Tamoxifen in Women With Breast Cancer and in Women at High-Risk of Breast Cancer Who Are Receiving Venlafaxine, Citalopram, Escitalopram, Gabapentin, or Sertraline
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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 |
- 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: | June 2013 (Final data collection date for primary outcome measure) |
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 |
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
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| 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 | |
| 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: | January 18, 2013 |
| 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 May 22, 2013