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

Summary

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.

Conditions

• CYP3A Phenotyping
• CYP3A5 and MDR1 Genotyping
• Docetaxel Toxicity
• Associations Between Genetic Data and Docetaxel Toxicity

Interventions

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.

Sponsors & Collaborators

• Sanofi

  collaborator INDUSTRY

• Turku University Hospital

  collaborator OTHER_GOV

• Vaasa Central Hospital, Vaasa, Finland

  collaborator OTHER

• medbase Oy Ltd

  collaborator UNKNOWN

• University of Turku

  lead OTHER

Principal Investigators

• Johanna Hilli, MD, PhD · Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland

• Liisa Sailas, MD · Department of Oncology, Vaasa Central Hospital, Vaasa, Finland

• Sirkku Jyrkkiö, MD, PhD · Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland

• Seppo Pyrhönen, MD, PhD · Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland

• Kari Laine, MD, PhD · medbase Oy Ltd, Turku, Finland

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2003-04-30

Primary Completion

2004-01-31

Completion

2009-03-31

Countries

• Finland

Study Locations