NCT06475352

Brief Summary

The goal of this clinical trial is to establish guidelines for fluoropyrimidine dose reduction according to uracilemia in patients with DPD deficiency in the treatment of digestive cancers. The main question it aims to answer is: \- Which reduction dose of fluoropyrimidine is needed for patient with DPD deficiency? Participants will:

  • Take the treatment with the reduction of dose stated by the protocol
  • Visit the clinic once every 2-3 weeks for checkups and tests for collection of adverse events

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
400

participants targeted

Target at P75+ for phase_2

Timeline
44mo left

Started Jan 2025

Longer than P75 for phase_2

Geographic Reach
1 country

41 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress26%
Jan 2025Jan 2030

First Submitted

Initial submission to the registry

June 20, 2024

Completed
6 days until next milestone

First Posted

Study publicly available on registry

June 26, 2024

Completed
7 months until next milestone

Study Start

First participant enrolled

January 20, 2025

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2027

Expected
2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2030

Last Updated

April 23, 2026

Status Verified

March 1, 2026

Enrollment Period

2.2 years

First QC Date

June 20, 2024

Last Update Submit

April 22, 2026

Conditions

Digestive CancerColorectal Cancer

Keywords

FluoropyrimidineFOLFOXCAPOXAdjuvantMetastaticRecurrentColorectaldigestiveCancer

Outcome Measures

Primary Outcomes (1)

  • Proportion of fluoropyrimidine-induced grade ≥ 3 haematological and gastrointestinal toxicity after 2 cycles

    The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.

    Throughout the two first cycles of treatment, up to 42 days

Secondary Outcomes (7)

  • Recommended fluoropyrimidine dose

    Throughout the four first cycles of treatment, up to 3 months

  • Description of fluoropyrimidine dose

    Throughout the four first cycles of treatment, up to 3 months

  • Percentage of fluoropyrimidine dose modification

    Throughout the four first cycles of treatment, up to 3 months

  • Fluoropyrimidine toxicity during the study

    Throughout the four first cycles of treatment, up to 3 months

  • Disease-free survival (DFS) - Stage III Colon Cancer

    3 years

  • +2 more secondary outcomes

Study Arms (6)

Uracilemia <16

ACTIVE COMPARATOR

Patient with uracilemia \<16 ng/mL will receive a full standard fluoropyrimidine dose

Drug: FOLFOX regimenDrug: CAPOX regimen

Uracilemia [16-20[

EXPERIMENTAL

Patients with uracilemia between \[16-20\[ ng/mL will receive a full standard fluoropyrimidine dose -dose

Drug: FOLFOX regimenDrug: CAPOX regimen

Uracilemia [20-50[ - 25%

EXPERIMENTAL

Patients with uracilemia between \[20-50\[ ng/mL will be randomized to receive a 25% fluoropyrimidine dose reduction

Drug: FOLFOX regimenDrug: CAPOX regimen

Uracilemia [20-50[ - 50%

EXPERIMENTAL

Patients with uracilemia between \[20-50\[ ng/mL will be randomized to receive a 50% fluoropyrimidine dose reduction

Drug: FOLFOX regimenDrug: CAPOX regimen

Uracilemia [50-100[

EXPERIMENTAL

Patients with uracilemia between \[50-100\[ ng/mL will receive a 50% fluoropyrimidine dose reduction

Drug: FOLFOX regimenDrug: CAPOX regimen

Uracilemia [100-150[

EXPERIMENTAL

Patients with uracilemia between \[100-150\[ ng/mL will receive a 75% fluoropyrimidine dose reduction

Drug: FOLFOX regimenDrug: CAPOX regimen

Interventions

FOLFOX regimenDRUG

Oxaliplatin will be administered at a fixed dose of 85 mg/m² by 2h intravenous (IV) infusion concurrently with folinic acid 400 mg/m² (or 200 mg/m² if L-folinic acid) as a 2 h IV infusion on day 1 of each 14-day cycle followed by 5-fluorouracil (5-FU) 400 mg/m² IV bolus on day 1, then continuous IV infusion of 1,200 mg/m² /day × 2 days (total 2400 mg/m² for 46-48 hours)

Uracilemia <16Uracilemia [100-150[Uracilemia [16-20[Uracilemia [20-50[ - 25%Uracilemia [20-50[ - 50%Uracilemia [50-100[
CAPOX regimenDRUG

Oxaliplatin will be administered at a fixed dose of 130 mg/m² by 2h IV infusion on day 1 of each 21-day cycle followed by capecitabine (1000 mg/m²) twice a day (BID) during 2 weeks, every 3 weeks

Uracilemia <16Uracilemia [100-150[Uracilemia [16-20[Uracilemia [20-50[ - 25%Uracilemia [20-50[ - 50%Uracilemia [50-100[

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with pre-treatment screening based on \[U\] value according to INCa/HAS recommendations.
  • Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2
  • Fluoropyrimidine-naïve patients with gastrointestinal cancer starting chemotherapy combining fluoropyrimidine (5-FU or capecitabine) and oxaliplatin whatever the context (adjuvant, neoadjuvant, palliative) including the following regimens (the most frequently prescribed in gastrointestinal cancers):
  • biweekly 5-FU and oxaliplatin (FOLFOX) +/- targeted therapy (TT)
  • three-weekly capecitabine and oxaliplatin (CAPOX) +/- TT
  • Age ≥ 18 years
  • Patients eligible for full standard fluoropyrimidine and oxaliplatin doses regardless of DPD deficiency
  • Adequate bone marrow function (cell blood count (CBC)), estimated glomerular filtration rate (DFG) ≥ 50 ml/min, alkaline phosphatase (ALP) / aspartate aminotransferase (ASAT) / alanine aminotransferase (ALAT) ≤ 5 upper limit of normal (ULN), and bilirubin ≤ 50 micromol/L
  • Patient must have signed and dated a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
  • Women of childbearing potential must have a negative serum or urine pregnancy test.
  • Patients must agree to remain abstinent or use contraceptive methods with a failure rate of \< 1% per year for the duration of study treatment and within 6 months after completing treatment.
  • Patients must be affiliated to a Social Security System (or equivalent).
  • Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.

