Tamoxifen in Women With Breast Cancer and in Women at High-Risk of Breast Cancer Who Are Receiving Venlafaxine, Citalopram, Escitalopram, Gabapentin, or Sertraline

Sponsor

Mayo Clinic (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00667121

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

141

Anticipated Duration (Months)

21.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Depression Hot Flashes Psychosocial Effects of Cancer and Its Treatment	Drug: citalopram hydrobromide Drug: escitalopram oxalate Drug: gabapentin Drug: sertraline hydrochloride Drug: tamoxifen citrate Drug: venlafaxine Genetic: molecular genetic technique Other: high performance liquid chromatography Other: laboratory biomarker analysis Other: pharmacological study Procedure: adjuvant therapy

Detailed Description

OBJECTIVES:

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

85 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

The Effect of Antidepressants and Gabapentin on Tamoxifen Pharmacokinetics: A Prospective Study

Actual Study Start Date :

Mar 16, 2011

Actual Primary Completion Date :

May 12, 2014

Anticipated Study Completion Date :

Dec 15, 2022

Outcome Measures

Primary Outcome Measures

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 [Between 8-16 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Meets 1 of the following criteria:
Diagnosis of invasive or non-invasive breast cancer
At high risk for developing breast cancer
Has been receiving tamoxifen citrate for at least 4 weeks without any breaks either for the prevention or the adjuvant treatment of invasive or non-invasive breast cancer at a dose of 20 mg/day
Planning to begin medical therapy with one of the following drugs, as determined by physician:
Venlafaxine
Citalopram hydrobromide
Escitalopram oxalate
Sertraline hydrochloride
Gabapentin
Agrees to continue tamoxifen citrate during the proposed minimum study period of 8 weeks
Known CYP2D6 genotype
Not known to be a CYP2D6 poor metabolizer (defined as homozygous for one of the following CYP2D6 null alleles: *3, *4, *5, *6) as determined from the baseline genotype test
Estrogen receptor-positive disease (for patients with breast cancer)

PATIENT CHARACTERISTICS:

Menopausal status not specified
Life expectancy ≥ 16 weeks
Willing to return to primary site of enrollment for follow-up, including any of the following:
Mayo Clinic Rochester
Indiana University
University of Michigan
Johns Hopkins
Fairfax-Northern Virginia Hematology-Oncology, PC
No contraindication for venlafaxine, citalopram hydrobromide, escitalopram oxalate, gabapentin, or sertraline hydrochloride

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
More than 4 weeks since prior and no concurrent medications that are known to inhibit the CYP2D6 system

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
2	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
3	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
4	Mayo Clinic	Rochester	Minnesota	United States	55905