Impact of CES1 Genotype on Capecitabine Exposure in Cancer Patients

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.

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Key information

Conditions

Solid Cancer Chemically-Induced Disorders Colonic Diseases Colorectal Cancer (CRC) Colorectal Neoplasms Dermatitis Digestive System Diseases Digestive System Neoplasms Drug Eruptions Drug Hypersensitivity Drug-Related Side Effects and Adverse Reactions Esophageal Cancer Esophageal Diseases Esophageal Neoplasms Gastric (Cardia, Body) Cancer Gastrointestinal Diseases Gastrointestinal Neoplasms Hand-Foot Syndrome Head and Neck Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Erasmus MC Cancer Institute

Rotterdam, 3015GD, Netherlands

Location status: Recruiting

Location contact

N. Heersche

CONTACT

[email protected]

0031 10 7040704

Who can participate

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

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.

Treatment and study plan

Blood sampling for pharmacokinetics

Drug

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

Primary outcomes

Pharmacokinetic Exposure

Time frame: Up to 6 hours after intake of capecitabine

Difference in Area Under the Curve (AUC)

Sponsors and collaborators

Lead sponsor

Erasmus Medical Center

Other

Registry information

Official study title

Exploratory Study of Capecitabine Pharmacokinetics and Hand-foot Syndrome in CES1 Variant Carriers: the ESCAPE Study

Acronym: ESCAPE

Important dates

Study start: 2025
Primary completion: 2026
Study completion: 2027
First posted: Aug 11, 2025
Registry last updated: Aug 11, 2025

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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