each cycle. The exact doses of both drugs will be dependent on which cohort the subject is in and adverse events observed in previous cohorts.
其他名称：
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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 |
|---|---|---|
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Maximum tolerated dose
大体时间：18 months
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The highest dose at which </= 1 out of 6 subjects has a dose-limiting toxicity
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18 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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toxicity
大体时间：18 months
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Adverse events seen during the trial graded using CTCAE version 4
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18 months
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Response rate
大体时间：18 months
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complete response and partial response measured by RECIST 1.1
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18 months
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Disease control rate
大体时间：2 months
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stable disease after two cycles+ partial response + complete response as determined by RECIST 1.1 criteria
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2 months
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Pharmacodynamics
大体时间：pre-treatment, after 1 week of therapy and adter 3 weeks of therapy
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To assess changes in the following in serial tumor samples: EGFR, HER2, HER3, AKT, Actin, ERK, GSK3a-beta, IGF-1R, MEK 1/2, mTOR, p70S6, P13K, PTEN, SHC Y317, NFKB, IKB, CFK4, CDK2, cyclin D1, cyclin A, Cyclin E, p15, p16, p21, p27, beta-catenin, and ras gene mutation
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pre-treatment, after 1 week of therapy and adter 3 weeks of therapy
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合作者和调查者
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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