Dose Individualization of Chemotherapy in Patients With Gastrointestinal Cancers Lacking a Specific Liver Enzyme
- Conditions
- Digestive CancerColorectal Cancer
- Interventions
- Drug: FOLFOX regimenDrug: CAPOX regimen
- Registration Number
- NCT06475352
- Lead Sponsor
- UNICANCER
- 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
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 400
-
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.
- 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.
- Participation in another therapeutic trial within 30 days prior to inclusion.
- Persons deprived of their liberty or under protective custody or guardianship.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Uracilemia [20-50[ - 25% FOLFOX regimen Patients with uracilemia between \[20-50\[ ng/mL will be randomized to receive a 25% fluoropyrimidine dose reduction Uracilemia [50-100[ FOLFOX regimen Patients with uracilemia between \[50-100\[ ng/mL will receive a 50% fluoropyrimidine dose reduction Uracilemia [20-50[ - 25% CAPOX regimen Patients with uracilemia between \[20-50\[ ng/mL will be randomized to receive a 25% fluoropyrimidine dose reduction Uracilemia [100-150[ FOLFOX regimen Patients with uracilemia between \[100-150\[ ng/mL will receive a 75% fluoropyrimidine dose reduction Uracilemia <16 FOLFOX regimen Patient with uracilemia \<16 ng/mL will receive a full standard fluoropyrimidine dose Uracilemia [16-20[ FOLFOX regimen Patients with uracilemia between \[16-20\[ ng/mL will receive a full standard fluoropyrimidine dose -dose Uracilemia [20-50[ - 50% CAPOX regimen Patients with uracilemia between \[20-50\[ ng/mL will be randomized to receive a 50% fluoropyrimidine dose reduction Uracilemia [50-100[ CAPOX regimen Patients with uracilemia between \[50-100\[ ng/mL will receive a 50% fluoropyrimidine dose reduction Uracilemia <16 CAPOX regimen Patient with uracilemia \<16 ng/mL will receive a full standard fluoropyrimidine dose Uracilemia [16-20[ CAPOX regimen Patients with uracilemia between \[16-20\[ ng/mL will receive a full standard fluoropyrimidine dose -dose Uracilemia [20-50[ - 50% FOLFOX regimen Patients with uracilemia between \[20-50\[ ng/mL will be randomized to receive a 50% fluoropyrimidine dose reduction Uracilemia [100-150[ CAPOX regimen Patients with uracilemia between \[100-150\[ ng/mL will receive a 75% fluoropyrimidine dose reduction
- Primary Outcome Measures
Name Time Method Proportion of fluoropyrimidine-induced grade ≥ 3 haematological and gastrointestinal toxicity after 2 cycles Throughout the two first cycles of treatment, up to 42 days 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.
- Secondary Outcome Measures
Name Time Method Percentage of fluoropyrimidine dose modification Throughout the four first cycles of treatment, up to 3 months Percentage of patients for whom fluoropyrimidine dose is increased or decreased
Recommended fluoropyrimidine dose Throughout the four first cycles of treatment, up to 3 months 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)
Description of fluoropyrimidine dose Throughout the four first cycles of treatment, up to 3 months 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
Fluoropyrimidine toxicity during the study Throughout the four first cycles of treatment, up to 3 months 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.
Disease-free survival (DFS) - Stage III Colon Cancer 3 years 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.
Overall survival (OS) - Stage III Colon Cancer From randomization to death from any cause, up to 3 years. The overall survival is the length of time from randomization that patients enrolled in the study are still alive.
Progression-free survival (PFS) - Stage IV Colon Cancer From randomization to disease progression or death, up to 1 year. 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.
Trial Locations
- Locations (34)
CHU Amiens
🇫🇷Amiens, France
Institut du Cancer Avignon Provence
🇫🇷Avignon, France
CH Aunay Bayeux
🇫🇷Bayeux, France
CH Cote Basque
🇫🇷Bayonne, France
CHU Besançon
🇫🇷Besançon, France
Centre François Baclesse
🇫🇷Caen, France
Polyclinique du Parc - Centre d'Oncologie Maurice Tubiana
🇫🇷Caen, France
Hopital Privé Drome-Ardeche
🇫🇷Guilherand-Granges, France
CHU Clermont Ferrand
🇫🇷Clermont-Ferrand, France
Hopital Beaujon
🇫🇷Clichy, France
Hopital Henri Mondor
🇫🇷Créteil, France
CHU Dijon
🇫🇷Dijon, France
GH Mutualiste de Grenoble
🇫🇷Grenoble, France
CHU Dupuytren
🇫🇷Limoges, France
Hopital Privé Jean Mermoz
🇫🇷Lyon, France
Centre Léon Bérard
🇫🇷Lyon, France
Grand Hopital de l'Est Francilien
🇫🇷Meaux, France
Hopital Nord Franche Comté - Site du Mittan
🇫🇷Montbéliard, France
Centre Antoine Lacassagne
🇫🇷Nice, France
CHU d'Orléans
🇫🇷Orléans, France
Institut Curie
🇫🇷Paris, France
Hopital Saint Louis
🇫🇷Paris, France
Hopital Saint Antoine
🇫🇷Paris, France
GH Diaconesses Croix St Simon
🇫🇷Paris, France
CHU Bordeaux
🇫🇷Pessac, France
Hospices Civiles de Lyon
🇫🇷Pierre-Bénite, France
CHU Poitiers
🇫🇷Poitiers, France
Hopital Robert Debré
🇫🇷Reims, France
Institut Jean Godinot
🇫🇷Reims, France
CH de Saint Malo
🇫🇷Saint-Malo, France
Institut du Cancer de Strasbourg
🇫🇷Strasbourg, France
CHU de Toulouse
🇫🇷Toulouse, France
Hopital Bretonneau
🇫🇷Tours, France
Gustave Roussy Cancer Campus
🇫🇷Villejuif, France