Dose Individualization of Chemotherapy in Patients With Gastrointestinal Cancers Lacking a Specific Liver Enzyme (FUDOSE)

Dihydropyrimidine Dehydrogenase (DPD) Phenotype-guided Dose Individualization of Fluoropyrimidine-based Chemotherapy in DPD Deficient Patients With Gastrointestinal Cancers

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

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Digestive Cancer
• Intervention / Treatment: Drug: FOLFOX regimen; Drug: CAPOX regimen

Detailed Description

Multicenter phase II trial evaluating different strategies of pre-specified fluoropyrimidine-dose adjustment according to [U] in DPD-deficient patients with gastrointestinal cancer.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Laure MONARD; Phone Number: 01 73 79 73 09; Email: l-monard@unicancer.fr
• Study Contact Backup: Name: Nicolas DE SOUSA CARVALHO; Phone Number: 01 71 93 67 09; Email: n-de-sousa@unicancer.fr

Study Locations

• France
  • Amiens, France, 50054
    • Recruiting
    • CHU Amiens
    • Principal Investigator: Vincent HAUTEFEUILLE, Dr.
  • Aurillac, France
    • Recruiting
    • Hôpital Henri Mondor
    • Principal Investigator: Daniela BURLACU
  • Avignon, France, 84000
    • Recruiting
    • Institut du Cancer Avignon Provence
    • Principal Investigator: Clémence TOULLEC, Dr.
  • Bayeux, France, 14400
    • Recruiting
    • CH Aunay Bayeux
    • Principal Investigator: Annie PEYTIER, Dr.
  • Bayonne, France, 64109
    • Recruiting
    • CH Côte Basque
    • Principal Investigator: Franck AUDEMAR, Dr.
  • Besançon, France, 25000
    • Recruiting
    • CHU Besançon
    • Principal Investigator: Angélique VIENOT, Dr.
  • Caen, France, 14000
    • Recruiting
    • Centre Francois Baclesse
    • Principal Investigator: Stéphane CORBINAIS, Dr.
  • Caen, France, 14000
    • Recruiting
    • Polyclinique du Parc - Centre d'Oncologie Maurice Tubiana
    • Principal Investigator: Maud VILLEMIN, Dr.
  • Caluire-et-Cuire, France
    • Not yet recruiting
    • Infirmerie Protestante
    • Principal Investigator: Emmanuelle GRAILLOT
  • Clermont-Ferrand, France, 63003
    • Not yet recruiting
    • Chu Clermont Ferrand
    • Principal Investigator: Morgane HELYON, Dr.
  • Clichy, France, 92110
    • Recruiting
    • Hopital Beaujon
    • Principal Investigator: Mohamed BOUATTOUR, Dr.
  • Créteil, France, 94010
    • Recruiting
    • Hôpital Henri Mondor
    • Principal Investigator: Charlotte FENIOUX, Dr.
  • Dijon, France, 21079
    • Recruiting
    • CHU Dijon
    • Principal Investigator: Come LEPAGE, Dr.
  • Grenoble, France, 38028
    • Recruiting
    • GH Mutualiste de Grenoble
    • Principal Investigator: Camille HERVE, Dr.
  • Guilherand-Granges, France, 07500
    • Recruiting
    • Hopital Privé Drome-Ardeche
    • Principal Investigator: Agnes PELAQUIER, Dr.
  • Lille, France
    • Recruiting
    • Centre Oscar Lambret
    • Principal Investigator: Aurélien Dr CARNOT
  • Limoges, France, 87042
    • Recruiting
    • Chu Dupuytren
    • Principal Investigator: Frédéric THUILLIER, Dr.
  • Lyon, France, 69373
    • Recruiting
    • Centre Leon Berard
    • Principal Investigator: Clelia COUTZAC, Dr.
  • Lyon, France, 69008
    • Recruiting
    • Hopital Prive Jean Mermoz
    • Principal Investigator: Jérome DESRAME, Dr.
  • Meaux, France, 77100
    • Recruiting
