Tamoxifen Metabolism and the Impact of Tamoxifen Dose on the Level of the Active Metabolites in Endocrine Sensitive Breast Cancer Patients
18 Years
N/A
Both
Breast Cancer
Trial Information
Tamoxifen Metabolism and the Impact of Tamoxifen Dose on the Level of the Active Metabolites in Endocrine Sensitive Breast Cancer Patients
OBJECTIVES:
Primary
- To determine how the increase of tamoxifen citrate dose influences the level of its
major metabolites in patients with hormone-sensitive breast cancer.
Secondary
- To characterize the population pharmacokinetic profile
- To investigate the role of the other CYPs
- To assess the relation between clinical symptoms and CYP2D6 genotypes and/or active
metabolites levels
- To explore the correlation between genotypes/metabolites levels and clinical outcomes
in terms of tumor relapse.
- To assess the feasibility, efficacy, and safety of concentration-guided adjustment of
tamoxifen citrate dosage.
- To conduct other exploratory analysis based on the eventual new data coming up in the
future.
OUTLINE: Patients receive oral tamoxifen citrate (at a dose of 40 mg/day) daily for 4 months
in the absence of disease progression or unacceptable toxicity.
Blood samples are collected for PK, genotyping, phenotyping, and further analysis.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of breast cancer
- Hormone-sensitive breast cancer defined as > 10% estrogen receptor and/or > 10%
progesterone receptor positivity by immunohistochemistry
- Receiving treatment with tamoxifen citrate and must be eligible for exposure to
higher doses
PATIENT CHARACTERISTICS:
- No history of deep venous thrombosis or pulmonary embolism
- No history of endometrial carcinoma
- No known history of vaginal bleeding, endometriosis, endometrial hyperplasia,
endometrial hypertrophy, and/or polyps
- Not pregnant or nursing
- No contraindication to tamoxifen citrate treatment
- No known allergy to midazolam or dextromethorphan
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Determination of CYP2D6 genotype and determination of plasma concentrations of tamoxifen citrate and its metabolites (N-desmethyl-tamoxifen, 4-hydroxy-tamoxifen and endoxifen) under the 20 mg daily and 40 mg daily schedules
Outcome Time Frame:
Jan 2013
Safety Issue:
No
Principal Investigator
Khalil Zaman, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Centre Hospitalier Universitaire Vaudois
Authority:
Switzerland: Swissmedic
Study ID:
CDR0000650376
NCT ID:
NCT00963209
Start Date:
June 2009
Completion Date:
June 2013
Related Keywords:
- Breast Cancer
- endocrine sensitive
- breast cancer
- tamoxifen
- genotyping
- phenotyping
- Pharmacokinetics
- Endoxifen
- Breast Neoplasms
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