Identification of Novel Biomarkers to Aid in the Detection of Occult Cancer in Patients With Venous Thromboembolism

Venous thromboembolism is a common and serious complication in cancer, and is associated with a substantially increased morbidity and mortality. Furthermore, VTE may be the earliest sign of cancer. Recent studies, however, fail to show a clinical benefit of extended cancer screening in this patient population. Better risk prediction models are therefore warranted to identify VTE patients who would benefit from a rapid and extensive cancer screening. Inflammation and hypercoagulability are considered hallmarks of cancer, and emerging light is being shed on the potential of various markers of inflammation and coagulation in cancer diagnostics and prognostics. Among the inflammatory and thrombotic processes linked to cancer is the neutrophil release of web-like nuclear chromatin (DNA and histones), referred to as neutrophil extracellular traps (NETs). Driven by the tumor environment, NETs have recently been shown to play a central role in tumor progression, metastasis, and tumor-associated thrombosis.

The investigators hypothesize that an enhanced inflammatory state may be predictive of an underlying cancer in patients presenting with VTE. The present study is an ongoing prospective study with the primary aim to investigate the diagnostic potential of markers of inflammation, including markers of NETs, in detecting occult cancer in patients presenting with VTE. Secondary aims are to include other biomarkers of cancer, and to assess whether any or a combination of these biomarkers may be prognostic of occult cancer, recurrent thrombotic events, mortality, or cancer disease progression in VTE patients with an underlying malignancy.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Venous Thromboembolism

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Charlotte Thålin, M.D., Ph.D.; Phone Number: +46709565120; Email: charlotte.thalin@sll.se
• Study Contact Backup: Name: Håkan Wallén, M.D., Prof.; Phone Number: +46707374935; Email: hakan.wallen@ki.se

Study Locations

• Sweden
  • Stockholm, Sweden
    • Recruiting
    • Södersjukhuset
    • Principal Investigator: Charlotte Thålin, M.D., Ph.D.
    • Principal Investigator: Håkan Wallén, M.D., Prof.
    • Contact: Mårten Söderberg, M.D., Ph.D.; Phone Number: +4686160000; Email: marten.soderberg@sll.se
  • Stockholm, Sweden, 18350
    • Recruiting
    • Danderyd Hospital
    • Contact: Charlotte Thålin, M.D., Ph.D.; Phone Number: +46709565120; