Exploratory Study of CAPEcitabine pharmacokinetics and hand-foot syndrome in CES1 variant carriers: the ESCAPE study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Jan 2025 → ongoing

Decision date (initial)

2024-10-14

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic, Pharmacogenetic

to demonstrate an increase of 25% in the area under the curve (AUC) 0-6h of 5-FU at the last day of capecitabine administration in cycle 1 between carriers of the CES1 1165–33 C>A (rs2244613) SNP and wild type patients.

Secondary objectives 6

1. to identify differences in AUC of other metabolites of capecitabine in carriers of the CES1 1165–33 C>A der(rs2244613) SNP.
2. to identify differences in dermal and urinary pharmacokinetics of capecitabine and its metabolites in carriers of the CES1 1165–33 C>A (rs2244613) SNP;
3. to analyse the contribution of other SNPs in the metabolic pathway of capecitabine to inter-individual differences in capecitabine pharmacokinetics
4. to study differences in development of toxicity (HFS or other) among carriers vs wildtypes for CES1 1165–33 C>A (rs2244613)
5. to perform an exploratory analysis of endogenous pyrimidine metabolites using metabolomics in order to search for new markers of capecitabine toxicity
6. to study inter-individual differences in the pharmacokinetics of oxaliplatin, in relation with pharmacogenetics and the development of toxicity

Conditions and MedDRA coding

Locally advanced or metastatic gastro-intestinal carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. ≥18 years of age;
2. Planned to start treatment with capecitabine monotherapy or capecitabine-containing combination regimens according to standard of care (irrespective of dose);
3. Fit for treatment with capecitabine as judged by the treating physician;
4. Capable of understanding and complying with protocol requirements and able to understand and sign the informed consent form.

Exclusion criteria 5

1. Carrier of a known clinically relevant DPYD variant (i.e. *2A, *7, *13, c.1236G>A or c.2846A>T);
2. 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.
3. Prior treatment with fluoropyrimidines;
4. Use of DPD-inhibitors and/or allopurinol;
5. Known pregnancy at baseline.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • Difference in AUC0-6 of 5-FU among carriers vs wildtypes for CES1 1165–33 C>A (rs2244613) on C1D14

Secondary endpoints 5

1. Difference in AUC0-6 of capecitabine and its metabolites besides 5-FU (e.g. capecitabine, 5DFCR, 5DFUR, DHFU, FBAL and FAC) among carriers vs wildtypes for CES1 1165–33 C>A (rs2244613) on C1D14
2. Differences in concentrations of 5-FU and other metabolites in dermal biopsies and urine among carriers vs wildtypes for CES1 1165–33 C>A (rs2244613) on C1D14
3. Genotyping of SNPs in genes related to the metabolic pathway of capecitabine (including but not limited to CES1, CES2, CDA, TP, DPYD, DPYS, PPAR-delta), in association with PK and toxicity
4. Incidence of toxicity for the respective subgroups, HFS-14 questionnaire scores
5. Differences in the pharmacokinetics of oxaliplatin, in relation with pharmacogenetics and the development of toxicity using plasm concentrations measured on C1D1 (post-infusion) and on C1D14

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Niels Heersche

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Niels Heersche

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications