Exploratory Drug Interaction Study Between SMIs and DOACs

Completed

• Conditions: Solid Tumor; Cancer, Lung

• Registration Number: NCT05732350
• Lead Sponsor: Maastricht University Medical Center

Brief Summary

The main objective of this study is to investigate the effect of small molecule inhibitors (SMIs), used in targeted therapy for tumours, on direct oral anticoagulants (DOACs).

Detailed Description

Patients who receive anticoagulant therapy in the form of a direct oral anticoagulant (DOAC) and simultaneously receive anti-cancer targeted therapy with a small molecule inhibitor (SMI), potentially have an increased risk on thromboembolic complications and bleeding events due to interfering drug-drug interactions. Some SMIs influence CYP3A4 and/or p-glycoprotein (p-gp) for which DOACs are substrates. In this study, the effect of theoretically relevant SMIs on the pharmacokinetics, efficacy and safety of DOACs in patients with solid tumours will be investigated. For this purpose, plasma concentration analyses will be performed.

Study Timeline

• Study Start: 2021-11-11
• Study First Submitted: 2023-01-27
• Study First Submitted QC: 2023-02-07
• Study First Posted: 2023-02-17
• Primary Completion: 2023-10-01
• Study Completion: 2024-02-29
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-05
• Last Update Posted: 2024-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

• Diagnosed with a solid tumour
• 18 years of age or older
• Patients receive or start treatment with an SMI-DOAC combination, that may cause a clinically significant DDI at the level of CYP3A4 and/or P-gp, based on the SmPC
• Combined use of a DOAC-SMI combination is expected to be continued at the same dose for at least three weeks
• The DOAC is used for at least seven days and the SMI has already been used for at least 21 days at time of blood collection to ensure steady-state
• Patients receive a DOAC at maintenance dose

Exclusion Criteria

• Unable to understand the information in the patient information letter
• Any concurrent medication beside the SMI and DOAC that is known to strongly inhibit or induce CYP3A4 or P-gp
• Patients who are pregnant or lactating

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
DOAC trough concentration	At least 7 days after start DOAC use and in combination with an SMI at steady-state (after at least 21 days)	DOAC trough concentration before and during concomitant use with an SMI
DOAC peak concentration	At least 7 days after start DOAC use and in combination with an SMI at steady-state (after at least 21 days)	DOAC peak concentration before and during concomitant use with an SMI

Secondary Outcome Measures

Name	Time	Method
Thromboembolic and bleeding events during follow-up	within 6 months after the last blood sampling	Thromboembolic and bleeding events during follow-up
SMI trough concentration during concomitant use with a DOAC	After the start of the DOAC use in combination with an SMI at steady-state (after at least 21 days)	SMI steady-state trough concentration during concomintant use with a DOAC

Trial Locations

Locations (2)

Radboud UMC; 🇳🇱 Nijmegen, Gelderland, Netherlands

Maastricht UMC; 🇳🇱 Maastricht, Limburg, Netherlands