Clinical trial NCT06475352: Dose Individualization of Chemotherapy in Patients With Gastrointestinal Cancers Lacking a Specific Liver Enzyme
Official title: Dihydropyrimidine Dehydrogenase (DPD) Phenotype-guided Dose Individualization of Fluoropyrimidine-based Chemotherapy in DPD Deficient Patients With Gastrointestinal Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Digestive Cancer
Colorectal Cancer
Keywords: Fluoropyrimidine
FOLFOX
CAPOX
Adjuvant
Metastatic
Recurrent
Colorectal
digestive
Cancer
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2024-06-26
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Proportion of fluoropyrimidine-induced grade ≥ 3 haematological and gastrointestinal toxicity after 2 cycles
timeFrame: Throughout the two first cycles of treatment, up to 42 days
Secondary outcomes:
measure: Recommended fluoropyrimidine dose
timeFrame: Throughout the four first cycles of treatment, up to 3 months
measure: Description of fluoropyrimidine dose
timeFrame: Throughout the four first cycles of treatment, up to 3 months
measure: Percentage of fluoropyrimidine dose modification
timeFrame: Throughout the four first cycles of treatment, up to 3 months
measure: Fluoropyrimidine toxicity during the study
timeFrame: Throughout the four first cycles of treatment, up to 3 months
measure: Disease-free survival (DFS) - Stage III Colon Cancer
timeFrame: 3 years
measure: Overall survival (OS) - Stage III Colon Cancer
timeFrame: From randomization to death from any cause, up to 3 years.
measure: Progression-free survival (PFS) - Stage IV Colon Cancer
timeFrame: From randomization to disease progression or death, up to 1 year.
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Avignon
country: France
facility: Institut du Cancer Avignon Provence
city: Bayeux
country: France
facility: CH Aunay Bayeux
city: Bayonne
country: France
facility: CH Cote Basque
city: Besançon
country: France
facility: CHU Besançon
city: Caen
country: France
facility: Centre François Baclesse
city: Caen
country: France
facility: Polyclinique du Parc - Centre d'Oncologie Maurice Tubiana
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand
city: Clichy
country: France
facility: Hopital Beaujon
city: Créteil
country: France
facility: Hopital Henri Mondor
city: Dijon
country: France
facility: CHU Dijon
city: Grenoble
country: France
facility: GH Mutualiste de Grenoble
city: Guilherand-Granges
country: France
facility: Hopital Privé Drome-Ardeche
city: Limoges
country: France
facility: CHU Dupuytren
city: Lyon
country: France
facility: Hopital Privé Jean Mermoz
city: Lyon
country: France
facility: Centre Léon Bérard
city: Meaux
country: France
facility: Grand Hopital de l'Est Francilien
city: Montbéliard
country: France
facility: Hopital Nord Franche Comté - Site du Mittan
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Orléans
country: France
facility: CHU d'Orléans
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: GH Diaconesses Croix St Simon
city: Pessac
country: France
facility: CHU Bordeaux
city: Pierre-Bénite
country: France
facility: Hospices Civiles de Lyon
city: Poitiers
country: France
facility: CHU Poitiers
city: Reims
country: France
facility: Hopital Robert Debré
city: Reims
country: France
facility: Institut Jean Godinot
city: Saint-Malo
country: France
facility: CH de Saint Malo
city: Strasbourg
country: France
facility: Institut du Cancer de Strasbourg
city: Toulouse
country: France
facility: CHU de Toulouse
city: Tours
country: France
facility: Hopital Bretonneau
city: Villejuif
country: France
facility: Gustave Roussy Cancer Campus
Study officials:
affiliation: Gustave Roussy Cancer Campus
name: Valérie BOIGE, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Europeen Georges Pompidou
name: Marie-Anne LORIOT
role: STUDY_DIRECTOR
References: