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

This study has been completed.
Sponsor:
Collaborators:
Sanofi
Turku University Hospital
Vaasa Central Hospital, Vaasa, Finland
medbase Oy Ltd
Information provided by:
University of Turku
ClinicalTrials.gov Identifier:
NCT01110291
First received: April 22, 2010
Last updated: April 26, 2010
Last verified: April 2010
  Purpose

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.


Condition Intervention
CYP3A Phenotyping
CYP3A5 and MDR1 Genotyping
Docetaxel Toxicity
Associations Between Genetic Data and Docetaxel Toxicity
Drug: docetaxel + CEF

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Turku:

Primary Outcome Measures:
  • docetaxel toxicity [ Designated as safety issue: Yes ]
    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:
  • survival [ Designated as safety issue: No ]
    No specific outcome measures. Survival data was collected and compared with the data from genotyping.


Biospecimen Retention:   Samples With DNA

Blood samples for genotyping and phenotyping as well as analysis of docetaxel concentrations.


Enrollment: 20
Study Start Date: April 2003
Study Completion Date: March 2009
Primary Completion Date: January 2004 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Twenty patients with verified high risk breast cancer.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01110291

Locations
Finland
Turku University Hospital
Turku, Finland, 20521
Sponsors and Collaborators
University of Turku
Sanofi
Turku University Hospital
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
  More Information

No publications provided by University of Turku

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Johanna Hilli, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
ClinicalTrials.gov Identifier: NCT01110291     History of Changes
Other Study ID Numbers: XRP 6976A/6022
Study First Received: April 22, 2010
Last Updated: April 26, 2010
Health Authority: Finland: Finnish Medicines Agency

Keywords provided by University of Turku:
docetaxel toxicity
CYP3A activity
CYP3A5
MDR1
peroral midazolam

Additional relevant MeSH terms:
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014