    • Grand Hôpital de l'Est Francilien
    • Principal Investigator: Christophe LOCHER, Dr
  • Montbéliard, France, 25200
    • Recruiting
    • Hopital Nord Franche Comté - Site du Mittan
    • Principal Investigator: Christophe BORG, Dr.
  • Nice, France, 06189
    • Recruiting
    • Centre Antoine Lacassagne
    • Principal Investigator: Claire JARAUDIAS, Dr.
  • Orléans, France, 45067
    • Recruiting
    • CHU d'Orléans
    • Principal Investigator: Jean-Paul LAGASSE, Dr.
  • Paris, France, 75010
    • Recruiting
    • Hopital Saint Louis
    • Principal Investigator: Thomas APARICIO, Pr.
  • Paris, France, 75005
    • Recruiting
    • Institut Curie
    • Principal Investigator: Pauline VAFLARD, Dr.
  • Paris, France
    • Recruiting
    • Hôpital Européen Georges Pompidou
    • Principal Investigator: Aziz Pr ZAANAN
  • Paris, France, 75012
    • Recruiting
    • Hôpital Saint Antoine
    • Principal Investigator: Daniel LOPEZ TRABADA ATAZ, Dr.
  • Paris, France, 75020
    • Recruiting
    • GH Diaconesses Croix St Simon
    • Principal Investigator: Olivier DUBREUIL, Dr.
  • Pessac, France, 33600
    • Recruiting
    • CHU Bordeaux
    • Principal Investigator: Denis SMITH, Dr.
  • Pierre-Bénite, France, 69495
    • Recruiting
    • Hospices Civiles de Lyon
    • Principal Investigator: Marion CHAUVENET, Dr.
  • Poitiers, France, 86000
    • Recruiting
    • CHU Poitiers
    • Principal Investigator: David TOUGERON, Pr.
  • Reims, France, 51100
    • Withdrawn
    • Institut Jean Godinot
  • Reims, France, 51100
    • Recruiting
    • Hôpital Robert Debré
    • Principal Investigator: Olivier BOUCHE, Pr.
  • Rennes, France
    • Not yet recruiting
    • Centre Eugene Marquis
    • Principal Investigator: Astrid LIEVRE
  • Rouen, France
    • Recruiting
    • CHU Rouen - Hopital Charles Nicoles
    • Principal Investigator: Adrien Dr GRANCHER
  • St-Malo, France, 35403
    • Recruiting
    • CH de Saint Malo
    • Principal Investigator: Anne-Sophie MOUSSADDAQ, Dr.
  • Strasbourg, France, 67033
    • Recruiting
    • Institut du Cancer de Strasbourg
    • Principal Investigator: Meher BEN ABDELGHANI, Dr.
  • Toulouse, France, 31059
    • Recruiting
    • CHU de Toulouse
    • Principal Investigator: Nadim FARES, Dr.
  • Tours, France, 37044
    • Recruiting
    • Hopital Bretonneau
    • Principal Investigator: Thierry LECOMTE, Pr.
  • Vandœuvre-lès-Nancy, France
    • Not yet recruiting
    • CHRU Nancy
    • Principal Investigator: Marie MULLER
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy Cancer Campus
    • Principal Investigator: Valérie BOIGE, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with pre-treatment screening based on [U] value according to INCa/HAS recommendations.
2. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2

3. 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
4. Age ≥ 18 years
5. Patients eligible for full standard fluoropyrimidine and oxaliplatin doses regardless of DPD deficiency
6. 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
7. 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.
8. Women of childbearing potential must have a negative serum or urine pregnancy test.
9. 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.
10. Patients must be affiliated to a Social Security System (or equivalent).
11. 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.

