Clinical trial NCT01098903: Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib in Cancer Patients
Official title: Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib (Sutent, SU11248) in Patients With Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cancer
Keywords: sunitinib
cancer
pharmacogenomics
pharmacokinetics
Patients who have a malignancy and are going to be treated with sunitinib
doseindividualism
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
name: South West Sydney Local Health District
First posted: 2010-04-05
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with a malignancy treated with sunitinib

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: To observe the correlation between ABCB1 polymorphisms in Exons 13, 22 and 27 and the clearance of sunitinib at steady state.
timeFrame: 4 weeks
Secondary outcomes:
measure: To determine whether ABCB1 genotype correlates with toxicity-adjusted dose of sunitinib
timeFrame: 3 months
measure: To determine the pharmacokinetics at steady state of the sunitinib treatment.
timeFrame: 4 weeks
measure: To examine correlations between ABCB1 genotype and toxicity grade according to CTC criteria.
timeFrame: 3 months
measure: 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.
timeFrame: 3 months
measure: Correlation of drug elimination phenotype test (sestamibi liver scan and Midazolam clearance) with sunitinib clearance
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Amsterdam
country: Netherlands
facility: Academic medical center Amsterdam
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center, Daniel Den Hoed Cancer Center
Study officials:
References: