Influence of an Acidic Beverage on the Imatinib Exposure After Major Gastrectomy

Study Overview
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Brief Summary
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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.

Official Title
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Influence of an Acidic Beverage (Coca-Cola) on the Exposure to Imatinib (GLIvec) After Major gastrecTomY in Patients With Gastrointestinal Stromal Tumors (ABILITY)

Conditions
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Gastrointestinal Stromal Tumor, Major Gastrectomy

Intervention / Treatment
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* Dietary Supplement: cola


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: water<br>imatinib intake with water | |
| Active Comparator: cola<br>imatinib intake with cola | Dietary Supplement: cola<br>* imatinib intake with coca-cola<br>* Other names: Coca-cola;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| imatinib area under the curve | imatinib exposure assessed as area under the curve | day 7; predose - 10 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of adverse events | number of adverse events will be reported and compared for both treatments | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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imatinib, gastrectomy, gastrointestinal stromal tumor, pharmacokinetics