Tamoxifen Metabolism and the Impact of Tamoxifen Dose on the Level of the Active Metabolites in Endocrine Sensitive Breast Cancer Patients
Overview
- Phase
- Phase 3
- Intervention
- pharmacological study
- Conditions
- Breast Cancer
- Sponsor
- Centre Hospitalier Universitaire Vaudois
- Enrollment
- 140
- Locations
- 2
- Primary Endpoint
- 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
- Last Updated
- 12 years ago
Overview
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.
Investigators
Dr K. Zaman
Médecin associé
Centre Hospitalier Universitaire Vaudois
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Tamoxifen
Intervention: pharmacological study
Tamoxifen
Intervention: tamoxifen citrate
Tamoxifen
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
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
Time Frame: Jan 2013
Secondary Outcomes
- Patients' characteristics(prospectively)
- 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)
- Concomitant medication(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)