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

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

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.

Study Overview

• Status: Terminated
• Conditions: Gastrointestinal Stromal Tumor; Major Gastrectomy
• Intervention / Treatment: Dietary supplement: cola

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: water; imatinib intake with water
Active Comparator: cola; imatinib intake with cola	Dietary supplement: cola; imatinib intake with coca-cola; Other Names: Coca-cola

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Nielka van Erp, Radboud university medical center

Publications and helpful links

General Publications

• Lubberman FJE, Gelderblom H, Wilmer CM, Kweekel DM, Desar IME, Colbers A, Burger D, van der Graaf WTA, van Erp N. Does a glass of Coke boost the exposure to imatinib in gastrointestinal stromal tumour patients after gastrectomy? Br J Clin Pharmacol. 2017 Oct;83(10):2312-2314. doi: 10.1111/bcp.13333. Epub 2017 Jul 4. No abstract available.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: July 7, 2014
• First Submitted That Met QC Criteria: July 9, 2014
• First Posted (Estimate): July 10, 2014

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 4, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; gastrectomy; gastrointestinal stromal tumor; imatinib
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: ABILITY