Breast Cancer
Conditions
Keywords
endocrine sensitive, breast cancer, tamoxifen, genotyping, phenotyping, Pharmacokinetics, Endoxifen
Brief summary
RATIONALE: Estrogen can promote growth of endocrine sensitive breast cancer cells. Endocrine therapy with tamoxifen citrate may fight breast cancer by blocking the use of estrogen by the tumor cells. Pharmacokinetics and -genomics can have an impact on the efficacy of the treatment. PURPOSE: This phase III trial is studying blood samples to see if the level of active metabolites of tamoxifen can be improved in patients with breast cancer.
Detailed description
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.
Interventions
DRUGtamoxifen citrate
OTHERlaboratory biomarker analysis
OTHERpharmacological study
Sponsors
Centre Hospitalier Universitaire Vaudois
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 | Jan 2013 |
Secondary
| Measure | Time frame |
|---|---|
| Tumor characteristics | prospectively |
| Cancer treatments history | prospectively |
| CYP3A4 (phenotype), and possibly other cytochromes involved in the metabolism and transport of drugs | prospectively |
| Characteristics of drug intake (date of tx initiation, current dosage and frequency, time of last intake) along with patient-reported adherence, assessed by questionnaire | prospectively |
| Patients' characteristics | prospectively |
| Presence and quantitation of clinical symptoms | prospectively |
| Detection and classification of general comorbidities and side effects according to NCI-CTC v3.0 | prospectively |
| Detection of tumor relapse during the observation period of the study | prospectively |
| Concomitant medication | prospectively |
Countries
Switzerland
Outcome results
None listed