Exploratory Drug Interaction Study Between SMIs and DOACs

Sponsor

Maastricht University Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05732350

Collaborator

Radboud University Medical Center (Other)

Enrollment

Locations

25.6

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Cancer, Lung

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

50 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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

Actual Study Start Date :

Nov 11, 2021

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Group 1 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 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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Radboud UMC	Nijmegen	Gelderland	Netherlands	6500HB
2	Maastricht UMC	Maastricht	Limburg	Netherlands	6202AZ

Sponsors and Collaborators

Maastricht University Medical Center
Radboud University Medical Center

Investigators

Principal Investigator: Robin van Geel, PharMD, PhD, Maastricht UMC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Maastricht University Medical Center

ClinicalTrials.gov Identifier:

NCT05732350

Other Study ID Numbers:

NL78003.068.21

First Posted:

Feb 17, 2023

Last Update Posted:

Feb 17, 2023

Last Verified:

Feb 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Maastricht University Medical Center

direct oral anticoagulant

targeted therapy

small molecule inhibitors

Therapeutic drug monitoring

Additional relevant MeSH terms:

Lung Neoplasms

Study Results

No Results Posted as of Feb 17, 2023