|- candidate number||28562|
|- NTR Number||NTR7027|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||9-feb-2018|
|- Secondary IDs||MEC 17-552 NL63906.078.17|
|- Public Title||COCA study|
|- Scientific Title||The effects of the proton pump inhibitor esomeprazole alone or in combination with Coca-Cola on the absorption of Capecitabine in patients with colorectal cancer.
|- hypothesis||To determine the influence of the PPI esomeprazole on the absorption of capecitabine and the impact of the PPI in combination with the acid beverage Coca-Cola on the absorption of capecitabine because PPIs may profoundly decrease solubility and negatively affect the bioavailability of capecitabine by raising gastric pH levels, leading to altered dissolution and absorption of capecitabine.|
|- Healt Condition(s) or Problem(s) studied||Colorectal cancer, PPI, Proton pump inhibitor|
|- 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||- 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.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||7-feb-2018|
|- planned closingdate||1-sep-2020|
|- Target number of participants||22|
|- 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 taken concomitantly with 250 ml Coca Cola. T|
|- Primary outcome||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 outcome||- 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.
|- Timepoints||Pharmacokinetics will be taken at day 5-8 of 3 subsequent cycles.|
|- Trial web site|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||MSc L. (Leni) Doorn, van|
|- CONTACT for SCIENTIFIC QUERIES||MSc L. (Leni) Doorn, van|
|- Sponsor/Initiator ||Erasmus MC - Cancer Institute|
(Source(s) of Monetary or Material Support)
|Erasmus Medical Center - Cancer Institute|
|- Brief summary||In this study we will evaluate the impact of a proton pump inhibiter induced intra gastric pH elevation on capecitabine pharmacokinetics in patients with colorectal cancer (CRC). In addition, we will study if lowering the pH by an acid beverage is able to reverse the potential PK effects of esomeprazole on capecitabine. |
|- Main changes (audit trail)|
|- RECORD||9-feb-2018 - 8-mrt-2018|