Platelet FcGammaRIIa and Risk of Venous Thromboembolism in Cancer

NCT05240508 | Unknown

• 1 other identifier: 1R21CA267074
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

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

Keywords

Platelet; Cancer

Outcome Measures

Primary Outcomes (2)

• venous thromboembolism occurrence

  development of VTE or PE

  18 months

• Cancer Progression

  Progression and stage of cancer

  18 months

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 a cancer diagnosis who are anticipating starting new outpatient directed chemotherapy/immunotherapy/hormonal or biologic therapy or who will be changing therapy due to disease progression or relapse.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Vermont: lead

Study Sites (1)

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma

MeSH Terms

Conditions

Venous Thromboembolism; Neoplasms

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Chris Holmes, MD PhD

  University of Vermont

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chris E Holmes, MD

CONTACT

(802) 847-8400; chris.holmes@med.uvm.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 4, 2022
• First Posted: February 15, 2022
• Study Start: January 1, 2022
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: May 17, 2023

Record last verified: 2023-05

Locations

US (1)