Tamoxifen Citrate in Patients With Breast Cancer

This study is currently recruiting participants.
Verified July 2013 by Centre Hospitalier Universitaire Vaudois
Sponsor:
Information provided by (Responsible Party):
Dr K. Zaman, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier:
NCT00963209
First received: August 20, 2009
Last updated: July 31, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: tamoxifen citrate
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire Vaudois:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 140
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)
Arms Assigned Interventions
Experimental: Tamoxifen Drug: tamoxifen citrate Other: laboratory biomarker analysis Other: pharmacological study

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00963209

Locations
Switzerland
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   
Sponsors and Collaborators
Centre Hospitalier Universitaire Vaudois
Investigators
Principal Investigator: Khalil Zaman, MD Centre Hospitalier Universitaire Vaudois
  More Information

Additional Information:
No publications provided

Responsible Party: Dr K. Zaman, Médecin associé, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier: NCT00963209     History of Changes
Other Study ID Numbers: CDR0000650376, CHUV-CEPO-TM, EU-20973
Study First Received: August 20, 2009
Last Updated: July 31, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by Centre Hospitalier Universitaire Vaudois:
endocrine sensitive
breast cancer
tamoxifen
genotyping
phenotyping
Pharmacokinetics
Endoxifen

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents
Estrogen Antagonists

ClinicalTrials.gov processed this record on April 17, 2014