Platelet FcGammaRIIa and Risk of Venous Thromboembolism in Cancer

NCT ID: NCT05240508

Last Updated: 2023-05-17

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 600 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-01-01
• Study Completion Date: 2024-12-31

Brief Summary

Thrombosis is common and contributes significantly to morbidity and mortality in patients with cancer. At least 20% of patients with cancer develop venous thromboembolism (VTE) and another 5% will experience acute arterial thromboembolism (ATE) due to cancer and its treatment. Current guidelines recommend VTE thromboprophylaxis in high-risk outpatients. Thromboprophylaxis strategies are inadequate as 50% of high-risk patients on prophylaxis still develop a VTE, the rate of recurrent VTE is ~24% with a case fatality rate of 14.8%, and the incidence of major bleeding is ~13% with a case fatality rate of 8.9%. We and others have implicated platelets in both the pathogenesis of VTE as well as cancer growth and metastasis. To investigate a new biomarker of risk in patients with cancer, we propose a pilot study to determine whether quantification of platelet FcɣRIIa expression can discriminate risk of VTE and cancer progression. We chose platelet FcɣRIIa expression because we have found that quantifying platelet surface expression of FcγRIIa identifies patients at high and low risk of thrombotic arterial events. Thus, we hypothesize that elevated platelet expression of FcγRIIa will identify patients with cancer who are greater risk of VTE as well as cancer progression. The proposed studies leverage a clinical research program that was established in 2015 at the University of Vermont Cancer Center (Venous Thromboembolism Prevention in the Ambulatory Care Clinic [VTEPACC]) and will allow simultaneous access to research samples, thrombosis complications and cancer outcomes in order to achieve the following specific aims: 1) To determine whether platelet expression of FcγRIIa identifies cancer patients at high and low risk of VTE, and 2) To determine whether increased platelet expression of FcγRIIa is associated with a) advanced stage cancer at the time of enrollment and b) greater progression of cancer. Platelet reactivity is increased in patients with cancer and has been associated with VTE risk. Platelet expression of FcγRIIa can increase the risk of thrombosis by both increasing platelet reactivity and by promoting the procoagulant potential of platelets. In addition, platelets promote cancer by facilitating tumor vascularization, growth, and metastasis. FcγRIIa has been shown to be a key mediator of platelet secretion and cross-talk between platelets and tumor cells. Thus, we propose that increased platelet FcγRIIa expression will be linked to enhanced tumor growth and metastasis by facilitating cancer-tumor cell cross-talk and thereby the activation of platelets that leads to the release of platelet products. Identification of a biomarker capable of discriminating high and low risk of VTE will provide an important precision tool that could be combined with existing tools to guide therapy and improve outcomes. Results from aim 2 will provide key preliminary data in support of novel antiplatelet treatments to limit cancer progression.

Conditions

Venous Thromboembolism

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Active cancer diagnosis receiving cancer directed therapy
• Willing to consent to participation

Exclusion Criteria

• unwilling to provide informed consent,
• clinical or study physician declines patient enrollment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Vermont

OTHER

Sponsor Role: lead

Responsible Party

Chris Holmes

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Chris Holmes, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of Vermont

Locations

University of Vermont Medical Center

Burlington, Vermont, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Chris E Holmes, MD

Role: CONTACT

chris.holmes@med.uvm.edu

(802) 847-8400

Facility Contacts

David J Schneider, MD

Role: primary

david.schneider@uvm.edu

802-656-8955

Chris Holmes, MD, PhD

Role: backup

chris.holmes@uvm.edu

802-847-8400

Other Identifiers

1R21CA267074

Identifier Type: NIH

Identifier Source: org_study_id

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