Tamoxifen Citrate in Patients With Breast Cancer

Phase 3

• Conditions: Breast Cancer
• Interventions: Drug: tamoxifen citrate; Other: laboratory biomarker analysis; Other: pharmacological study

• Registration Number: NCT00963209
• Lead Sponsor: Centre Hospitalier Universitaire Vaudois

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.

Study Timeline

• Study Start: 2009-06
• Study First Submitted: 2009-08-20
• Study First Submitted QC: 2009-08-20
• Study First Posted: 2009-08-21
• Status Verified: 2013-07
• Last Update Submitted: 2013-07-31
• Last Update Posted: 2013-08-02
• Primary Completion: 2013-09
• Study Completion: 2013-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tamoxifen	tamoxifen citrate	-
Tamoxifen	pharmacological study	-
Tamoxifen	laboratory biomarker analysis	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (2)

Hôpitaux Universitaire de Genève; 🇨🇭 Genève, Switzerland

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Switzerland