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 currently recruiting participants.
Verified March 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00667121
First received: April 24, 2008
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

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
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

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 [ Designated as safety issue: No ]

Estimated Enrollment: 85
Study Start Date: March 2008
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00667121

Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202-5289
Contact: Clinical Trials Office - Indiana University Cancer Center    317-274-2552      
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce    410-955-8804    jhcccro@jhmi.edu   
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109-0942
Contact: Clinical Trials Office - University of Michigan Comprehensive    800-865-1125      
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Matthew P. Goetz, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Matthew P. Goetz, M.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00667121     History of Changes
Other Study ID Numbers: CDR0000585065, P30CA015083, MC0738, 07-006133, NCI-2011-00406
Study First Received: April 24, 2008
Last Updated: March 20, 2014
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Breast Neoplasms
Depression
Depressive Disorder
Hot Flashes
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Behavioral Symptoms
Mood Disorders
Mental Disorders
Signs and Symptoms
Citalopram
Venlafaxine
Sertraline
Dexetimide
Gabapentin
Tamoxifen
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 15, 2014