Tamoxifen Citrate in Patients With Breast Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Tamoxifen Metabolism and the Impact of Tamoxifen Dose on the Level of the Active Metabolites in Endocrine Sensitive Breast Cancer Patients

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: tamoxifen citrate
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tamoxifen<br> | Drug: tamoxifen citrate<br> <br> Other: laboratory biomarker analysis<br> <br> Other: pharmacological study<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endocrine sensitive, breast cancer, tamoxifen, genotyping, phenotyping, Pharmacokinetics, Endoxifen