Role of Gene Variation in Effectiveness of Gleevec Treatment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00342056
Recruitment Status : Completed
First Posted : June 21, 2006
Last Update Posted : May 25, 2011
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

This study will examine DNA from cancer patients previously treated with Gleevec to look for a variation (mutation) of the ABCG2 gene that may render the drug less effective in certain patients. Gleevec is used to treat chronic myeloid leukemia and gastrointestinal tumors. Although most patients respond to treatment, many with advanced disease develop resistance to the drug. It is thought that in some patients this resistance results from the action of a protein that causes Gleevec to be pumped out of the cells, reducing its usefulness.

Patients enrolled in clinical trials of Gleevec at the National Cancer Institute and at other participating institutions are eligible for this study.

DNA from patients' blood samples are analyzed for the ABCG2 gene and correlated with clinical data, such as the patient's age, race, disease state, weight, height, and body surface area. It will also look at the drug dose, how often the drug is given, the duration of treatment, side effects and other medications taken.

Condition or disease
Cancer Breast Cancer

Detailed Description:
ABCG2, also known as breast cancer resistance protein (BCRP), is an ATP-binding cassette (ABC) transporter that has been shown to confer resistance to several drugs, including mitoxantrone and topotecan. Gleevec (imatinib mesylate) has recently been identified as a substrate for ABCG2. The expression of ABCG2 in the human jejunum has been shown to be higher than expression MDR1, which encodes for P-glycoprotein. Therefore, it is plausible that the oral bioavailability of Gleevec could be dependent on the extent of transport. A single nucleotide polymorphism (C421A) has been identified in ABCG2 and has been shown in vitro to result in functional inactivation of this transporter protein. In this study, the relationship between the genotypes of ABCG2 and the pharmacokinetics or side effects will be retrospectively explored in patients with cancer who had been previously enrolled on clinical trials of Gleevec.

Study Type : Observational
Enrollment : 100 participants
Official Title: Analysis of ABCG2 Genotype in Gleevec Treated Cancer Patients to Assess the Association of a Single Nucleotide Polymorphism (C421A) in ABCG2 and Response to Treatment
Study Start Date : January 2005
Actual Study Completion Date : October 2008

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

In this retrospective study, all cancer patients enrolled on IRB approved clinical trials of Gleevec from both the National Cancer and outside institutions will be eligible, provided that they have consented in the original consent form.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00342056

United States, District of Columbia
Washington Hospital Center
Washington, District of Columbia, United States, 20010
Katholieke Universiteit Leuven, U Hospitals UZ Gasthuisberg
Leuven, Belgium
Sponsors and Collaborators
National Cancer Institute (NCI)

Publications: Identifier: NCT00342056     History of Changes
Obsolete Identifiers: NCT00897000
Other Study ID Numbers: 999905090
First Posted: June 21, 2006    Key Record Dates
Last Update Posted: May 25, 2011
Last Verified: May 2011

Keywords provided by National Institutes of Health Clinical Center (CC):
Transporter Proteins
Drug Exposure

Additional relevant MeSH terms:
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action