Pharmacokinetics and Pharmacogenetics-based Adaptive Dosing of 5-fu (5-Fluorouracile) in Head & Neck Cancer Patient Undergoing Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) Therapy (5-FU)

May 25, 2023 updated by: Assistance Publique Hopitaux De Marseille
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Urielle DESALBRES, Director
  • Phone Number: 04.91.38.27.47
  • Email: drci@ap-hm.fr

Study Contact Backup

Study Locations

  • France
      • Marseille, France, 13354
        • Assistance Publique Hopitaux de Marseille

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Head and neck cancer patient
Association of Docetaxel, Cisplatin, 5-Fluorouracile for pharmacokinetic evaluation
Drug: Cisplatin
Antineoplastic cytostatic. Blood sampling for pharmacokinetic evaluation
Drug: Docetaxel
Taxanes. Blood sampling for pharmacokinetic evaluation
Drug: 5-Fluorouracile
Antineoplastic and immunomodulating agents. Blood sampling for pharmacokinetic evaluation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
24 months
Toxicities
Time Frame: 24 months
will be graded according to Common toxicity Criteria (CTC) 2.0 standards.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique Hopitaux De Marseille

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Urielle DESALBRES, Director, Assistance Publique Hopitaux de Marseille

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 15, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 25, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 25, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 22, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 29, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 30, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 26, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 25, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2014-41
  • 2014-005536-34 (EudraCT Number)
  • RCAPHM14_0370 (Other Identifier: APHM)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Patients With Head and Neck Cancer (ORL)

Clinical Trials on Cisplatin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings