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RecruitingNCT07114627ESCAPEUpdated Aug 11, 2025

Impact of CES1 Genotype on Capecitabine Exposure in Cancer Patients

An observational study in Solid Cancer, Gastric (Cardia, Body) Cancer and Esophageal Cancer, sponsored by Erasmus Medical Center. Recruiting at 1 site in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-08-11.

Sponsored by Erasmus Medical Center · Observational

Study type
Observational
Model
Other
Time perspective
Prospective
Enrollment
66
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Solid Cancer
  • Gastric (Cardia, Body) Cancer
  • Esophageal Cancer
  • Colorectal Cancer (CRC)

Keywords

  • CAPOX
  • CES1
  • carboxylesterase 1
  • Capecitabine
  • Pharmacokinetics
  • Pharmacogenetics
  • Oncology
  • SNP
  • Single-nucleotide polymorphism
  • rs2244613
  • Hand-foot syndrome
  • HFS
  • 5-FU
  • ErasmusMC
  • Cancer
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Sampling method
Probability sample

Study population

Patients with cancer who are intended to start with CAPOX treatment.

Eligibility criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

  • 18 years of age or older;
  • Planned to start treatment with concomitant capecitabine and oxaliplatin according to standard of care (irrespective of dose);
  • Fit for treatment with capecitabine and oxaliplatin as judged by the treating physician;
  • Capable of understanding and complying with protocol requirements and able to understand and sign the informed consent form.

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.
04

Study design

Observational model
Other
Time perspective
Prospective
Enrollment
66 participants (estimated)
Target follow-up
2 Years
Patient registry
Yes
Biospecimen retention
Samples with dna

Groups and cohorts

  • Single-nucleotide polymorphism (SNP)

    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.

    Drug: Blood sampling for pharmacokinetics

  • Wild type

    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.

    Drug: Blood sampling for pharmacokinetics

Interventions

  • DrugBlood sampling for pharmacokinetics

    Extra blood samples are collected for assement of the pharmacokinetics of capecitabine.

05

What researchers measure

Primary outcomes

  1. Pharmacokinetic Exposure

    Difference in Area Under the Curve (AUC)

    Time frame: Up to 6 hours after intake of capecitabine

06

Study locations

1 of 1 sites recruiting
  • Erasmus MC Cancer Institute
    Rotterdam, 3015GD, Netherlands
    Recruiting
07

Registry details

Key details

Study ID
NCT07114627
Lead sponsor
Erasmus Medical Center
Responsible party
Niels Heersche (PI: Sander Bins, Erasmus Medical Center) — Principal investigator
First posted
Aug 11, 2025
Start date
Feb 18, 2025
Primary completion
Dec 2026 (estimated)
Completion
Jun 2027 (estimated)
Last update
Aug 11, 2025

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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