Tamoxifen Citrate in Patients With Breast Cancer
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.
Drug: tamoxifen citrate
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Tamoxifen Metabolism and the Impact of Tamoxifen Dose on the Level of the Active Metabolites in Endocrine Sensitive Breast Cancer Patients|
- 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 ] [ Designated as safety issue: No ]
- Patients' characteristics [ Time Frame: prospectively ] [ Designated as safety issue: No ]
- Tumor characteristics [ Time Frame: prospectively ] [ Designated as safety issue: No ]
- Cancer treatments history [ Time Frame: prospectively ] [ Designated as safety issue: No ]
- CYP3A4 (phenotype), and possibly other cytochromes involved in the metabolism and transport of drugs [ Time Frame: prospectively ] [ Designated as safety issue: No ]
- Characteristics of drug intake (date of tx initiation, current dosage and frequency, time of last intake) along with patient-reported adherence, assessed by questionnaire [ Time Frame: prospectively ] [ Designated as safety issue: No ]
- Concomitant medication [ Time Frame: prospectively ] [ Designated as safety issue: No ]
- Presence and quantitation of clinical symptoms [ Time Frame: prospectively ] [ Designated as safety issue: No ]
- Detection and classification of general comorbidities and side effects according to NCI-CTC v3.0 [ Time Frame: prospectively ] [ Designated as safety issue: Yes ]
- Detection of tumor relapse during the observation period of the study [ Time Frame: prospectively ] [ Designated as safety issue: No ]
|Study Start Date:||June 2009|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
|Experimental: Tamoxifen||Drug: tamoxifen citrate Other: laboratory biomarker analysis Other: pharmacological study|
- To determine how the increase of tamoxifen citrate dose influences the level of its major metabolites in patients with hormone-sensitive breast cancer.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00963209
|Hôpitaux Universitaire de Genève||Recruiting|
|Genève, Switzerland, 1211|
|Contact: Alexandre Bodmer, MD 41 22 382 40 14|
|Centre Hospitalier Universitaire Vaudois||Recruiting|
|Lausanne, Switzerland, 1011|
|Contact: Khalil Zaman, MD 41-21-314-0168 Khalil.Zaman@chuv.ch|
|Principal Investigator:||Khalil Zaman, MD||Centre Hospitalier Universitaire Vaudois|