Impact of CES1 Genotype on Capecitabine Exposure in Cancer Patients
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Blood sampling for pharmacokinetics.
- Who it may be relevant to
- Registry conditions: Solid Cancer, Gastric (Cardia, Body) Cancer, Esophageal Cancer, Colorectal Cancer (CRC). Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Netherlands
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Exploratory Study of Capecitabine Pharmacokinetics and Hand-foot Syndrome in CES1 Variant Carriers: the ESCAPE Study
Overview
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.
Interventions
- Drug Blood sampling for pharmacokinetics
Extra blood samples are collected for assement of the pharmacokinetics of capecitabine.
Primary outcome measures
- Pharmacokinetic Exposure [Time frame: Up to 6 hours after intake of capecitabine]
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Study design
- Observational model
- Other
Study locations
Netherlands · 1 center
- Erasmus MC Cancer Institute — Rotterdam
Identifiers
NCT: NCT07114627 · MEC 2024-0518 · 2024-516788-96-00