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

NCT02484677 | Completed Phase 4

• 3 other identifiers: 2014-412014-005536-34RCAPHM14_0370
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Patients With Head and Neck Cancer (ORL)

Outcome Measures

Primary Outcomes (2)

• Determination of 5-FU (5-Fluorouracile)

  Concentration of 5-FU in nanograms per milliliter. Circulating 5-FU will be quantified by immunoassay.

  24 months

• Toxicities

  will be graded according to Common toxicity Criteria (CTC) 2.0 standards.

  24 months

Study Arms (1)

Head and neck cancer patient

EXPERIMENTAL

Association of Docetaxel, Cisplatin, 5-Fluorouracile for pharmacokinetic evaluation

Drug: Cisplatin; Drug: Docetaxel; Drug: 5-Fluorouracile

Interventions

Cisplatin DRUG

Antineoplastic cytostatic. Blood sampling for pharmacokinetic evaluation

Head and neck cancer patient

Docetaxel DRUG

Taxanes. Blood sampling for pharmacokinetic evaluation

Head and neck cancer patient

5-Fluorouracile DRUG

Antineoplastic and immunomodulating agents. Blood sampling for pharmacokinetic evaluation

Head and neck cancer patient

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique Hôpitaux de Marseille

Marseille, 13354, France

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Cisplatin; Docetaxel; Fluorouracil

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Urielle DESALBRES, Director

  Assistance Publique Hôpitaux de Marseille

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2015
• First Posted: June 30, 2015
• Study Start: July 15, 2015
• Primary Completion: January 25, 2017
• Study Completion: May 25, 2023
• Last Updated: May 26, 2023

Record last verified: 2023-05

Locations

FR (1)