Exploratory Drug Interaction Study Between SMIs and DOACs

Maastricht University Medical Center37 enrolled

Overview

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).

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 Type

OBSERVATIONAL

Enrollment

Conditions

Solid Tumor Cancer, Lung

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (2)

Radboud UMC

Nijmegen, Gelderland, Netherlands

Maastricht UMC

Maastricht, Limburg, Netherlands

Outcomes

Primary Outcomes

DOAC trough concentration

DOAC trough concentration before and during concomitant use with an SMI

Time frame: 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

DOAC peak concentration before and during concomitant use with an SMI

Time frame: At least 7 days after start DOAC use and in combination with an SMI at steady-state (after at least 21 days)

Secondary Outcomes

Thromboembolic and bleeding events during follow-up

Time frame: within 6 months after the last blood sampling

SMI trough concentration during concomitant use with a DOAC

SMI steady-state trough concentration during concomintant use with a DOAC

Time frame: After the start of the DOAC use in combination with an SMI at steady-state (after at least 21 days)

Data from ClinicalTrials.gov

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