CYP3A PhenotypingDocetaxelNCT01110291
Study of Usefulness of Genotyping to Predict Docetaxel Exposure and Adverse Events
An observational study of CYP3A Phenotyping and CYP3A5 and MDR1 Genotyping, run by University of Turku at 1 site in Finland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years, women only
- Conditions the study is for
- CYP3A Phenotyping, CYP3A5 and MDR1 Genotyping, Docetaxel Toxicity
- What is being tested?
- docetaxel + CEF
- Type of treatment
- Injection or infusion
- How many people
- 20 participants
- Where
- 1 siteFinland
- Study dates
- Apr 2003to Mar 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Women only
- No healthy volunteers
- Adult
Study population: Twenty patients with verified high risk breast cancer.
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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:
Read more
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
- Being tested
- docetaxel + CEF
- Keywords
- docetaxel toxicity, CYP3A activity, CYP3A5, MDR1, peroral midazolam
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
docetaxel + CEFDrug
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 group | Role | What they receive |
|---|---|---|
| Breast cancer | Twenty patients with verified high risk breast cancer will be included in the study. Receives: Drug: docetaxel + CEF |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
No specific outcome measures. Survival data was collected and compared with the data from genotyping.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2010 (estimated)
- Study startApr 2003
- Primary completionJan 2004
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CYP3A PhenotypingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Turku
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi, Turku University Hospital, Vaasa Central Hospital, Vaasa, Finland, medbase Oy Ltd
- Investigators
- Johanna Hilli, MD, PhD, Principal investigator, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, FinlandLiisa Sailas, MD, Study chair, Department of Oncology, Vaasa Central Hospital, Vaasa, FinlandSirkku Jyrkkiö, MD, PhD, Study chair, Department of Oncology and Radiotherapy, Turku University Hospital, Turku, FinlandSeppo Pyrhönen, MD, PhD, Study chair, Department of Oncology and Radiotherapy, Turku University Hospital, Turku, FinlandKari Laine, MD, PhD, Study chair, medbase Oy Ltd, Turku, Finland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01110291
- Sponsor's protocol ID
- XRP 6976A/6022
- Acronym
- Docetaxel
- Status last verified
- Apr 2010
- First submitted
- 22 Apr 2010
- Last updated
- 27 Apr 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 20798939
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01110291
- Acronym / sponsor ID
- Docetaxel / XRP 6976A/6022
- 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
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of TurkuUniversity, hospital or other
- Collaborators
- Sanofi, Turku University Hospital, Vaasa Central Hospital, Vaasa, Finland, medbase Oy Ltd
- Study start
- Apr 2003
- Primary completion
- Jan 2004 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 26 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Breast cancer | – | Drug: docetaxel + CEFTwenty patients with verified high risk breast cancer will be included in the study. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Twenty patients with verified high risk breast cancer.
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (14 listed)
- Poor performance status,>=2 according to WHO
- Inadequate bone marrow reserve defined as:
- Inadequate liver function defined as:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| docetaxel + CEFDocetaxel 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. | Drug | Breast cancer |
Primary outcome
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.
1 secondary outcome
survival
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2010.
- Derived from this study: PubMed 20798939Hilli 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Johanna Hilli, MD, PhD principal investigator
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
Liisa Sailas, MD study chair
Department of Oncology, Vaasa Central Hospital, Vaasa, Finland
Sirkku Jyrkkiö, MD, PhD study chair
Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of CYP3A Phenotyping and CYP3A5 and MDR1 Genotyping, run by University of Turku at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
docetaxel toxicity. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01110291, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2010.