Role of Gene Variation in Effectiveness of Gleevec Treatment

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT00342056

Enrollment

100

Registered

2006-06-21

Start date

2005-01-31

Completion date

2008-10-31

Last updated

2011-05-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer, Cancer

Keywords

Pharmacogenetics, Transporter Proteins, Drug Exposure, Imatinib, Retrospective, Cancer

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.

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.

Interventions

None listed

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion 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.

Countries

Belgium, United States

Outcome results