Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib in Cancer Patients (CLEARSUN)
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).
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib (Sutent, SU11248) in Patients With Cancer|
- To observe the correlation between ABCB1 polymorphisms in Exons 13, 22 and 27 and the clearance of sunitinib at steady state. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]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)
- To determine whether ABCB1 genotype correlates with toxicity-adjusted dose of sunitinib [ Time Frame: 3 months ] [ Designated as safety issue: No ]Toxicity adjustments will be collected within the first 3 months and correlated with the ABCB1 genotypes.
- To determine the pharmacokinetics at steady state of the sunitinib treatment. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]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.
- To examine correlations between ABCB1 genotype and toxicity grade according to CTC criteria. [ Time Frame: 3 months ] [ Designated as safety issue: No ]The toxicity data of the first 3 months of treatment will be collected.
- 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. [ Time Frame: 3 months ] [ Designated as safety issue: No ]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.
- Correlation of drug elimination phenotype test (sestamibi liver scan and Midazolam clearance) with sunitinib clearance [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]sestamibi liver scan and midazolam clearance test will be performed pre-treatment and at steady state (sometime between day 21-28)of study participation.
|Study Start Date:||January 2009|
|Study Completion Date:||December 2011|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
Patients with a malignancy treated with sunitinib
Please refer to this study by its ClinicalTrials.gov identifier: NCT01098903
|Australia, New South Wales|
|Westmead, New South Wales, Australia, 2145|
|Academic medical center Amsterdam|
|Amsterdam, Netherlands, 1105AZ|
|Erasmus Medical Center, Daniel Den Hoed Cancer Center|
|Rotterdam, Netherlands, 3075EA|