Dose Individualization of Chemotherapy in Patients With Gastrointestinal Cancers Lacking a Specific Liver Enzyme
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUNICANCER
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients with pre-treatment screening based on [U] value according to INCa/HAS recommendations.
Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2
biweekly 5-FU and oxaliplatin (FOLFOX) +/- targeted therapy (TT)
three-weekly capecitabine and oxaliplatin (CAPOX) +/- TT
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
FOLFOX regimen
DrugOxaliplatin 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)
CAPOX regimen
DrugOxaliplatin 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
Treatment groups
400 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: Uracilemia <16Active comparator 2 interventions
Group B: Uracilemia [16-20[Experimental treatment 2 interventions
Group C: Uracilemia [20-50[ - 25%Experimental treatment 2 interventions
Group D: Uracilemia [20-50[ - 50%Experimental treatment 2 interventions
Group E: Uracilemia [50-100[Experimental treatment 2 interventions
Group F: Uracilemia [100-150[Experimental treatment 2 interventions
Trial outcomes
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.
Time frame
Throughout the two first cycles of treatment, up to 42 daysSecondary outcomes
1
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)
Time frame
Throughout the four first cycles of treatment, up to 3 months2
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
Time frame
Throughout the four first cycles of treatment, up to 3 months3
Percentage of fluoropyrimidine dose modification
Percentage of patients for whom fluoropyrimidine dose is increased or decreased
Time frame
Throughout the four first cycles of treatment, up to 3 months4
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.
Time frame
Throughout the four first cycles of treatment, up to 3 months Source ClinicalTrials.gov