Exploratory Drug Interaction Study Between SMIs and DOACs

NCT05732350 | Completed DMC

• 1 other identifier: NL78003.068.21
• Study Type: observational
• Target: 37
• Locations: 1 country
• Sites: 2

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).

Conditions

Solid Tumor; Cancer, Lung

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (2)

• Thromboembolic and bleeding events during follow-up

  within 6 months after the last blood sampling

• 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)

Other Outcomes (1)

• 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)

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Diagnosed with a solid tumour
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Radboud University Medical Center: collaborator

Study Sites (2)

Radboud UMC

Nijmegen, Gelderland, 6500HB, Netherlands

Location

Maastricht UMC

Maastricht, Limburg, 6202AZ, Netherlands

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Citrate whole blood samples, EDTA whole blood samples

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Robin van Geel, PharMD, PhD

  Maastricht UMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2023
• First Posted: February 17, 2023
• Study Start: November 11, 2021
• Primary Completion: October 1, 2023
• Study Completion: February 29, 2024
• Last Updated: March 6, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)