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)
85
Enrollment
4
Locations
129
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 DiseaseIntervention/TreatmentPhase
  • 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, 2021

Outcome Measures

Primary Outcome Measures

  1. 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:
No
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

SiteCityStateCountryPostal Code
1Indiana University Melvin and Bren Simon Cancer CenterIndianapolisIndianaUnited States46202-5289
2Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreMarylandUnited States21231-2410
3University of Michigan Comprehensive Cancer CenterAnn ArborMichiganUnited States48109-0942
4Mayo ClinicRochesterMinnesotaUnited States55905

Sponsors and Collaborators

  • Mayo Clinic
  • National Cancer Institute (NCI)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00667121
Other Study ID Numbers:
  • CDR0000585065
  • P30CA015083
  • MC0738
  • 07-006133
  • NCI-2011-00406
First Posted:
Apr 25, 2008
Last Update Posted:
Oct 7, 2021
Last Verified:
Oct 1, 2021

Study Results

No Results Posted as of Oct 7, 2021