Tamoxifen in Women With Breast Cancer and in Women at High-Risk of Breast Cancer Who Are Receiving Venlafaxine, Citalopram, Escitalopram, Gabapentin, or Sertraline
RATIONALE: Studying samples of blood in the laboratory from patients receiving tamoxifen may help doctors learn more about the effects of other drugs on the level of tamoxifen in the blood.
PURPOSE: This clinical trial is studying levels of tamoxifen in the blood of women with breast cancer and in women at high risk of breast cancer who are receiving tamoxifen together with venlafaxine, citalopram, escitalopram, gabapentin, or sertraline.
Psychosocial Effects of Cancer and Its Treatment
Drug: citalopram hydrobromide
Drug: escitalopram oxalate
Drug: sertraline hydrochloride
Drug: tamoxifen citrate
Genetic: molecular genetic technique
Other: high performance liquid chromatography
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: adjuvant therapy
|Study Design:||Observational Model: Case Control
Time Perspective: Cross-Sectional
|Official Title:||The Effect of Antidepressants and Gabapentin on Tamoxifen Pharmacokinetics: A Prospective Study|
- Percent change in plasma concentrations of 4-hydroxy tamoxifen and of endoxifen after ≥ 8 weeks of concurrent administration of tamoxifen citrate and a CYP2D6 inhibitor [ Time Frame: Between 8-16 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||March 2008|
|Estimated Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
- To examine the changes in the plasma concentrations of the hydroxylated metabolite, 4-hydroxy tamoxifen, and endoxifen in women with known or at high risk for developing breast cancer who are receiving selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor therapy comprising venlafaxine, citalopram hydrobromide, escitalopram oxalate, gabapentin, or sertraline hydrochloride for the treatment of hot flashes, depression, or any other medically indicated condition.
- To evaluate whether genetic variants known to affect the activity of CYP2D6, SULT1A1, and other drug metabolizing enzymes (e.g., UGT's) involved in the biotransformation of tamoxifen citrate affect the plasma concentrations of the hydroxylated metabolites, 4-hydroxy tamoxifen and endoxifen.
OUTLINE: This is a multicenter study.
Patients receive oral tamoxifen citrate and concurrent selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) therapy comprising oral venlafaxine, citalopram hydrobromide, escitalopram oxalate, sertraline hydrochloride, or gabapentin for 8-24 weeks. Treatment continues in the absence of disease progression.
Blood samples are obtained at baseline and after completion of study therapy. Samples are evaluated by pharmacokinetic analysis to determine the effects of SSRI/SNRI study drugs on plasma concentrations of tamoxifen and its metabolites. Plasma levels of tamoxifen citrate, N-desmethyl tamoxifen, 4-OH tamoxifen, and endoxifen are measured using reverse phase high performance liquid chromatography. Blood samples are also analyzed by CYP2D6 genotyping to test for CYP2D6 gene variation (i.e., *3, *4, *6, *10, *17, and *41) in genes that encode tamoxifen-metabolizing enzymes. Additional CYP2D6 alleles, including gene duplication and gene deletion (*5) are assessed.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00667121
|United States, Indiana|
|Indiana University Melvin and Bren Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202-5289|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109-0942|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Matthew P. Goetz, MD||Mayo Clinic|