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

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Status: Completed

Conditions: Cancer

Study type: Observational

Funder types: Other

Identifiers

NCT01098903

HGWH0008

Details and patient eligibility

About

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).

Enrollment: 52 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

52 participants in 1 patient group

Sunitinib

Description:

Patients with a malignancy treated with sunitinib