Tamoxifen in Women With Breast Cancer and in Women at High-Risk of Breast Cancer Who Are Receiving Venlafaxine, Citalopram, Escitalopram, Gabapentin, or Sertraline
Overview[ - collapse ][ - ]
| 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. |
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| Condition | Breast Cancer Depression Hot Flashes Psychosocial Effects of Cancer and Its Treatment |
| Intervention | 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 |
| Phase | N/A |
| Sponsor | Mayo Clinic |
| Responsible Party | Mayo Clinic |
| ClinicalTrials.gov Identifier | NCT00667121 |
| First Received | April 24, 2008 |
| Last Updated | March 20, 2014 |
| Last verified | March 2014 |
Tracking Information[ + expand ][ + ]
| First Received Date | April 24, 2008 |
|---|---|
| Last Updated Date | March 20, 2014 |
| Start Date | March 2008 |
| Estimated Primary Completion Date | Not Provided |
| Current 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] |
| Current Secondary Outcome Measures | Not Provided |
Descriptive Information[ + expand ][ + ]
| Brief Title | Tamoxifen in Women With Breast Cancer and in Women at High-Risk of Breast Cancer Who Are Receiving Venlafaxine, Citalopram, Escitalopram, Gabapentin, or Sertraline |
|---|---|
| Official Title | The Effect of Antidepressants and Gabapentin on Tamoxifen Pharmacokinetics: A Prospective Study |
| 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. |
| 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 |
| Study Phase | N/A |
| Study Design | Observational Model: Case Control, Time Perspective: Cross-Sectional |
| Condition |
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| Intervention | 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 Arm (s) | Not Provided |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Recruiting |
|---|---|
| Estimated Enrollment | 85 |
| Estimated Completion Date | Not Provided |
| Estimated Primary Completion Date | September 2014 |
| Eligibility 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 |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00667121 |
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| Other Study ID Numbers | CDR0000585065 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | Mayo Clinic |
| Study Sponsor | Mayo Clinic |
| Collaborators | National Cancer Institute (NCI) |
| Investigators | Study Chair: Matthew P. Goetz, MD Mayo Clinic |
| Verification Date | March 2014 |
Locations[ + expand ][ + ]
| Indiana University Melvin and Bren Simon Cancer Center | Indianapolis, Indiana, United States, 46202-5289 Contact: Clinical Trials Office - Indiana University Cancer Center | 317-274-2552Recruiting |
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| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland, United States, 21231-2410 Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce | 410-955-8804 | jhcccro@jhmi.eduRecruiting |
| University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan, United States, 48109-0942 Contact: Clinical Trials Office - University of Michigan Comprehensive | 800-865-1125Recruiting |
| Mayo Clinic | Rochester, Minnesota, United States, 55905 Contact: Mayo Clinic Clinical Trials Office | 507-538-7623Recruiting |