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

This study is ongoing, but not recruiting participants.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic Identifier:
First received: April 24, 2008
Last updated: October 10, 2016
Last verified: January 2016

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 Intervention
Breast Cancer
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

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: The Effect of Antidepressants and Gabapentin on Tamoxifen Pharmacokinetics: A Prospective Study

Resource links provided by NLM:

Further study details as provided by Mayo Clinic:

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 [ Time Frame: Between 8-16 weeks ]

Estimated Enrollment: 85
Study Start Date: March 2008
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Detailed Description:


  • 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.


Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population


  • Menopausal status not specified
  • Life expectancy ≥ 16 weeks
  • No contraindication for venlafaxine, citalopram hydrobromide, escitalopram oxalate, gabapentin, or sertraline hydrochloride


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


  • 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)


  • 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


  • See Disease Characteristics
  • More than 4 weeks since prior and no concurrent medications that are known to inhibit the CYP2D6 system
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its 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
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Study Chair: Matthew P. Goetz, MD Mayo Clinic
  More Information

Responsible Party: Mayo Clinic Identifier: NCT00667121     History of Changes
Other Study ID Numbers: CDR0000585065
P30CA015083 ( US NIH Grant/Contract Award Number )
MC0738 ( Other Identifier: Mayo Clinic Cancer Center )
07-006133 ( Other Identifier: Mayo Clinic IRB )
NCI-2011-00406 ( Registry Identifier: NCI CTRP )
Study First Received: April 24, 2008
Last Updated: October 10, 2016

Keywords provided by Mayo Clinic:
psychosocial effects of cancer and its treatment
breast cancer
hot flashes

Additional relevant MeSH terms:
Breast Neoplasms
Hot Flashes
Neoplasms by Site
Breast Diseases
Skin Diseases
Behavioral Symptoms
Signs and Symptoms
Venlafaxine Hydrochloride
gamma-Aminobutyric Acid
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators processed this record on May 25, 2017