Exploratory Drug Interaction Study Between SMIs and DOACs

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05732350
• Other study ID #: NL78003.068.21
• Status: Completed
• Start date: November 11, 2021
• Est. completion date: February 29, 2024

Study information

• Verified date: March 2024
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: February 29, 2024
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer, Lung
• Lung Neoplasms
• Solid Tumor

Locations

Country	Name	City	State
Netherlands	Maastricht UMC	Maastricht	Limburg
Netherlands	Radboud UMC	Nijmegen	Gelderland

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Radboud University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Thrombin generation before and during concomitant use of a DOAC and an SMI	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)
Primary	DOAC trough concentration	DOAC trough concentration before and during concomitant use with an SMI	At least 7 days after start DOAC use and in combination with an SMI at steady-state (after at least 21 days)
Primary	DOAC peak concentration	DOAC peak concentration before and during concomitant use with an SMI	At least 7 days after start DOAC use and in combination with an SMI at steady-state (after at least 21 days)
Secondary	Thromboembolic and bleeding events during follow-up	Thromboembolic and bleeding events during follow-up	within 6 months after the last blood sampling
Secondary	SMI trough concentration during concomitant use with a DOAC	SMI steady-state trough concentration during concomintant use with a DOAC	After the start of the DOAC use in combination with an SMI at steady-state (after at least 21 days)