Clinical trial NCT00963209: Tamoxifen Citrate in Patients With Breast Cancer
Official title: Tamoxifen Metabolism and the Impact of Tamoxifen Dose on the Level of the Active Metabolites in Endocrine Sensitive Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Keywords: endocrine sensitive
breast cancer
tamoxifen
genotyping
phenotyping
Pharmacokinetics
Endoxifen
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
First posted: 2009-08-21
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
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
timeFrame: Jan 2013
Secondary outcomes:
measure: Patients' characteristics
timeFrame: prospectively
measure: Tumor characteristics
timeFrame: prospectively
measure: Cancer treatments history
timeFrame: prospectively
measure: CYP3A4 (phenotype), and possibly other cytochromes involved in the metabolism and transport of drugs
timeFrame: prospectively
measure: Characteristics of drug intake (date of tx initiation, current dosage and frequency, time of last intake) along with patient-reported adherence, assessed by questionnaire
timeFrame: prospectively
measure: Concomitant medication
timeFrame: prospectively
measure: Presence and quantitation of clinical symptoms
timeFrame: prospectively
measure: Detection and classification of general comorbidities and side effects according to NCI-CTC v3.0
timeFrame: prospectively
measure: Detection of tumor relapse during the observation period of the study
timeFrame: prospectively
Other outcomes:
Locations:
city: Genève
country: Switzerland
facility: Hôpitaux Universitaire de Genève
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois
name: Khalil Zaman, MD
role: PRINCIPAL_INVESTIGATOR
References: