Breath Test for Women Receiving Tamoxifen in the Prevention or Treatment of Breast Cancer
RATIONALE: A breath test that measures enzymes may be effective in identifying women in whom tamoxifen may not be effective.
PURPOSE: This clinical trial is studying a breath test to see how well it works in women receiving tamoxifen for the prevention or treatment of breast cancer.
Drug: dextromethorphan hydrobromide
Drug: tamoxifen citrate
Other: high performance liquid chromatography
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: pharmacological study
Procedure: fluorescence imaging
|Study Design:||Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||¹³C - Dextromethorphan (DM) Breath Test for Determination of CYP2D6 Enzyme Activity in Patients Receiving Tamoxifen|
- Operating characteristics of the ¹³C-dextromethorphan (13C-DM) breath test in identifying those who are CYP2D6 genotypic poor metabolizers [ Designated as safety issue: No ]
- Correlation of the findings of the ¹³C-DM breath test with the ratio of endoxifen to N-desmethyl-tamoxifen (E/NdTAM) and with steady state plasma measurements of 4-hydroxyTAM [ Designated as safety issue: No ]
- Changes in ¹³C-DM breath test results during the course of the study, specifically for patients that initiate a CYP2D6 inhibitor [ Designated as safety issue: No ]
|Study Start Date:||May 2009|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
- To assess the operating characteristics of the ¹³C-dextromethorphan (^13 C-DM) breath test in identifying women with breast cancer (or at high risk) who are CYP2D6-genotypic poor metabolizers.
- To examine the correlation between CYP2D6 enzyme activity (as measured by the breath test) and plasma endoxifen (and 4-hydroxyTAM) levels in patients who carry one or more CYP2D6 functional alleles.
- To examine the change in CYP2D6 enzyme activity (as measured by the ¹³C-DM breath test), in patients who start a CYP2D6 inhibitor while taking tamoxifen.
- To determine whether CYP2D6 enzyme activity (as measured by the breath test) changes over time (either as a consequence of drug-induced inhibition or other).
- To measure genetic variation in additional genes that are later identified to affect the metabolism, uptake, or distribution of tamoxifen (e.g., SULT1A1, UGT).
OUTLINE: Patients receive tamoxifen citrate for 6 months. ^13C-dextromethorphan breath tests are conducted at baseline and periodically during the 6 months.
13C-dextromethorphan breath test: Patients receive oral Alka-Seltzer® Gold (ASG; citric acid, potassium bicarbonate, and sodium bicarbonate) in water, then, 15 minutes later, another ASG dose and oral ¹³C-dextromethorphan. Patients breathe into a bag 1-2 times, and the is bag sealed. ¹³CO_2 levels in the bags are measured.
Blood samples are collected at baseline and periodically for pharmacogenetic and pharmacokinetic studies by reverse phase HPLC with fluorescence detection.
After completion of study therapy, patients are followed annually for 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00873366
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Matthew P. Goetz, M.D.||Mayo Clinic|
|Principal Investigator:||Donald W. Northfelt, M.D.||Mayo Clinic|