Exploratory Drug Interaction Study Between SMIs and DOACs

Maastricht University Medical Centre (MUMC)

Status: Completed

Conditions: Cancer, Lung; Solid Tumor

Study type: Observational

Funder types: Other

Identifiers

NCT05732350

NL78003.068.21

Details and patient eligibility

About

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).

Full 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.

Enrollment: 37 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

37 participants in 2 patient groups

Group 1

Description:

Patients in group 1 already receive a DOAC and will start treatement with an SMI. Blood samples will be drawn before start of the SMI and during concomittant use with the SMI.

Group 2

Description:

Patients in group 2 already use a potentially relevant DOAC-SMI combination or already use an SMI and start with a DOAC. In this group, blood samples are taken after the start of concomittant use of the DOAC-SMI combination.