Platelet FcGammaRIIa and Risk of Venous Thromboembolism in Cancer

• ClinicalTrials.gov Identifier: NCT05240508
• Recruitment Status: Recruiting
• First Posted: February 15, 2022
• Last Update Posted: April 12, 2022
• Sponsor: University of Vermont
• Information provided by (Responsible Party): Chris Holmes, University of Vermont

Tracking Information

• First Submitted Date: February 4, 2022
• First Posted Date: February 15, 2022
• Last Update Posted Date: April 12, 2022
• Actual Study Start Date: January 1, 2022
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 4, 2022)

• venous thromboembolism occurrence [ Time Frame: 18 months ]
  development of VTE or PE
• Cancer Progression [ Time Frame: 18 months ]
  Progression and stage of cancer

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Platelet FcGammaRIIa and Risk of Venous Thromboembolism in Cancer
• Official Title: Platelet FcGammaRIIa and Risk of Venous Thromboembolism in Cancer
• 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.
• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

plasma

• 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.
• Condition: Venous Thromboembolism
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 4, 2022): 600
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2024
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Chris E Holmes, MD; (802) 847-8400; chris.holmes@med.uvm.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05240508
• Other Study ID Numbers: 1R21CA267074( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Chris Holmes, University of Vermont
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Vermont
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Chris Holmes, MD PhD; University of Vermont

• PRS Account: University of Vermont
• Verification Date: April 2022