Tamoxifen Citrate in Patients With Breast Cancer

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00963209
• Other study ID #: CDR0000650376
• Secondary ID: CHUV-CEPO-TMEU-2
• Status: Recruiting
• Phase: Phase 3
• First received: August 20, 2009
• Last updated: July 31, 2013
• Start date: June 2009
• Est. completion date: December 2013

Study information

• Verified date: July 2013
• Source: Centre Hospitalier Universitaire Vaudois
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: December 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• tamoxifen citrate

Other:
• laboratory biomarker analysis

• pharmacological study

Locations

Country	Name	City	State
Switzerland	Hôpitaux Universitaire de Genève	Genève
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Vaudois

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Patients' characteristics		prospectively	No
Secondary	Tumor characteristics		prospectively	No
Secondary	Cancer treatments history		prospectively	No
Secondary	CYP3A4 (phenotype), and possibly other cytochromes involved in the metabolism and transport of drugs		prospectively	No
Secondary	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	No
Secondary	Concomitant medication		prospectively	No
Secondary	Presence and quantitation of clinical symptoms		prospectively	No
Secondary	Detection and classification of general comorbidities and side effects according to NCI-CTC v3.0		prospectively	Yes
Secondary	Detection of tumor relapse during the observation period of the study		prospectively	No