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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00667121
• Other study ID #: MC0738
• Secondary ID: P30CA01508307-00
• Status: Active, not recruiting
• Start date: March 16, 2011
• Est. completion date: December 31, 2024

Study information

• Verified date: September 2023
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 85
• Est. completion date: December 31, 2024
• Est. primary completion date: May 12, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Depression
• Hot Flashes
• Psychosocial Effects of Cancer and Its Treatment

Intervention

Drug:
• citalopram hydrobromide

• escitalopram oxalate

• gabapentin

• sertraline hydrochloride

• tamoxifen citrate

• venlafaxine

Genetic:
• molecular genetic technique

Other:
• high performance liquid chromatography

• laboratory biomarker analysis

• pharmacological study

Procedure:
• adjuvant therapy

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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