Exploratory Drug Interaction Study Between SMIs and DOACs

Real-world Exploratory Evaluation of the Potential Drug-drug Interaction Between Anticancer Small Molecule Inhibitors and Direct Oral Anticoagulants in Patients With Solid Tumours and Exploration of the Role of Therapeutic Drug Monitoring

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT05732350

Enrollment

Registered

2023-02-17

Start date

2021-11-11

Completion date

2024-02-29

Last updated

2024-03-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cancer, Lung, Solid Tumor

Keywords

direct oral anticoagulant, targeted therapy, small molecule inhibitors, Therapeutic drug monitoring

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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

Other

Measure	Time frame	Description
Thrombin generation before and during concomitant use of a DOAC and an SMI	At least 7 days after start DOAC use and in combination with an SMI at steady-state (after at least 21 days)	Thrombin generation before and during concomitant use of a DOAC and an SMI

Countries

Netherlands

Outcome results