Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib in Cancer Patients (CLEARSUN)
2012年7月11日 更新者：Heinz-Josef Klumpen、Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib (Sutent, SU11248) in Patients With Cancer
Sunitinib is an anticancer drug, but like most drugs, the effect varies from person to person.
This is partly due to a variation in how well each person eradicates the drug from the body.
This can lead to toxicity if the drug is eliminated slowly.
Just as important is inadvertent underdosing in people who eliminate the drug quickly which may lead to a reduced anti-cancer effect.
The investigators group has developed a battery of tests that may measure how an individual clears a drug from their body.
The investigators intend to apply these tests to a group of patients taking sunitinib to see whether any test will help predict the level of sunitinib in the body and also the side effects.
If a test seems to be promising from this study it may be possible to do a simple test on patients before they receive sunitinib so the best dose is chosen.
The tests involve identifying the genes that are involved with drug elimination (CYP3A, ABCB1, ABCG2, OCT1, OATP) as well as directly measuring elimination using marker drugs (midazolam clearance and sestamibi liver clearance).
研究概览
地位
完全的
条件
研究类型
观察性的
注册 (实际的)
52
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
取样方法
概率样本
研究人群
Patients with a malignancy treated with sunitinib
描述
Inclusion Criteria:
- Age >18
- A malignancy treated with single agent sunitinib
- ECOG 0, 1 or 2 at time of study accruement
- Any stable dose of therapy with sunitinib (defined as no dose change within 3 weeks prior to blood collection for pharmacokinetics)
- Adequate liver and renal function defined as serum bilirubin concentration less than 2 x ULN, AST and ALT less than 2.5 x ULN, serum creatinine concentration less than 2 x ULN
- No known primary liver disease and no other severe or uncontrolled concurrent medical condition within the first 3 months of treatment with sunitinib.
- Patients who have participated on other clinical studies of sunitinib will be suitable for this study.
- Signed informed consent
- Patients must not have Class ¾ cardiac problems as defined by the New York Heart Association criteria or any other severe or uncontrolled concurrent medical disease.
- Patients must not be pregnant or nursing and must be using an effective contraception method
Exclusion Criteria:
- Patients who are unable to sign informed consent
- Patients unable to give blood
- Patients with known midazolam allergies will not be included
- Patients must not be pregnant or nursing and must be using an effective contraception method
- Patients who had a bone-marrow-transplantation prior to sunitinib treatment
- Patients must not be taking routine systemic corticoid therapy
- Patients must not be taking therapeutic warfarin or warfarin derivates doses as anticoagulation at the time of study tests with an at least 2 weeks warfarin free period of time prior. Patients requiring anticoagulation may use low-molecular weight heparin
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
队列和干预
团体/队列 |
|---|
|
Sunitinib
Patients with a malignancy treated with sunitinib
|
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 |
|---|---|---|
|
To observe the correlation between ABCB1 polymorphisms in Exons 13, 22 and 27 and the clearance of sunitinib at steady state.
大体时间：4 weeks
|
A blood sample will be drawn on day 1 of any treatment cycle and at steady state of the same cycle (between Day 21 and 28 inclusive)
|
4 weeks
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
To determine whether ABCB1 genotype correlates with toxicity-adjusted dose of sunitinib
大体时间：3 months
|
Toxicity adjustments will be collected within the first 3 months and correlated with the ABCB1 genotypes.
|
3 months
|
|
To determine the pharmacokinetics at steady state of the sunitinib treatment.
大体时间：4 weeks
|
A blood sample will be drawn on day 1 of treatment cycle and at steady state of the same cycle (between Day 21 and 28 inclusive).
The time of the blood collection are at day1 and in the 4th week: pre-drug administration then at 4 hours, 8 hours and 24 hours after drug intake.
|
4 weeks
|
|
To examine correlations between ABCB1 genotype and toxicity grade according to CTC criteria.
大体时间：3 months
|
The toxicity data of the first 3 months of treatment will be collected.
|
3 months
|
|
To examine the correlation between genotype haplotype of other drug elimination genes, such as organic anion transporter proteins (OATP) and other biliary efflux proteins such as MRP2, BCRP with sunitinib clearance and toxicity adjusted dose.
大体时间：3 months
|
Investigations of drugelimination and clearance taken with in the first 4 weeks of the study will be collected as well as the toxicity data and dose adjustments within the first 3 month of treatment.
|
3 months
|
|
Correlation of drug elimination phenotype test (sestamibi liver scan and Midazolam clearance) with sunitinib clearance
大体时间：4 weeks
|
sestamibi liver scan and midazolam clearance test will be performed pre-treatment and at steady state (sometime between day 21-28)of study participation.
|
4 weeks
|
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。
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1月1日
初级完成 (实际的)
2011年6月1日
研究完成 (实际的)
2011年12月1日
研究注册日期
首次提交
2010年3月16日
首先提交符合 QC 标准的
2010年4月2日
首次发布 (估计)
2010年4月5日
研究记录更新
最后更新发布 (估计)
2012年7月12日
上次提交的符合 QC 标准的更新
2012年7月11日
最后验证
2012年7月1日
更多信息
与本研究相关的术语
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