Impact of CES1 Genotype on Capecitabine Exposure in Cancer Patients

Recruiting

• Conditions: Solid Cancer; Gastric (Cardia, Body) Cancer; Esophageal Cancer; Colorectal Cancer (CRC)
• Interventions: Drug: Blood sampling for pharmacokinetics

• Registration Number: NCT07114627
• Lead Sponsor: Erasmus Medical Center

Brief Summary

In this study, the drug capecitabine is investigated. Capecitabine is commonly used to treat breast, colon, and stomach cancers. Capecitabine is taken in tablet form. In the body, capecitabine is converted into the active molecule that has anti-cancer effects. This molecule is called 5-FU. The transformation of capecitabine to 5-FU occurs through specific proteins in the liver, also known as enzymes.

Unfortunately, capecitabine can also cause side effects. One of the most common side effects is hand-foot syndrome. In hand-foot syndrome, the palms of the hands and soles of the feet become red and painful. Previous research has shown that patients in whom one of the enzymes responsible for converting capecitabine in the liver does not function properly experience an increase in side effects frequency, particularly severe hand-foot syndrome. This specific enzyme is called CES1. It is believed that side effects occur more frequently because capecitabine is transformed more slowly, eventually leading to a prolonged exposure to 5-FU in the body.

In roughly one in three people, this enzyme functions less efficiently. To gain a better understanding of how this mechanism works, we aim to conduct this study. In this study, we will examine if patients with a less effective CES1 enzyme have higher amounts of 5-FU in their blood. We will also look into whether these patients develop side effects, such as hand-foot syndrome, more frequently. This information could eventually help us develop new strategies to reduce side effects for these patients in the future.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-02-18
• Status Verified: 2025-08
• Study First Submitted: 2025-08-04
• Study First Submitted QC: 2025-08-04
• Last Update Submitted: 2025-08-04
• Study First Posted: 2025-08-11
• Last Update Posted: 2025-08-11
• Primary Completion: 2026-12
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

Not provided

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Carrier of a known clinically relevant DPYD variant (i.e. *2A, *7, *13, c.1236G>A or c.2846A>T);
• 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);
• Prior treatment with fluoropyrimidines;
• Use of DPD-inhibitors and/or allopurinol;
• Known pregnancy at baseline.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Single-nucleotide polymorphism (SNP)	Blood sampling for pharmacokinetics	Oncological patients who are treated with CAPOX (with or without additional anti-neoplastic agents, including but not limited to nivolumab, trastuzumab or bevacizumab) according to standard of care. These patients are known carriers of the CES1 1165-33 C\>A (rs2244613) SNP.
Wild type	Blood sampling for pharmacokinetics	Oncological patients who are treated with CAPOX (with or without additional anti-neoplastic agents, including but not limited to nivolumab, trastuzumab or bevacizumab) according to standard of care. These patients are known carriers of the wild-type CES1 gene.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic Exposure	Up to 6 hours after intake of capecitabine	Difference in Area Under the Curve (AUC)

Trial Locations

Locations (1)

Erasmus MC Cancer Institute; 🇳🇱 Rotterdam, Netherlands