Predictive value of drug elimination gene polymorphisms on clearance and dose adjustment of sunitinib (Sutent, SU11248) in patients with cancer

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 10

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 3/4 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

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary study parameters:<br /><br>The correlation between ABCB1 polymorphisms in Exons 13, 22 and 27 and the<br /><br>clearance of sunitinib at steady state </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary study parameters:<br /><br>- The correlation between ABCB1 genotype and toxicity-adjusted dose of<br /><br>sunitinib<br /><br><br /><br>- The pharmacokinetics at steady state of the sunitinib treatment<br /><br>- The correlations between ABCB1 genotype and toxicity grade according to CTC<br /><br>criteria<br /><br>- The correlation between genotype haplotype of other drug elimination genes,<br /><br>such as organic anion transporter proteins (OATP) and other biliary efflux<br /><br>proteins such as MRP2, BCRP with sunitinib clearance and toxicity adjusted<br /><br>dose<br /><br>- The correlation of drug elimination phenotype test (sestamibi liver scan and<br /><br>Midazolam clearance) with sunitinib clearance</p><br>