Patients With Head and Neck Cancer (ORL)Phase 45-FUNCT02484677
Pharmacokinetics and Pharmacogenetics-based Adaptive Dosing of 5-fu (5-Fluorouracile) in Head & Neck Cancer Patient Undergoing Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) Therapy
A Phase 4 study testing Cisplatin, Docetaxel and 5-Fluorouracile in people with Patients With Head and Neck Cancer (ORL), run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial summary
Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) is a mainstay for treating head and neck cancers, but elderly or fragile patients are often precluded because of the risk of severe toxicities associated with this protocol. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Patients With Head and Neck Cancer (ORL)
- What is being tested?
- Cisplatin, Docetaxel and 5-Fluorouracile
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteFrance
- Study dates
- 15 Jul 2015to 25 May 2023
- Phase
- Phase 4
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 and ≤ 80 years.
- Squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, larynx, nasopharynx).
- Locally advanced stage (III, IVa or IVb).
- The patient must have received the information note and signing the informed consent, as well as being spent in multidisciplinary meeting after which treatment with TPF (Docetaxel, Cisplatin, 5-Fluorouracile) induction chemotherapy was proposed.
- Performance Status less than or equal to 2 (WHO performance index).
- The patient must be affiliated to a social security scheme and followed in one of the participating centers.
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- Patients polymorphonuclear neutrophil greater than or equal to 1000 / mm3, platelets greater than or equal to 100 000 / mm3, hemoglobin greater than or equal to 8 g / dl, transaminases less than or equal to 1.5 times the normal, total bilirubin or equal 1.5 times the normal creatinine clearance in the upper or equal to 50 ml / min Modification of Diet in Renal Disease (MDRD)
- Satisfactory heart function
- Patients must be able to submit to the rhythm of visits, treatment plan, laboratory balances and other study procedures.
Who cannot join
- Patient > 80 years.
- Patients with uncontrolled infection that could compromise participation in the study.
- Patients with other serious concomitant diseases and / or uncontrolled that could compromise participation in the study.
- Patients with serum bilirubin> under limit normal and / or Alanine Transaminase (ALAT) and Aspartate Transaminase (AST) 3.5 times the under limit normal with alkaline phosphatase greater than 6 times the under limit normal.
- Cardiovascular disease or clinically significant cardiovascular disorder in the judgment of the investigator, such as, but not limited to uncontrolled hypertension, congestive heart failure The New York Heart Association (NYHA) classification> III), unstable angina, myocardial infarction in 6 months prior to treatment, uncontrolled arrhythmias, chronic liver or renal disease, severely impaired lung function.
- Disorders significant acute gastrointestinal or recent with a major symptom of diarrhea, such as Crohn's disease, malabsorption syndrome or diarrhea Common toxicity Criteria for Adverse Events (CTCAE) grade> 1 whatever aetiology.
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- Performance Status and / or laboratory tests incompatible with chemotherapy using cisplatin, docetaxel and 5-fluorouracile (5-FU)
- Inability to submit to medical monitoring test for geographical reasons, family, social or psychological.
- Patients refusing to participate in biological assessments.
- Persons deprived of liberty or guardianship.
- Pregnant women or likely to be at the time of enrollment or during breastfeeding.
- Free, informed and signed not obtained.
Trial locations and contacts
1 site in 1 country.
About this study
Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) is a mainstay for treating head and neck cancers, but elderly or fragile patients are often precluded because of the risk of severe toxicities associated with this protocol. DPD (Dihydro Pyrimidine Dehydrogenase) deficiency is a pharmacogenetic syndrome responsible for most of the severe/lethal toxicities showing in 5-FU (5-Fluorouracile)-treated patients, and our institute has developed a strategy for the routine determination of Dihydro Pyrimidine Dehydrogenase (DPD) status prior to starting giving the 5-FU so as to roughly adapt drug dosage according to the Dihydro Pyrimidine Dehydrogenase (DPD) status. This project aims at developing a Bayesian strategy to further individualize 5-FU dosing to reach a target exposure of area under curve (AUC). To this end, 100 patients with head and neck cancer and scheduled for a Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) regimen will be included.
