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Role of Gene Variation in Effectiveness of Gleevec Treatment

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00342056
First received: June 19, 2006
Last updated: May 24, 2011
Last verified: May 2011
  Purpose

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
Cancer
Breast Cancer

Study Type: Observational
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 100
Study Start Date: January 2005
Study Completion Date: October 2008
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

Not applicable.

  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: NCT00342056

Locations
United States, District of Columbia
Washington Hospital Center
Washington, District of Columbia, United States, 20010
Belgium
Katholieke Universiteit Leuven, U Hospitals UZ Gasthuisberg
Leuven, Belgium
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00342056     History of Changes
Obsolete Identifiers: NCT00897000
Other Study ID Numbers: 999905090, 05-C-N090
Study First Received: June 19, 2006
Last Updated: May 24, 2011
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on November 20, 2014