Colorectal carcinoma
Conditions
Interventions
The patients will use capecitabine in combination with 40 mg esomeprazole q.d. oral for four consecutive days (phase A and C) or capecitabine alone (phase B), while during phase C capecitabine is take
Sponsors
ErasmusMC Cancer Institute
Eligibility
Inclusion criteria
Inclusion criteria: - Age ≥ 18 years. - Histologically or cytologically confirmed diagnosis of colorectal carcinoma for which capecitabine is an appropriate treatment option. - Planned treatment with capecitabine. - ECOG Performance Status ≤2 (see Appendix B). - Able and willing to sign the informed consent form prior to screening evaluations. -No concurrent (over the counter) use of other acid reducing drugs (PPIs, H2As and/or antacids) other than esomeprazole 40 mg once daily during the study. - Abstain from acid beverage (on study days, except for the Coca-Cola in Phase C according to study procedures), grapefruit, grapefruit juice, grapefruit-related citrus fruits, herbal dietary supplements and herbal tea during the study period.
Exclusion criteria
Exclusion criteria: - Prior treatment with capecitabine is allowed, however, patients with a documented history of ≥ grade 3 toxicities with capecitabine are excluded. - Patients with known impaired drug absorption (e.g. gastrectomy and achlorhydria) - Known serious illness (e.g. patients with oral or insulin-dependent diabetes mellitus) or medical unstable conditions that could interfere with the study medication/liquid. - Patients who are clinical dependent of use of PPIs or other acid reducing drugs. - Known complete deficiency of dihydropyrimidine dehydrogenase (DPD) activity. - Known poor metabolizers of cytochrome P450 2C19. - Use of cytochrome P450 2C19/ 3A4 inducers and or inhibitors. - Use of medicines/supplements wich can interact by capecitabine or esomeprazole.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| A relative difference in the AUC of at least 25% is considered to be clinically relevant (i.e. ratio of geometric means ≤0.75 or ≥1.33) and the within-patient standard deviation is assumed to be 27% | — |
Secondary
| Measure | Time frame |
|---|---|
| - to study other PK parameters, including the clearance (CL), the maximum concentration (Cmax), and time of Cmax (tmax) of capecitabine. - to determine AUC, CL, Cmax and tmax of the metabolites of capecitabine: 5'-deoxy-5-fluorocytidine (5’-DFCR), 5'-deoxy-5-fluorouridine (5’-DFUR) and 5-FU. - to evaluate the incidence and severity of side- effects of treatment with capecitabine in the presence of esomeprazole alone and in the presence of esomeprazole combined with the acid beverage Coca-Cola Classic. | — |
Contacts
Public ContactL. (Leni) Doorn, van
Outcome results
None listed