Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01110291
Recruitment Status : Completed
First Posted : April 26, 2010
Last Update Posted : April 27, 2010
Sponsor:
Collaborators:
Sanofi
Turku University Hospital
Vaasa Central Hospital, Vaasa, Finland
medbase Oy Ltd
Information provided by:
University of Turku

Tracking Information
First Submitted Date April 22, 2010
First Posted Date April 26, 2010
Last Update Posted Date April 27, 2010
Study Start Date April 2003
Actual Primary Completion Date January 2004   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 22, 2010)
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.
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT01110291 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: April 22, 2010)
survival
No specific outcome measures. Survival data was collected and compared with the data from genotyping.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Study of Usefulness of Genotyping to Predict Docetaxel Exposure and Adverse Events
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
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 Provided
Study Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Blood samples for genotyping and phenotyping as well as analysis of docetaxel concentrations.
Sampling Method Probability Sample
Study Population Twenty patients with verified high risk breast cancer.
Condition
  • CYP3A Phenotyping
  • CYP3A5 and MDR1 Genotyping
  • Docetaxel Toxicity
  • Associations Between Genetic Data and Docetaxel Toxicity
Intervention 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.

Study Groups/Cohorts Breast cancer
Twenty patients with verified high risk breast cancer will be included in the study.
Intervention: Drug: docetaxel + CEF
Publications * Hilli J, Sailas L, Jyrkkiö S, Pyrhönen S, Laine K. NCT01110291: induction of CYP3A activity and lowered exposure to docetaxel in patients with primary breast cancer. Cancer Chemother Pharmacol. 2011 Jun;67(6):1353-62. doi: 10.1007/s00280-010-1426-6. Epub 2010 Aug 27.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: April 22, 2010)
20
Original Actual Enrollment Same as current
Actual Study Completion Date March 2009
Actual Primary Completion Date January 2004   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Finland
Removed Location Countries  
 
Administrative Information
NCT Number NCT01110291
Other Study ID Numbers XRP 6976A/6022
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Johanna Hilli, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
Study Sponsor University of Turku
Collaborators
  • 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
PRS Account University of Turku
Verification Date April 2010