Tamoxifen Pharmacogenetics and Clinical Effects

Breast Cancer Clinical Trial

Official title:

A Pilot Trial Correlating Metabolic Profile of Tamoxifen With Pharmacogenetic Predictors and Clinical Effects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00228930
• Other study ID #: 0208-14
• Secondary ID: UO1-GM61373-05
• Status: Completed
• Phase: Phase 4
• First received: September 27, 2005
• Last updated: September 24, 2008
• Start date: September 2002
• Est. completion date: August 2007

Study information

• Verified date: November 2007
• Source: National Institute of General Medical Sciences (NIGMS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 297
• Est. completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Breast Cancer

Intervention

Drug:
• Tamoxifen (pharmacodynamic analysis)
Tamoxifen 20mg po daily

Locations

Country	Name	City	State
United States	UMCCC	Ann Arbor	Michigan
United States	Indiana University	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of General Medical Sciences (NIGMS)	Indiana University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (5)

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 duri — View Citation

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 — View Citation

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. Epub 2005 Feb 1. — View Citation

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. — View Citation

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 Canc — View Citation

External Links

•   Drug Interactions--Cytochrome P450
•   The Division of Clinical Pharmacology, Indiana University
•   The Pharmacogenetics and Pharmacogenomics Knowledge Base