The main group are patients with renal cell cancer currently being or about to be treated with sunitinib. Other diseases with efficacy of sunitinib are Gastro Intestinal Stromal cell tumour (GIST).
Conditions
Sponsors
Academic Medical Centre
Eligibility
Sex/Gender
All
Inclusion 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To observe the correlation between ABCB1 polymorphisms in Exons 13, 22 and 27 and the clearance of sunitinib at steady state. ;Secondary Objective: • To determine whether ABCB1 genotype correlates with toxicity-adjusted dose of sunitinib • To determine the pharmacokinetics at steady state of the sunitinib treatment. • To examine correlations between ABCB1 genotype and toxicity grade according to CTC criteria. • 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. • Correlation of drug elimination phenotype test (sestamibi liver scan and Midazolam clearance) with sunitinib clearance;Primary end point(s): The endpoint of the study is a correlation between sunitinib clearance and toxicityadjusted dose with ABCB1 genotype examining SNPs in exons 13, 22,and 27 as well as haplotypes of these exons. | — |
Countries
Netherlands
Outcome results
None listed