Exclusion Criteria:

1. Patients with complete DPD deficiency based on [U] ≥150 ng/mL
2. Any prior treatment including a fluoropyrimidine
3. Patients with any contraindication to treatment with fluoropyrimidine or oxaliplatin regardless of DPD deficiency
4. Patients not eligible for full standard dose fluoropyrimidine and oxaliplatin for clinical reasons including older age and/or comorbidity regardless of a DPD deficiency
5. 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
6. Recent or concomitant treatment with brivudine
7. Pregnant or breastfeeding woman.
8. Participation in another therapeutic trial within 30 days prior to inclusion.
9. Persons deprived of their liberty or under protective custody or guardianship.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Uracilemia <16; Patient with uracilemia <16 ng/mL will receive a full standard fluoropyrimidine dose	Drug: FOLFOX regimen; 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); Drug: CAPOX regimen; 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
Experimental: Uracilemia [16-20[; Patients with uracilemia between [16-20[ ng/mL will receive a full standard fluoropyrimidine dose -dose	Drug: FOLFOX regimen; 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); Drug: CAPOX regimen; 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
Experimental: Uracilemia [20-50[ - 25%; Patients with uracilemia between [20-50[ ng/mL will be randomized to receive a 25% fluoropyrimidine dose reduction	Drug: FOLFOX regimen; 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); Drug: CAPOX regimen; 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
Experimental: Uracilemia [20-50[ - 50%; Patients with uracilemia between [20-50[ ng/mL will be randomized to receive a 50% fluoropyrimidine dose reduction	Drug: FOLFOX regimen; 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); Drug: CAPOX regimen; 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
Experimental: Uracilemia [50-100[; Patients with uracilemia between [50-100[ ng/mL will receive a 50% fluoropyrimidine dose reduction	Drug: FOLFOX regimen; 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); Drug: CAPOX regimen; 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
Experimental: Uracilemia [100-150[; Patients with uracilemia between [100-150[ ng/mL will receive a 75% fluoropyrimidine dose reduction	Drug: FOLFOX regimen; 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); Drug: CAPOX regimen; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended fluoropyrimidine dose	The rate of fluoropyrimidine induced grade ≥ 3 haematological and gastrointestinal toxicity in each uracilemia-based group of DPD-deficient patients (according to uracilemia level) compared to the rate observed in non DPD-deficient patients (control arm)	Throughout the four first cycles of treatment, up to 3 months
Description of fluoropyrimidine dose	The cumulative dose (mg/m²) of chemotherapy delivered to patients will be recorded along with reasons of dose-modifications or treatment discontinuation for limiting toxicity	Throughout the four first cycles of treatment, up to 3 months
Percentage of fluoropyrimidine dose modification	Percentage of patients for whom fluoropyrimidine dose is increased or decreased	Throughout the four first cycles of treatment, up to 3 months
Fluoropyrimidine toxicity during the study	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 four first cycles of treatment, up to 3 months
Disease-free survival (DFS) - Stage III Colon Cancer	Disease-free survival is defined as the delay between date of inclusion and tumor relapse (local, regional, or distant) or death from any cause, whichever occurs first.	3 years
Overall survival (OS) - Stage III Colon Cancer	The overall survival is the length of time from randomization that patients enrolled in the study are still alive.	From randomization to death from any cause, up to 3 years.
Progression-free survival (PFS) - Stage IV Colon Cancer	The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.	From randomization to disease progression or death, up to 1 year.

Collaborators and Investigators

• Sponsor: UNICANCER
• Investigators: Principal Investigator: Valérie BOIGE, MD, Gustave Roussy Cancer Campus; Study Director: Marie-Anne LORIOT, Hôpital Européen Georges Pompidou

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: June 20, 2024
• First Posted (Actual): June 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; Metastatic; Adjuvant; FOLFOX; Recurrent; Fluoropyrimidine; Colorectal; CAPOX; digestive
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Disease Attributes; Intestinal Diseases; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms; Recurrence; Colorectal Neoplasms; Neoplasm Metastasis; Gastrointestinal Neoplasms; Folfox protocol; XELOX
• Other Study ID Numbers: UC-GIG-2311; 2023-509963-25-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No