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

NCT01098903 | Completed

• 1 other identifier: HGWH0008
• Study Type: observational
• Target: 52
• Locations: 2 countries
• Sites: 3

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).

Conditions

Cancer

Keywords

sunitinib; cancer; pharmacogenomics; pharmacokinetics; Patients who have a malignancy and are going to be treated with sunitinib; doseindividualism

Outcome Measures

Primary Outcomes (1)

• 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)

  4 weeks

Secondary Outcomes (5)

• To determine whether ABCB1 genotype correlates with toxicity-adjusted dose of sunitinib

  3 months

• To determine the pharmacokinetics at steady state of the sunitinib treatment.

  4 weeks

• To examine correlations between ABCB1 genotype and toxicity grade according to CTC criteria.

  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.

  3 months

• Correlation of drug elimination phenotype test (sestamibi liver scan and Midazolam clearance) with sunitinib clearance

  4 weeks

Study Arms (1)

Sunitinib

Patients with a malignancy treated with sunitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with a malignancy treated with sunitinib

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Erasmus Medical Center: collaborator
• South West Sydney Local Health District: collaborator

Study Sites (3)

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Academic medical center Amsterdam

Amsterdam, 1105AZ, Netherlands

Location

Erasmus Medical Center, Daniel Den Hoed Cancer Center

Rotterdam, 3075EA, Netherlands

Location

MeSH Terms

Conditions

Neoplasms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: md

Study Record Dates

• First Submitted: March 16, 2010
• First Posted: April 5, 2010
• Study Start: January 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: December 1, 2011
• Last Updated: July 12, 2012

Record last verified: 2012-07

Locations

AU (1); NL (2)