Study of Usefulness of Genotyping to Predict Docetaxel Exposure and Adverse Events (Docetaxel)

April 26, 2010 updated by: University of Turku

Activity of CYP3A and Genotypes of CYP3A5 and MDR1 as Predictors of the Clearance and Adverse Effects of Docetaxel, and the Effect of Docetaxel to CYP3A Activity in Previously Untreated Breast Cancer Patients

Twenty patients with verified high risk breast cancer will be included in the study. Patients will receive three cycles of docetaxel followed by three cycles of CEF for their adjuvant treatment. The phenotype of CYP3A and the genotype of CYP3A5 and MDR1 will be assessed. Also the effect of docetaxel in the activity of CYP3A will be measured by peroral midazolam.

Primary Object:

The primary object of this study is to define, if it is possible to predict the clearance and/ or toxicity of docetaxel by assessing

  • activity of CYP3A4 by midazolam test (CYP3A4 phenotype)
  • CYP3A5 genotype
  • MDR1 genotype

Secondary object:

The secondary object of this study is to define whether the treatment with docetaxel alters the activity of CYP3A4 enzyme in previously untreated breast cancer patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Finland
      • Turku, Finland, 20521
        • Turku University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

Twenty patients with verified high risk breast cancer.

Description

Inclusion Criteria:

Subjects may be included in the study only if they meet all of the following criteria:

  1. The patient has received information on the purpose of the study and the meaning of the treatment, and has given verbal and written consent to participate in the study. The patient is accessible for treatment and follow-up.
  2. Histologically verified diagnosis of breast cancer
  3. High risk for recurrence ( node positive or node negative if T2 with histological grade 2 or 3, or Pgr negative)
  4. No metastases
  5. Females, age =<60
  6. No concomitant regular medication which is either substrate, inducer or inhibitor of CYP3A4

Exclusion Criteria:

Subjects will be excluded from the study for any of the following reasons:

  1. Poor performance status,>=2 according to WHO

  2. Inadequate bone marrow reserve defined as:

    • hemoglobin < 100 g/L
    • leukocytes < 3.0 x 10E9/L or neutrophiles < 1.5 x 10E9/L
    • plateless < 120 x 10E9/L

  3. Inadequate liver function defined as:

    • ALAT is > 1.5 x units of normal level
    • elevated bilirubin (unless verified Gilbert´s syndrome)
    • alkaline phosphatase is > 2.5 x units of normal level
  4. History of concomitant serious physical or psychiatric disease, which makes a regular cytotoxic treatment impossible
  5. cardiac insufficience; severe arrhythmia; severe hypertension; cardiac infarction within one year or other active cardiac disease
  6. pregnant or lactating patients
  7. abuse of alcohol or any narcotic substances

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Breast cancer
Twenty patients with verified high risk breast cancer will be included in the study.
Drug: docetaxel + CEF

Docetaxel 80 mg/m² of body surface area (BSA) will be given as an i.v. infusion during 60 minutes on day 0 in a 20-day schedule. The cycle is repeated three times.

Three weeks after the last docetaxel regimen, all patients will receive the CEF-combination treatment. In CEF-combination cyclophosphamide will be given 600 mg/m²of BSA as an i.v. infusion during 15 - 30 minutes on day 0 in a 20-day schedule. This is followed by fluorouracil given 600 mg/m² of BSA as an i.v. infusion during 15 - 30 minutes . Epirubicin will be given 60 mg/m² of BSA as an i.v. infusion during 15 - 30 minutes. This combination therapy will be repeated three times.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
docetaxel toxicity
There were no specific outcome measures in this study. The chemotherapy was given in a predetermined schedule and additionally blood samples were drawn for genotyping. The adverse events were recorded and compared with the data from genotyping.

Secondary Outcome Measures

Outcome Measure
Measure Description
survival
No specific outcome measures. Survival data was collected and compared with the data from genotyping.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Turku

Collaborators

Turku University Hospital
Sanofi
Vaasa Central Hospital, Vaasa, Finland
medbase Oy Ltd

Investigators

  • Principal Investigator: Johanna Hilli, MD, PhD, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
  • Study Chair: Liisa Sailas, MD, Department of Oncology, Vaasa Central Hospital, Vaasa, Finland
  • Study Chair: Sirkku Jyrkkiö, MD, PhD, Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland
  • Study Chair: Seppo Pyrhönen, MD, PhD, Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland
  • Study Chair: Kari Laine, MD, PhD, medbase Oy Ltd, Turku, Finland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2003

Primary Completion (Actual)

January 1, 2004

Study Completion (Actual)

March 1, 2009

Study Registration Dates

First Submitted

April 22, 2010

First Submitted That Met QC Criteria

April 22, 2010

First Posted (Estimate)

April 26, 2010

Study Record Updates

Last Update Posted (Estimate)

April 27, 2010

Last Update Submitted That Met QC Criteria

April 26, 2010

Last Verified

April 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XRP 6976A/6022

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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