Read the detailed description
Crop the plasma exposure of 5-FU (5-Fluorouracile) around a predefined target area under the curve 30 (AUC30) in patients with head and neck cancer treated with Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) protocols and correlate adaptive Bayesian procedure to tolerability.
- Develop a population die from a group of 20 patients for which a pharmacokinetic study will be carried out
- Evaluate obtaining effective concentration of 5-FU in the context of a Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) protocol adapted by the Bayesian procedure.
- Compare recommendations in terms of dosage adjustment of Bayesian approach with the recommendations of a simplified graphical approach.
- Test the measure of Dihydro Pyrimidine Dehydrogenase (DPD) activity Dihydrouracil/Uracile (UH2 / U ratio) as a co-variable adjustment of 5-Fluorouracile (5-FU) regimens in Pharmacogenomics/Pharmacokinetic (PGx / PK) model.
- Evaluate a prototype of urinary dipsticks for the early detection of toxicity from the assay as a marker of Dihydro Pyrimidine Dehydrogenase (DPD) activity.
- Assess the cost-benefit of dosage targeting, in terms of reduction resulting costs to the management of chemotherapy-induced toxicities.
- Conditions
- Patients With Head and Neck Cancer (ORL)
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CisplatinDrug
Antineoplastic cytostatic. Blood sampling for pharmacokinetic evaluation
DocetaxelDrug
Taxanes. Blood sampling for pharmacokinetic evaluation
5-FluorouracileDrug
Antineoplastic and immunomodulating agents. Blood sampling for pharmacokinetic evaluation
| Study group | Role | What they receive |
|---|---|---|
| Head and neck cancer patient | Experimental | Association of Docetaxel, Cisplatin, 5-Fluorouracile for pharmacokinetic evaluation Receives: Drug: Cisplatin; Drug: Docetaxel; Drug: 5-Fluorouracile |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of 5-FU (5-Fluorouracile)
Concentration of 5-FU in nanograms per milliliter. Circulating 5-FU will be quantified by immunoassay.
Measured: 24 months
Toxicities
will be graded according to Common toxicity Criteria (CTC) 2.0 standards.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2015 (estimated)
- Study start15 Jul 2015
- Primary completion25 Jan 2017
- Study completion25 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Patients With Head and Neck Cancer (ORL)Studies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Urielle DESALBRES, Director, Study director, Assistance Publique Hôpitaux de Marseille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02484677
- Sponsor's protocol ID
- 2014-41
- Other IDs
- 2014-005536-34, RCAPHM14_0370, 2014
- Acronym
- 5-FU
- Status last verified
- May 2023
- First submitted
- 22 Jun 2015
- Last updated
- 26 May 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Pharmacogenetics-based Adaptive Dosing of 5-fu (5-Fluorouracile) in Head & Neck Cancer Patient Undergoing Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) Therapy
- ClinicalTrials.gov ID
- NCT02484677
- Acronym / sponsor ID
- 5-FU / 2014-41
- Conditions
- Patients With Head and Neck Cancer (ORL)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- 15 Jul 2015 (actual)
- Primary completion
- 25 Jan 2017 (actual)
- Study completion
- 25 May 2023 (actual)
- First posted
- 30 Jun 2015 (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.
Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) is a mainstay for treating head and neck cancers, but elderly or fragile patients are often precluded because of the risk of severe toxicities associated with this protocol. DPD (Dihydro Pyrimidine Dehydrogenase) deficiency is a pharmacogenetic syndrome responsible for most of the severe/lethal toxicities showing in 5-FU (5-Fluorouracile)-treated patients, and our institute has developed a strategy for the routine determination of Dihydro Pyrimidine Dehydrogenase (DPD) status prior to starting giving the 5-FU so as to roughly adapt drug dosage according to the Dihydro Pyrimidine Dehydrogenase (DPD) status. This project aims at developing a Bayesian strategy to further individualize 5-FU dosing to reach a target exposure of area under curve (AUC). To this end, 100 patients with head and neck cancer and scheduled for a Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) regimen will be included.
