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

Completed

• Conditions: Associations Between Genetic Data and Docetaxel Toxicity; CYP3A Phenotyping; Docetaxel Toxicity; CYP3A5 and MDR1 Genotyping
• Interventions: Drug: docetaxel + CEF

• Registration Number: NCT01110291
• Lead Sponsor: University of Turku

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2003-04
• Primary Completion: 2004-01
• Study Completion: 2009-03
• Status Verified: 2010-04
• Study First Submitted: 2010-04-22
• Study First Submitted QC: 2010-04-22
• Study First Posted: 2010-04-26
• Last Update Submitted: 2010-04-26
• Last Update Posted: 2010-04-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 20

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Breast cancer	docetaxel + CEF	Twenty patients with verified high risk breast cancer will be included in the study.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
survival		No specific outcome measures. Survival data was collected and compared with the data from genotyping.

Trial Locations

Locations (1)

Turku University Hospital; 🇫🇮 Turku, Finland