Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib (Sutent, SU11248) in Patients With Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 3
- 主要终点
- To observe the correlation between ABCB1 polymorphisms in Exons 13, 22 and 27 and the clearance of sunitinib at steady state.
研究概览
简要总结
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).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
To observe the correlation between ABCB1 polymorphisms in Exons 13, 22 and 27 and the clearance of sunitinib at steady state.
时间窗: 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)
次要结局
- To determine whether ABCB1 genotype correlates with toxicity-adjusted dose of sunitinib(3 months)
- To determine the pharmacokinetics at steady state of the sunitinib treatment.(4 weeks)
- To examine correlations between ABCB1 genotype and toxicity grade according to CTC criteria.(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.(3 months)
- Correlation of drug elimination phenotype test (sestamibi liver scan and Midazolam clearance) with sunitinib clearance(4 weeks)
研究者
Heinz-Josef Klumpen
md
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)