Clinical trial NCT05732350: Exploratory Drug Interaction Study Between SMIs and DOACs
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Solid Tumor
Cancer, Lung
Keywords: direct oral anticoagulant
targeted therapy
small molecule inhibitors
Therapeutic drug monitoring
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Radboud University Medical Center
First posted: 2023-02-17
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with cancer who will be, or are already, treated with an SMI and a DOAC simultaneously, at the MUMC+ or Radboudumc can participate in this study.

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.

Eligibility criteria: 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

Primary outcomes:
measure: DOAC trough concentration
timeFrame: At least 7 days after start DOAC use and in combination with an SMI at steady-state (after at least 21 days)
measure: DOAC peak concentration
timeFrame: At least 7 days after start DOAC use and in combination with an SMI at steady-state (after at least 21 days)
Secondary outcomes:
measure: Thromboembolic and bleeding events during follow-up
timeFrame: within 6 months after the last blood sampling
measure: SMI trough concentration during concomitant use with a DOAC
timeFrame: After the start of the DOAC use in combination with an SMI at steady-state (after at least 21 days)
Other outcomes:
measure: Thrombin generation before and during concomitant use of a DOAC and an SMI
timeFrame: At least 7 days after start DOAC use and in combination with an SMI at steady-state (after at least 21 days)
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud UMC
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastricht UMC
state: Limburg
Study officials:
affiliation: Maastricht UMC
name: Robin van Geel, PharMD, PhD
role: PRINCIPAL_INVESTIGATOR
References: