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

This study has been completed.
Sponsor:
Collaborators:
Erasmus Medical Center
South West Sydney Local Health District
Information provided by (Responsible Party):
Heinz-Josef Klumpen, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01098903
First received: March 16, 2010
Last updated: July 11, 2012
Last verified: July 2012
  Purpose

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).


Condition
Cancer

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib (Sutent, SU11248) in Patients With Cancer

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • To determine whether ABCB1 genotype correlates with toxicity-adjusted dose of sunitinib [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Toxicity adjustments will be collected within the first 3 months and correlated with the ABCB1 genotypes.

  • To determine the pharmacokinetics at steady state of the sunitinib treatment. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.

  • To examine correlations between ABCB1 genotype and toxicity grade according to CTC criteria. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    The toxicity data of the first 3 months of treatment will be collected.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Correlation of drug elimination phenotype test (sestamibi liver scan and Midazolam clearance) with sunitinib clearance [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    sestamibi liver scan and midazolam clearance test will be performed pre-treatment and at steady state (sometime between day 21-28)of study participation.


Enrollment: 52
Study Start Date: January 2009
Study Completion Date: December 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
Sunitinib
Patients with a malignancy treated with sunitinib

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients with a malignancy treated with sunitinib

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01098903

Locations
Australia, New South Wales
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Netherlands
Academic medical center Amsterdam
Amsterdam, Netherlands, 1105AZ
Erasmus Medical Center, Daniel Den Hoed Cancer Center
Rotterdam, Netherlands, 3075EA
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Erasmus Medical Center
South West Sydney Local Health District
  More Information

No publications provided

Responsible Party: Heinz-Josef Klumpen, md, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01098903     History of Changes
Other Study ID Numbers: HGWH0008
Study First Received: March 16, 2010
Last Updated: July 11, 2012
Health Authority: Australia: National Health and Medical Research Council

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
sunitinib
cancer
pharmacogenomics
pharmacokinetics
Patients who have a malignancy and are going to be treated with sunitinib
doseindividualism

Additional relevant MeSH terms:
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014