CancerCLEARSUNNCT01098903
Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib in Cancer Patients
An observational study of Cancer, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 3 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- How many people
- 52 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Jan 2009to Dec 2011
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with a malignancy treated with sunitinib
Who may be able to join
- 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.
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- 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
Who cannot join
- 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 locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Netherlands2 sites
Academic medical center Amsterdam
Amsterdam, 1105AZ
Erasmus Medical Center, Daniel Den Hoed Cancer Center
Rotterdam, 3075EA
About this study
Official title: Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib (Sutent, SU11248) in Patients With Cancer
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).
- Conditions
- Cancer
- Keywords
- sunitinib, cancer, pharmacogenomics, pharmacokinetics, Patients who have a malignancy and are going to be treated with sunitinib, doseindividualism
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib | Patients with a malignancy treated with sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 4 weeks
Secondary outcomes (5)
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.
Measured: 3 months
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.
Measured: 4 weeks
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.
Measured: 3 months
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.
Measured: 3 months
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.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2010 (estimated)
- Study startJan 2009
- Primary completionJun 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center, South West Sydney Local Health District
- Responsible party
- Principal investigator, Heinz-Josef Klumpen, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01098903
- Sponsor's protocol ID
- HGWH0008
- Acronym
- CLEARSUN
- Status last verified
- Jul 2012
- First submitted
- 16 Mar 2010
- Last updated
- 12 Jul 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib (Sutent, SU11248) in Patients With Cancer
- ClinicalTrials.gov ID
- NCT01098903
- Acronym / sponsor ID
- CLEARSUN / HGWH0008
- Conditions
- Cancer
- Keywords
- sunitinib, cancer, pharmacogenomics, pharmacokinetics, Patients who have a malignancy and are going to be treated with sunitinib, doseindividualism
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- Erasmus Medical Center, South West Sydney Local Health District
- Study start
- Jan 2009
- Primary completion
- Jun 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 5 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sunitinib | – | –Patients with a malignancy treated with sunitinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a malignancy treated with sunitinib
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To observe the correlation between ABCB1 polymorphisms in Exons 13, 22 and 27 and the clearance of sunitinib at steady state.
Time frame: 4 weeks
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)
5 secondary outcomes
To determine whether ABCB1 genotype correlates with toxicity-adjusted dose of sunitinib
Time frame: 3 months
To determine the pharmacokinetics at steady state of the sunitinib treatment.
Time frame: 4 weeks
To examine correlations between ABCB1 genotype and toxicity grade according to CTC criteria.
Time frame: 3 months
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.
Time frame: 3 months
Correlation of drug elimination phenotype test (sestamibi liver scan and Midazolam clearance) with sunitinib clearance
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cancer, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To observe the correlation between ABCB1 polymorphisms in Exons 13, 22 and 27 and the clearance of sunitinib at steady state. (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2012.