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

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00667121

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:	Interventional
Study Design:	Treatment
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 National Cancer Institute (NCI):

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:	July 2009 (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

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
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 Cancer Center	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:

Matthew P. Goetz, MD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000585065, MAYO-MC0738
Study First Received:	April 24, 2008
Last Updated:	August 4, 2009
ClinicalTrials.gov Identifier:	NCT00667121 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

psychosocial effects of cancer and its treatment
breast cancer
hot flashes
depression

Additional relevant MeSH terms:

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Cholinergic Antagonists
Gabapentin
Anti-Dyskinesia Agents
Hormone Antagonists
Physiological Effects of Drugs
Hot Flashes
Hormones, Hormone Substitutes, and Hormone Antagonists
Calcium Channel Blockers
Excitatory Amino Acid Agents
Bone Density Conservation Agents
Cholinergic Agents
Membrane Transport Modulators
Estrogen Receptor Modulators

Neoplasms by Site
Therapeutic Uses
Venlafaxine
Antidepressive Agents, Second-Generation
Dexetimide
Antidepressive Agents
Breast Diseases
Tranquilizing Agents
Depression
Antineoplastic Agents, Hormonal
Breast Neoplasms
Depressive Disorder
Tamoxifen
Behavioral Symptoms
Neoplasms

ClinicalTrials.gov processed this record on November 27, 2009