Capecitabine for Locally advanced or metastatic gastrointestinal carcinoma

Inclusion criteria

• {"criterion_text":"- ≥18 years of age;\n- Planned to start treatment with capecitabine monotherapy or capecitabine-containing combination regimens according to standard of care (irrespective of dose);\n- Fit for treatment with capecitabine as judged by the treating physician;\n- Capable of understanding and complying with protocol requirements and able to understand and sign the informed consent form."}

Exclusion criteria

• {"criterion_text":"- Carrier of a known clinically relevant DPYD variant (i.e. *2A, *7, *13, c.1236G>A or c.2846A>T);\n- Any medical condition that is known to influence capecitabine absorption (i.e. a Roux-en-Y gastric bypass operation or complete gastric resection; an esophagectomy is not considered to impair absorption); •\tPrior treatment with fluoropyrimidines; •\tUse of DPD-inhibitors and/or allopurinol; •\tKnown pregnancy at baseline.\n- Prior treatment with fluoropyrimidines;\n- Use of DPD-inhibitors and/or allopurinol;\n- Known pregnancy at baseline."}

Primary endpoints

• {"endpoint_text":"- •\tDifference in AUC0-6 of 5-FU among carriers vs wildtypes for CES1 1165–33 C>A (rs2244613) on C1D14","definition_or_measurement_approach":"AUC0-6 of 5-FU measured in plasma on Cycle 1 Day 14 (pharmacokinetic sampling) to compare carriers of CES1 1165–33 C>A (rs2244613) versus wildtype patients."}

Secondary endpoints

• {"endpoint_text":"- Difference in AUC0-6 of capecitabine and its metabolites besides 5-FU (e.g. capecitabine, 5DFCR, 5DFUR, DHFU, FBAL and FAC) among carriers vs wildtypes for CES1 1165–33 C>A (rs2244613) on C1D14","definition_or_measurement_approach":"AUC0-6 of capecitabine and listed metabolites measured in plasma on Cycle 1 Day 14."}
• {"endpoint_text":"- Differences in concentrations of 5-FU and other metabolites in dermal biopsies and urine among carriers vs wildtypes for CES1 1165–33 C>A (rs2244613) on C1D14","definition_or_measurement_approach":"Concentrations of 5-FU and metabolites measured in dermal biopsy samples and urine collected on Cycle 1 Day 14."}
• {"endpoint_text":"- Genotyping of SNPs in genes related to the metabolic pathway of capecitabine (including but not limited to CES1, CES2, CDA, TP, DPYD, DPYS, PPAR-delta), in association with PK and toxicity","definition_or_measurement_approach":"Genotyping of listed SNPs and association analyses with pharmacokinetic measurements and recorded toxicity."}
• {"endpoint_text":"- Incidence of toxicity for the respective subgroups, HFS-14 questionnaire scores","definition_or_measurement_approach":"Incidence of adverse events/toxicity recorded and HFS-14 questionnaire scores collected to compare subgroups."}
• {"endpoint_text":"- Differences in the pharmacokinetics of oxaliplatin, in relation with pharmacogenetics and the development of toxicity using plasm concentrations measured on C1D1 (post-infusion) and on C1D14","definition_or_measurement_approach":"Plasma concentrations of oxaliplatin measured post-infusion on Cycle 1 Day 1 and on Cycle 1 Day 14; correlated with pharmacogenetic data and toxicity."}

Netherlands

Earliest CTIS Part Ii Submission Date

30-09-2024

Latest Decision Or Authorization Date

15-12-2025

Processing Time Days

441

Number Of Sites

1

Number Of Participants

66

Primary sponsor

Full Name

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands