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

Phase 1

Terminated

• Conditions: Gastrointestinal Stromal Tumor; Major Gastrectomy
• Interventions: Dietary Supplement: cola

• Registration Number: NCT02185937
• Lead Sponsor: Radboud University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-07-07
• Study First Submitted QC: 2014-07-09
• Study First Posted: 2014-07-10
• Study Start: 2014-08
• Primary Completion: 2016-11
• Study Completion: 2016-11
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-04
• Last Update Posted: 2020-12-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
cola	cola	imatinib intake with cola

Primary Outcome Measures

Name	Time	Method
imatinib area under the curve	day 7; predose - 10 hours after dosing	imatinib exposure assessed as area under the curve

Secondary Outcome Measures

Name	Time	Method
number of adverse events	2 weeks	number of adverse events will be reported and compared for both treatments

Trial Locations

Locations (1)

Radboudumc; 🇳🇱 Nijmegen, Netherlands