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

Trial Title: Dose Individualization of Chemotherapy in Patients With Gastrointestinal Cancers Lacking a Specific Liver Enzyme

NCT ID: NCT06475352

Condition: Digestive Cancer
Colorectal Cancer

Conditions: Official terms:
Gastrointestinal Neoplasms

Conditions: Keywords:
Fluoropyrimidine
FOLFOX
CAPOX
Adjuvant
Metastatic
Recurrent
Colorectal
digestive
Cancer

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: FOLFOX regimen
Description: 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)
Arm group label: Uracilemia <16
Arm group label: Uracilemia [100-150[
Arm group label: Uracilemia [16-20[
Arm group label: Uracilemia [20-50[ - 25%
Arm group label: Uracilemia [20-50[ - 50%
Arm group label: Uracilemia [50-100[

Intervention type: Drug
Intervention name: CAPOX regimen
Description: 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
Arm group label: Uracilemia <16
Arm group label: Uracilemia [100-150[
Arm group label: Uracilemia [16-20[
Arm group label: Uracilemia [20-50[ - 25%
Arm group label: Uracilemia [20-50[ - 50%
Arm group label: Uracilemia [50-100[

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.

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: October 2024

Completion date: October 2029

Lead sponsor:
Agency: UNICANCER
Agency class: Other

Source: UNICANCER

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06475352