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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01098903




Registration number
NCT01098903
Ethics application status
Date submitted
16/03/2010
Date registered
5/04/2010
Date last updated
12/07/2012

Titles & IDs
Public title
Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib in Cancer Patients
Scientific title
Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib (Sutent, SU11248) in Patients With Cancer
Secondary ID [1] 0 0
HGWH0008
Universal Trial Number (UTN)
Trial acronym
CLEARSUN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Sunitinib - Patients with a malignancy treated with sunitinib

Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
4 weeks
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
3 months
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
4 weeks
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
3 months
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
3 months
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
4 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose
Duration
Selection
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
Netherlands
State/province [1] 0 0
Amsterdam
Country [2] 0 0
Netherlands
State/province [2] 0 0
Rotterdam

Funding & Sponsors
Primary sponsor type
Other
Name
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Erasmus Medical Center
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
South West Sydney Local Health District
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT01098903
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications