Role of Gene Variation in Effectiveness of Gleevec Treatment

NCT ID: NCT00342056

Last Updated: 2011-05-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2008-10-31

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.

Conditions

Cancer; Breast Cancer

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Locations

Washington Hospital Center

Washington D.C., District of Columbia, United States

Katholieke Universiteit Leuven, U Hospitals UZ Gasthuisberg

Leuven, , Belgium

Countries

United States; Belgium

References

Bailey-Dell KJ, Hassel B, Doyle LA, Ross DD. Promoter characterization and genomic organization of the human breast cancer resistance protein (ATP-binding cassette transporter G2) gene. Biochim Biophys Acta. 2001 Sep 21;1520(3):234-41. doi: 10.1016/s0167-4781(01)00270-6.

Reference Type: BACKGROUND

PMID: 11566359 (View on PubMed)

Bates SE, Robey R, Miyake K, Rao K, Ross DD, Litman T. The role of half-transporters in multidrug resistance. J Bioenerg Biomembr. 2001 Dec;33(6):503-11. doi: 10.1023/a:1012879205914.

Reference Type: BACKGROUND

PMID: 11804192 (View on PubMed)

Leonard GD, Polgar O, Bates SE. ABC transporters and inhibitors: new targets, new agents. Curr Opin Investig Drugs. 2002 Nov;3(11):1652-9.

Reference Type: BACKGROUND

PMID: 12476969 (View on PubMed)

Other Identifiers

05-C-N090

Identifier Type: -

Identifier Source: secondary_id

999905090

Identifier Type: -

Identifier Source: org_study_id

NCT00897000

Identifier Type: -

Identifier Source: nct_alias