Tamoxifen Pharmacogenetics and Clinical Effects

NCT ID: NCT00228930

Last Updated: 2008-09-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

297 participants

Study Classification

OBSERVATIONAL

Study Start Date

2002-09-30

Study Completion Date

2007-08-31

Brief Summary

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The purpose of this research is to try to identify which women who take tamoxifen are likely to suffer from hot flashes or are more likely to have other side effects or benefits from the drug. The researchers will do so by determining whether there are mutations that normally occur in human DNA that might influence the way individuals respond to medications.

Detailed Description

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The study will test the following hypotheses.

1. There is a relationship between genetically distinct metabolic profiles of tamoxifen and the frequency and severity of hot flashes in women on chronic tamoxifen therapy.
2. Genetically distinct metabolic profiles for tamoxifen effect lipid profile, bone turnover metabolites and bone mineral density, and coagulation factors.
3. Different genetic profiles of estrogen responsive genes influence the pharmacodynamic effects of tamoxifen in cardiovascular system.

Conditions

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Breast Cancer

Keywords

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Breast Cancer Tamoxifen Prevention

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Tamoxifen (pharmacodynamic analysis)

Tamoxifen 20mg po daily

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. 18-years or older
2. Women with a prior breast cancer or who are at a high risk for developing the disease and about to start tamoxifen therapy.
3. Participants must not be treated with concomitant chemotherapy or hormone therapy other than tamoxifen. They must not have ovarian ablation or currently being treated with radiation therapy and/or chronic corticosteroids.
4. The participant must not be taking anti-hot flash therapy (clonidine, bellergal, megestrol acetate). Vitamin E, selective serotonin reuptake inhibitors, or herbal remedies are allowed provided that the participant has been taking the remedy for at least 4 weeks and intends to continue the remedy for at least the first month while on the study, and allows for one-month follow up evaluation (hot flash diaries and blood samples).
5. The participant must not be pregnant or lactating.
6. The participant is able and willing to sign an informed consent.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Indiana University School of Medicine

OTHER

Sponsor Role collaborator

National Institute of General Medical Sciences (NIGMS)

NIH

Sponsor Role lead

Principal Investigators

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David Flockhart, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Indiana University School of Medicine

Locations

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Indiana University

Indianapolis, Indiana, United States

Site Status

UMCCC

Ann Arbor, Michigan, United States

Site Status

Countries

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United States

References

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Rae JM, Goetz MP, Hayes DF, Ingle JN, Li L, Storniolo AM, Stearns V, Flockhart DA. CYP2D6 genotype and tamoxifen response. Breast Cancer Res. 2005 Jul 29;7(5):E6. doi: 10.1186/bcr1297. No abstract available.

Reference Type RESULT
PMID: 16168100 (View on PubMed)

Lim YC, Desta Z, Flockhart DA, Skaar TC. Endoxifen (4-hydroxy-N-desmethyl-tamoxifen) has anti-estrogenic effects in breast cancer cells with potency similar to 4-hydroxy-tamoxifen. Cancer Chemother Pharmacol. 2005 May;55(5):471-8. doi: 10.1007/s00280-004-0926-7. Epub 2005 Feb 1.

Reference Type RESULT
PMID: 15685451 (View on PubMed)

Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst. 2005 Jan 5;97(1):30-9. doi: 10.1093/jnci/dji005.

Reference Type RESULT
PMID: 15632378 (View on PubMed)

Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, Hayes DF, Desta Z, Flockhart DA. Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst. 2003 Dec 3;95(23):1758-64. doi: 10.1093/jnci/djg108.

Reference Type RESULT
PMID: 14652237 (View on PubMed)

Lee KH, Ward BA, Desta Z, Flockhart DA, Jones DR. Quantification of tamoxifen and three metabolites in plasma by high-performance liquid chromatography with fluorescence detection: application to a clinical trial. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 5;791(1-2):245-53. doi: 10.1016/s1570-0232(03)00218-6.

Reference Type RESULT
PMID: 12798184 (View on PubMed)

Hayes DF, Skaar TC, Rae JM, Henry NL, Nguyen AT, Stearns V, Li L, Philips S, Desta Z, Flockhart DA; Consortium on Breast Cancer Pharmacogenomics (COBRA). Estrogen receptor genotypes, menopausal status, and the effects of tamoxifen on lipid levels: revised and updated results. Clin Pharmacol Ther. 2010 Nov;88(5):626-9. doi: 10.1038/clpt.2010.143. Epub 2010 Sep 8.

Reference Type DERIVED
PMID: 20827267 (View on PubMed)

Henry NL, Rae JM, Li L, Azzouz F, Skaar TC, Desta Z, Sikora MJ, Philips S, Nguyen AT, Storniolo AM, Hayes DF, Flockhart DA, Stearns V; Consortium on Breast Cancer Pharmacogenomics Investigators. Association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. Breast Cancer Res Treat. 2009 Oct;117(3):571-5. doi: 10.1007/s10549-009-0309-1. Epub 2009 Jan 20.

Reference Type DERIVED
PMID: 19153830 (View on PubMed)

Ntukidem NI, Nguyen AT, Stearns V, Rehman M, Schott A, Skaar T, Jin Y, Blanche P, Li L, Lemler S, Hayden J, Krauss RM, Desta Z, Flockhart DA, Hayes DF; Consortium on Breast Cancer Pharmacogenomics. Estrogen receptor genotypes, menopausal status, and the lipid effects of tamoxifen. Clin Pharmacol Ther. 2008 May;83(5):702-10. doi: 10.1038/sj.clpt.6100343. Epub 2007 Aug 22.

Reference Type DERIVED
PMID: 17713466 (View on PubMed)

Related Links

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http://www.pharmgkb.org

The Pharmacogenetics and Pharmacogenomics Knowledge Base

Other Identifiers

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U01GM061373-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0208-14

Identifier Type: -

Identifier Source: org_study_id