NCT02800330

The Effects of the Proton Pump Inhibitor Esomeprazole on the Bioavailability of Regorafenib

The Effects of the Proton Pump Inhibitor Esomeprazole on the Bioavailability of Regorafenib in Patients With Metastatic Colorectal Cancer (mCRC) or Gastrointestinal Stromal Tumour (GIST)

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: Erasmus Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Regorafenib is a novel oral multi-kinase inhibitor which targets angiogenic, stromal and oncogenic receptor tyrosine kinases. It is currently registered for GIST and mCRC. When regorafenib is co-administered with an acid suppressive agent, the intra-gastric pH increases, and as a result the equilibrium of ionized/non-ionized regorafenib may shift to the less soluble non-ionized form which reduces regorafenib bioavailability and exposure. Since proton pump inhibitors (PPIs) are often used during regorafenib therapy, this drug-drug interaction (DDI) confronts pharmacists and oncologists with challenges in clinical practice. In this study the investigators will therefore evaluate the impact of PPI-induced intra-gastric pH elevation on regorafenib pharmacokinetics in patients with GIST and mCRC.

Detailed description

Patients will start with regorafenib in a loading phase of 21 days and will be admitted for 24 hours to the hospital for pharmacokinetic blood sampling on day 21, 49 and 77 (± 1-2 days). Patients will be randomized into 2 sequence groups (respectively sequences phase A-B-C or phase C-B-A). The patient will use regorafenib alone (phase A) or with esomeprazole for five days (phases B and C). To (completely) rule out a pH-dependent DDI between regorafenib and esomeprazole, during phase B of the study regorafenib is given concomitantly for five days, while during phase C regorafenib is given 3 hours after esomeprazole intake for five days (when the intragastric pH is maximally elevated by esomeprazole).

Conditions

• Colorectal Neoplasms
• Gastrointestinal Stromal Tumors

Interventions

Type	Name	Description
DRUG	Esomeprazole 40mg concomitantly	During phase B the patients will use esomeprazole 40mg concomitantly with regorafenib for 5 days.
DRUG	Esomeprazole 40mg before	During phase C the patients will use esomeprazole 40mg 3 hours before regorafenib for 5 days.
DRUG	Regorafenib 160mg or 120mg	Patients will use regorafenib 160mg or 120mg during all phases (A, B, C)

Timeline

• Start date: 2016-05-01
• Primary completion: 2018-02-01
• Completion: 2018-02-01
• First posted: 2016-06-15
• Last updated: 2018-08-02

Locations

1 site across 1 country: Netherlands