Gastrointestinal Stromal Tumor, Major Gastrectomy
Conditions
Keywords
imatinib, gastrectomy, gastrointestinal stromal tumor, pharmacokinetics
Brief summary
The most common sites for GIST to occur are the stomach (60-70%) and proximal small intestines (20-25%). Therefore patients with GIST often have altered GI-tract due to tumor resection or palliative surgery which might affect imatinib exposure. Indeed, Yoo et al. showed that steady state imatinib trough levels in patients with advanced GISTs after major gastrectomy are lower compared to patients with a previous wedge resection or without gastric surgery. Patients that underwent major gastrectomy had an average imatinib plasma trough levels below 1000 µg/L. This while imatinib trough levels above 1000 µg/L are correlated to more beneficial treatment out-comes (longer Progression Free Survival). Since imatinib easily and rapidly dissolves at pH 5.5 or less, a lack of gastric acid secretion might be causing the decreased exposure in the patients that underwent major gastrectomy. Therefore the investigators would like to study if the exposure to imatinib in patients after major gastrectomy can be improved by creating a more acidic environment for absorption through combining imatinib intake with Coca-Cola.
Interventions
DIETARY_SUPPLEMENTcola
imatinib intake with coca-cola
Sponsors
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients ≥ 18 years of age * Patients with GIST, who previously underwent major gastrectomy * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 * Already selected to receive imatinib therapy in a dose of 400-800mg imatinib daily, as judged by the treating physician and with respect for and in agreement with the registration guidelines * Subject is able and willing to sign the Informed Consent Form prior to screening
Exclusion criteria
* Concomitant administration of any anti-cancer therapies (e.g. chemo-therapy, other targeted therapy, experimental drug, etc) other than imatinib * Concomitant use of medication which strongly inhibits or induces CYP3A4 * Refractory nausea and vomiting, malabsorption with other causes than gastrectomy or external biliary shunt that would preclude adequate absorption. * Unwillingness to use Coca-Cola * Unwillingness or inability to swallow whole tablets * Inability to comply with the requirements of the protocol * Inability to understand the nature and extent of the study and the procedures required * Participation in a drug study within 60 days prior to the first day of this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| imatinib area under the curve | day 7; predose - 10 hours after dosing | imatinib exposure assessed as area under the curve |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| number of adverse events | 2 weeks | number of adverse events will be reported and compared for both treatments |
Countries
Netherlands
Outcome results
None listed