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NCT Number: NCT06475352

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

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

Recruiting

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Key information

Conditions

Digestive Cancer Colonic Diseases Colorectal Cancer Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Disease Attributes Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasm Metastasis Neoplasms Neoplasms by Site Neoplastic Processes Pathologic Processes Pathological Conditions, Signs and Symptoms Rectal Diseases Recurrence

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

CHU Amiens, Amiens, France

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

FOLFOX regimen

Drug

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)

CAPOX regimen

Drug

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

Primary outcomes

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

    Time frame: 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 outcomes

  1. Recommended fluoropyrimidine dose

    Time frame: 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)

  2. Description of fluoropyrimidine dose

    Time frame: 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

  3. Percentage of fluoropyrimidine dose modification

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

    Percentage of patients for whom fluoropyrimidine dose is increased or decreased

  4. Fluoropyrimidine toxicity during the study

    Time frame: 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.

  5. Disease-free survival (DFS) - Stage III Colon Cancer

    Time frame: 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.

  6. Overall survival (OS) - Stage III Colon Cancer

    Time frame: 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.

  7. Progression-free survival (PFS) - Stage IV Colon Cancer

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Laure MONARD

CONTACT

[email protected]

01 73 79 73 09

Nicolas DE SOUSA CARVALHO

CONTACT

[email protected]

01 71 93 67 09

Sponsors and collaborators

Lead sponsor

UNICANCER

Other

Registry information

Official study title

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

Acronym: FUDOSE

Important dates

Study start
2025
Primary completion
2027
Study completion
2030
First posted
Jun 26, 2024
Registry last updated
Apr 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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