How the CES1 liver enzyme affects capecitabine levels in people with colorectal, gastric, or esophageal cancer

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

This project will see if differences in the CES1 enzyme change how capecitabine is processed and whether that affects side effects like hand‑foot syndrome in adults starting capecitabine with oxaliplatin for colorectal, gastric, or esophageal cancer.

Quick facts

• Study type: Observational
• Enrollment: 66 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Erasmus Medical Center (Academic / other)
• Locations: 1 site (Rotterdam)
• Trial ID: NCT07114627 on ClinicalTrials.gov

What this trial studies

This is an observational study enrolling adults beginning standard capecitabine plus oxaliplatin (CAPOX) to collect blood samples for pharmacokinetic analysis and CES1 genotyping. Researchers will measure capecitabine exposure and its metabolites over time and correlate those levels with CES1 genetic variants. Patients with known clinically relevant DPYD variants or prior fluoropyrimidine treatment are excluded to avoid confounding. The goal is to link CES1 genotype with drug exposure and frequency of toxicities such as hand‑foot syndrome.

Who should consider this trial

Good fit: Adults (≥18 years) with colorectal, gastric, or esophageal cancer who are planned to start capecitabine plus oxaliplatin, are judged fit for that treatment, and can give informed consent.

Not a fit: Patients who already carry known clinically relevant DPYD variants, have had prior fluoropyrimidine therapy, have surgeries that severely alter capecitabine absorption, or are not receiving capecitabine plus oxaliplatin are unlikely to benefit from this study's findings.

Why it matters

Potential benefit: If successful, clinicians could use CES1 genetic testing to personalize capecitabine dosing and reduce harmful side effects like hand‑foot syndrome.

How similar studies have performed: Variants in other metabolizing enzymes such as DPYD are known to affect fluoropyrimidine toxicity, while CES1's specific impact on capecitabine exposure has some preliminary evidence but remains less well established.

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.

Where this trial is running

Rotterdam

• Erasmus MC Cancer Institute — Rotterdam, Netherlands (Recruiting)

Conditions Solid Cancer; Gastric Cancer; Esophageal Cancer; Colorectal Cancer; CAPOX; CES1; carboxylesterase 1; Capecitabine