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

September 21, 2023 updated by: Mayo Clinic

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

85

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5289
        • Indiana University Melvin and Bren Simon Cancer Center
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0942
        • University of Michigan Comprehensive Cancer Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

PATIENT CHARACTERISTICS:

  • Menopausal status not specified
  • Life expectancy ≥ 16 weeks
  • 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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Between 8-16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Matthew P. Goetz, MD, Mayo Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 16, 2011

Primary Completion (Actual)

May 12, 2014

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

April 24, 2008

First Submitted That Met QC Criteria

April 24, 2008

First Posted (Estimated)

April 25, 2008

Study Record Updates

Last Update Posted (Actual)

September 25, 2023

Last Update Submitted That Met QC Criteria

September 21, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MC0738 (Mayo Clinic Cancer Center)
  • P30CA015083 (U.S. NIH Grant/Contract)
  • 07-006133 (Other Identifier: Mayo Clinic IRB)
  • NCI-2011-00406 (Registry Identifier: NCI CTRP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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