Detailed description
Crop the plasma exposure of 5-FU (5-Fluorouracile) around a predefined target area under the curve 30 (AUC30) in patients with head and neck cancer treated with Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) protocols and correlate adaptive Bayesian procedure to tolerability.
- Develop a population die from a group of 20 patients for which a pharmacokinetic study will be carried out
- Evaluate obtaining effective concentration of 5-FU in the context of a Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) protocol adapted by the Bayesian procedure.
- Compare recommendations in terms of dosage adjustment of Bayesian approach with the recommendations of a simplified graphical approach.
- Test the measure of Dihydro Pyrimidine Dehydrogenase (DPD) activity Dihydrouracil/Uracile (UH2 / U ratio) as a co-variable adjustment of 5-Fluorouracile (5-FU) regimens in Pharmacogenomics/Pharmacokinetic (PGx / PK) model.
- Evaluate a prototype of urinary dipsticks for the early detection of toxicity from the assay as a marker of Dihydro Pyrimidine Dehydrogenase (DPD) activity.
- Assess the cost-benefit of dosage targeting, in terms of reduction resulting costs to the management of chemotherapy-induced toxicities.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Head and neck cancer patient | Experimental | Drug: Cisplatin, Drug: Docetaxel, Drug: 5-FluorouracileAssociation of Docetaxel, Cisplatin, 5-Fluorouracile for pharmacokinetic evaluation |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age > 18 and ≤ 80 years.
- Squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, larynx, nasopharynx).
- Locally advanced stage (III, IVa or IVb).
- The patient must have received the information note and signing the informed consent, as well as being spent in multidisciplinary meeting after which treatment with TPF (Docetaxel, Cisplatin, 5-Fluorouracile) induction chemotherapy was proposed.
- Performance Status less than or equal to 2 (WHO performance index).
Key exclusion criteria (12 listed)
- Patient > 80 years.
- Patients with uncontrolled infection that could compromise participation in the study.
- Patients with other serious concomitant diseases and / or uncontrolled that could compromise participation in the study.
- Patients with serum bilirubin> under limit normal and / or Alanine Transaminase (ALAT) and Aspartate Transaminase (AST) 3.5 times the under limit normal with alkaline phosphatase greater than 6 times the under limit normal.
- Cardiovascular disease or clinically significant cardiovascular disorder in the judgment of the investigator, such as, but not limited to uncontrolled hypertension, congestive heart failure The New York Heart Association (NYHA) classification> III), unstable angina, myocardial infarction in 6 months prior to treatment, uncontrolled arrhythmias, chronic liver or renal disease, severely impaired lung function.
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 |
|---|---|---|
| CisplatinAntineoplastic cytostatic. Blood sampling for pharmacokinetic evaluation | Drug | Head and neck cancer patient |
| DocetaxelTaxanes. Blood sampling for pharmacokinetic evaluation | Drug | Head and neck cancer patient |
| 5-FluorouracileAntineoplastic and immunomodulating agents. Blood sampling for pharmacokinetic evaluation | Drug | Head and neck cancer patient |
Primary outcome
Determination of 5-FU (5-Fluorouracile)
Time frame: 24 months
Concentration of 5-FU in nanograms per milliliter. Circulating 5-FU will be quantified by immunoassay.
Toxicities
Time frame: 24 months
will be graded according to Common toxicity Criteria (CTC) 2.0 standards.
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 26 May 2023.
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.
Urielle DESALBRES, Director study director
Assistance Publique Hôpitaux de Marseille
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Cisplatin, Docetaxel and 5-Fluorouracile in people with Patients With Head and Neck Cancer (ORL), run by Assistance Publique Hopitaux De Marseille at 1 site in France.
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 9 inclusion and 12 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 26 May 2023. 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 France. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Determination of 5-FU (5-Fluorouracile) (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 May 2023.