Impact of CES1 Genotype on Capecitabine Exposure in Cancer Patients

NCT07114627 | Recruiting FDA Drug

• 2 other identifiers: MEC 2024-05182024-516788-96-00
• Study Type: observational
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic Exposure

  Difference in Area Under the Curve (AUC)

  Up to 6 hours after intake of capecitabine

Study Arms (2)

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

Blood sampling for pharmacokinetics DRUG

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

Single-nucleotide polymorphism (SNP); Wild type

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus MC Cancer Institute

Rotterdam, 3015GD, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

* Blood * Plasma * Urine Optional (additional consent required): \- Skin biopt

MeSH Terms

Conditions

Neoplasms; Esophageal Neoplasms; Colorectal Neoplasms; Hand-Foot Syndrome

Interventions

Blood Specimen Collection; Pharmacokinetics

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Drug Eruptions; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Metabolism; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI: Sander Bins

Study Record Dates

• First Submitted: August 4, 2025
• First Posted: August 11, 2025
• Study Start: February 18, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: August 11, 2025

Record last verified: 2025-08

Locations

NL (1)