You may not qualify if:

  • Patients with complete DPD deficiency based on \[U\] ≥150 ng/mL
  • Any prior treatment including a fluoropyrimidine
  • Patients with any contraindication to treatment with fluoropyrimidine or oxaliplatin regardless of DPD deficiency
  • Patients not eligible for full standard dose fluoropyrimidine and oxaliplatin for clinical reasons including older age and/or comorbidity regardless of a DPD deficiency
  • Patients unwilling or unable to comply with trial obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the trial
  • Recent or concomitant treatment with brivudine
  • Pregnant or breastfeeding woman.
  • Persons deprived of their liberty or under protective custody or guardianship.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (41)

CHU Amiens

Amiens, 50054, France

RECRUITING

Hopital Henri Mondor

Aurillac, France

RECRUITING

Institut du Cancer Avignon Provence

Avignon, 84000, France

RECRUITING

CH Aunay Bayeux

Bayeux, 14400, France

RECRUITING

CH Cote Basque

Bayonne, 64109, France

RECRUITING

CHU Besançon

Besançon, 25000, France

RECRUITING

Centre François Baclesse

Caen, 14000, France

RECRUITING

Polyclinique du Parc - Centre d'Oncologie Maurice Tubiana

Caen, 14000, France

RECRUITING

Infirmerie Protestante

Caluire-et-Cuire, France

NOT YET RECRUITING

CHU Clermont Ferrand

Clermont-Ferrand, 63003, France

NOT YET RECRUITING

Hopital Beaujon

Clichy, 92110, France

RECRUITING

Hopital Henri Mondor

Créteil, 94010, France

RECRUITING

CHU Dijon

Dijon, 21079, France

RECRUITING

GH Mutualiste de Grenoble

Grenoble, 38028, France

RECRUITING

Hopital Privé Drome-Ardeche

Guilherand-Granges, 07500, France

RECRUITING

Centre Oscar Lambret

Lille, France

RECRUITING

CHU Dupuytren

Limoges, 87042, France

RECRUITING

Hopital Privé Jean Mermoz

Lyon, 69008, France

RECRUITING

Centre Léon Bérard

Lyon, 69373, France

RECRUITING

Grand Hopital de l'Est Francilien

Meaux, 77100, France

RECRUITING

Hopital Nord Franche Comté - Site du Mittan

Montbéliard, 25200, France

RECRUITING

Centre Antoine Lacassagne

Nice, 06189, France

RECRUITING

CHU d'Orléans

Orléans, 45067, France

RECRUITING

Institut Curie

Paris, 75005, France

RECRUITING

Hopital Saint Louis

Paris, 75010, France

RECRUITING

Hopital Saint Antoine

Paris, 75012, France

RECRUITING

GH Diaconesses Croix St Simon

Paris, 75020, France

RECRUITING

Hopital Européen Georges Pompidou

Paris, France

RECRUITING

CHU Bordeaux

Pessac, 33600, France

RECRUITING

Hospices Civiles de Lyon

Pierre-Bénite, 69495, France

RECRUITING

CHU Poitiers

Poitiers, 86000, France

RECRUITING

Hopital Robert Debré

Reims, 51100, France

RECRUITING

Institut Jean Godinot

Reims, 51100, France

WITHDRAWN

Centre Eugene Marquis

Rennes, France

NOT YET RECRUITING

CHU Rouen - Hopital Charles Nicoles

Rouen, France

RECRUITING

CH de Saint Malo

St-Malo, 35403, France

RECRUITING

Institut du Cancer de Strasbourg

Strasbourg, 67033, France

RECRUITING

CHU de Toulouse

Toulouse, 31059, France

RECRUITING

Hopital Bretonneau

Tours, 37044, France

RECRUITING

CHRU Nancy

Vandœuvre-lès-Nancy, France

NOT YET RECRUITING

Gustave Roussy Cancer Campus

Villejuif, 94805, France

RECRUITING

MeSH Terms

Conditions

Gastrointestinal NeoplasmsColorectal NeoplasmsNeoplasm MetastasisRecurrenceNeoplasms

Interventions

Folfox protocolXELOX

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesGastrointestinal DiseasesIntestinal NeoplasmsColonic DiseasesIntestinal DiseasesRectal DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and SymptomsDisease Attributes

Study Officials

  • Valérie BOIGE, MD

    Gustave Roussy Cancer Campus

    PRINCIPAL INVESTIGATOR

  • Marie-Anne LORIOT

    Hopital Europeen Georges Pompidou

    STUDY DIRECTOR

Central Study Contacts

Nicolas DE SOUSA CARVALHO

CONTACT

01 71 93 67 09n-de-sousa@unicancer.fr

Laure MONARD

CONTACT

01 73 79 73 09l-monard@unicancer.fr

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 20, 2024

First Posted

June 26, 2024

Study Start

January 20, 2025

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

January 1, 2030

Last Updated

April 23, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

Locations

FR(41)