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

NCT ID: NCT01110291

Last Updated: 2010-04-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2003-04-30
• Study Completion Date: 2009-03-31

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.

Conditions

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

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Breast cancer

Twenty patients with verified high risk breast cancer will be included in the study.

docetaxel + CEF

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Turku University Hospital

OTHER_GOV

Sponsor Role: collaborator

Vaasa Central Hospital, Vaasa, Finland

OTHER

Sponsor Role: collaborator

medbase Oy Ltd

UNKNOWN

Sponsor Role: collaborator

University of Turku

OTHER

Sponsor Role: lead

Responsible Party

Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland

Principal Investigators

Johanna Hilli, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland

Liisa Sailas, MD

Role: STUDY_CHAIR

Department of Oncology, Vaasa Central Hospital, Vaasa, Finland

Sirkku Jyrkkiö, MD, PhD

Role: STUDY_CHAIR

Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland

Seppo Pyrhönen, MD, PhD

Role: STUDY_CHAIR

Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland

Kari Laine, MD, PhD

Role: STUDY_CHAIR

medbase Oy Ltd, Turku, Finland

Locations

Turku University Hospital

Turku, , Finland

Countries

Finland

References

Hilli J, Sailas L, Jyrkkio S, Pyrhonen 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.

Reference Type: DERIVED

PMID: 20798939 (View on PubMed)

Other Identifiers

XRP 6976A/6022

Identifier Type: -

Identifier Source: org_study_id