Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib in Cancer Patients

Cancer Clinical Trial

— CLEARSUN  

Official title:

Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib (Sutent, SU11248) in Patients With Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01098903
• Other study ID #: HGWH0008
• Status: Completed
• Phase: N/A
• First received: March 16, 2010
• Last updated: July 11, 2012
• Start date: January 2009
• Est. completion date: December 2011

Study information

• Verified date: July 2012
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: National Health and Medical Research Council
• Study type: Observational

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: December 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Cancer

Locations

Country	Name	City	State
Australia	Westmead Hospital	Westmead	New South Wales
Netherlands	Academic medical center Amsterdam	Amsterdam
Netherlands	Erasmus Medical Center, Daniel Den Hoed Cancer Center	Rotterdam

Sponsors (3)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	Erasmus Medical Center, South West Sydney Local Health District

Countries where clinical trial is conducted

Australia,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To observe the correlation between ABCB1 polymorphisms in Exons 13, 22 and 27 and the clearance of sunitinib at steady state.	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	No
Secondary	To determine whether ABCB1 genotype correlates with toxicity-adjusted dose of sunitinib	Toxicity adjustments will be collected within the first 3 months and correlated with the ABCB1 genotypes.	3 months	No
Secondary	To determine the pharmacokinetics at steady state of the sunitinib treatment.	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	No
Secondary	To examine correlations between ABCB1 genotype and toxicity grade according to CTC criteria.	The toxicity data of the first 3 months of treatment will be collected.	3 months	No
Secondary	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.	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	No
Secondary	Correlation of drug elimination phenotype test (sestamibi liver scan and Midazolam clearance) with sunitinib clearance	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	No