Fluoropyrimidine Tailored-dose Based on Uracil Concentration in Patients Treated for Digestive Carcinomas: Evaluation of Clinical Practice (URACILMPACT)

June 2, 2021 updated by: Hospices Civils de Lyon

Digestive carcinomas chemotherapies regimen are mostly based on fluoropyrimidine drugs (5-Fluorouracil (5-FU) or capecitabine). 5-FU is mainly catabolised by dihydropyrimidine dehydrogenase (DPD) and partial or complete DPD deficiency can cause severe adverse reactions. Different strategies have been proposed to predict DPD deficiency; the two main approaches are phenotyping the enzyme activity (directly or indirectly), or genotyping the four main polymorphisms associated with 5-FU-toxicity. In February 2018, the French medicines agency (Agence nationale de sécurité du médicament et des produits de santé, ANSM) recommended DPD genotyping for all patients receiving fluoropyrimidine-based treatment to improve its safety as compared to the European Medicines Agency (EMA)13 and others pharmacogenetics working group.

In December 2018, a new guideline from the French cancer institute (Institut National Du Cancer, INCa) and the French health authority (Haute Autorité de Santé, HAS) recommended the measurement of the uracil blood level before genotyping DPD and dose adaptation if this level is greater than 16 ng/mL. The aim herein is to assess how this recommendation has been implemented in clinical routine. 5-FU displays a dose-response relationship regarding both its efficacy and its toxicity, did tailored-dose impair the treatment efficacy as it decreased the risk of toxicity? To address that matter we conducted a retrospective study to evaluate how fluoropyrimidine dosage is adapted to uracil concentration with an emphasis on how patients outcome were affected. We compared time to failure and overall survival between patients with an uracil concentration < 16 ng/mL and > or = 16 ng/mL.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

334

Contacts and Locations

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

Study Locations

  • France
      • Lyon, France, 69004
        • Hopital de la croix rousse
      • Lyon, France, 69003
        • Hopital Edouard Heriot, Centre Hospitalier de Lyon Sud [Lyon], Hopital de la Croix Rousse [Lyon]
      • Pierre-Bénite, France, 69495
        • Centre Hospitalier de Lyon Sud

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients will be included in this retrospective study if they have digestive cancer and an uracil dosage performed between February 2018 to January 2020, and if they received at least one cycle of fluoropyrimidine-based chemotherapy in one of the three oncology departments (Hopital Edouard Heriot [Lyon], Centre Hospitalier de Lyon Sud [Lyon], Hopital de la Croix Rousse [Lyon]. The following characteristics will be review: histology, stage (localized vs metastatic disease), chemotherapy regimen, dose percentage of fluoropyrimidine, fluoropyrimidine induced-toxicity, time to failure and overall survival.

Description

Inclusion Criteria:

  • Digestive cancer
  • An uracil dosage performed between February 2018 to January 2020
  • Received at least one cycle of fluoropyrimidine-based chemotherapy in one of the three oncology departments (Hopital Edouard Heriot [Lyon], Centre Hospitalier de Lyon Sud [Lyon], Hopital de la Croix Rousse [Lyon]).

Exclusion Criteria:

  • Age limit less than 18 years
  • Not treated with fluoropyrimidine based chemotherapy
  • Missing data for uracil concentration or chemotherapy dosage

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Uracil concentration <16 ng/mL
Patients were included in this arm if they have digestive cancer and an uracil dosage <16 ng/mL performed between February 2018 to January 2020, and if they received at least one cycle of fluoropyrimidine-based chemotherapy in one of the four oncology departments (Hopital Edouard Heriot [Lyon], Centre Hospitalier de Lyon Sud [Lyon], Hopital de la Croix Rousse [Lyon].
Drug: Fluoropyrimidine treatment (5-FU or capecitabine) and dosage
In each group with an uracil dosage; at cycle 1; capecitabine or continuous 5-FU dose percentage will be evaluate retrospectively in our database
Other: Uracil dosage
For each patient, uracil concentration will be evaluate and patients will be compared based on 16 ng/mL as threshold.
Behavioral: Overall survival
For each group of patient, on 16 ng/mL as threshold for uracil concentration, overall survival will be compared betwen the two groups of patients (Uracil <16 vs Uracil ≥16).
Uracil concentration ≥16 ng/mL
Patients were included in this arm if they have digestive cancer and an uracil dosage <16 ng/mL performed between February 2018 to January 2020, and if they received at least one cycle of fluoropyrimidine-based chemotherapy in one of the four oncology departments (Hopital Edouard Heriot [Lyon], Centre Hospitalier de Lyon Sud [Lyon], Hopital de la Croix Rousse [Lyon].
Drug: Fluoropyrimidine treatment (5-FU or capecitabine) and dosage
In each group with an uracil dosage; at cycle 1; capecitabine or continuous 5-FU dose percentage will be evaluate retrospectively in our database
Other: Uracil dosage
For each patient, uracil concentration will be evaluate and patients will be compared based on 16 ng/mL as threshold.
Behavioral: Overall survival
For each group of patient, on 16 ng/mL as threshold for uracil concentration, overall survival will be compared betwen the two groups of patients (Uracil <16 vs Uracil ≥16).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival according to plasma uracil concentration
Time Frame: Last completion date March 30th 2021
Last completion date March 30th 2021

Collaborators and Investigators

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

Sponsor

Hospices Civils de Lyon

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)

November 2, 2020

Primary Completion (Actual)

February 10, 2021

Study Completion (Actual)

April 15, 2021

Study Registration Dates

First Submitted

June 2, 2021

First Submitted That Met QC Criteria

June 2, 2021

First Posted (Actual)

June 8, 2021

Study Record Updates

Last Update Posted (Actual)

June 8, 2021

Last Update Submitted That Met QC Criteria

June 2, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 69HCL21_0489

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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