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

NCT01110291 | Completed

• 1 other identifier: XRP 6976A/6022
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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

Keywords

docetaxel toxicity; CYP3A activity; CYP3A5; MDR1; peroral midazolam

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• survival

Study Arms (1)

Breast cancer

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

Drug: docetaxel + CEF

Interventions

docetaxel + CEF 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.

Breast cancer

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Twenty patients with verified high risk breast cancer.

You may qualify if:

• Subjects may be included in the study only if they meet all of the following criteria:
• 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.
• Histologically verified diagnosis of breast cancer
• High risk for recurrence ( node positive or node negative if T2 with histological grade 2 or 3, or Pgr negative)
• No metastases
• Females, age =\<60
• No concomitant regular medication which is either substrate, inducer or inhibitor of CYP3A4

You may not qualify if:

• Subjects will be excluded from the study for any of the following reasons:
• Poor performance status,\>=2 according to WHO
• 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
• 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
• History of concomitant serious physical or psychiatric disease, which makes a regular cytotoxic treatment impossible
• cardiac insufficience; severe arrhythmia; severe hypertension; cardiac infarction within one year or other active cardiac disease
• pregnant or lactating patients
• abuse of alcohol or any narcotic substances

Sponsors & Collaborators

• University of Turku: lead
• Sanofi: collaborator
• Turku University Hospital: collaborator
• Vaasa Central Hospital, Vaasa, Finland: collaborator
• medbase Oy Ltd: collaborator

Study Sites (1)

Turku University Hospital

Turku, 20521, Finland

Location

Related Publications (1)

• 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.

  PMID: 20798939 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

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

MeSH Terms

Interventions

Docetaxel; CEF regimen

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Johanna Hilli, MD, PhD

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

  PRINCIPAL INVESTIGATOR

• 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

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 22, 2010
• First Posted: April 26, 2010
• Study Start: April 1, 2003
• Primary Completion: January 1, 2004
• Study Completion: March 1, 2009
• Last Updated: April 27, 2010

Record last verified: 2010-04

Locations

FI (1)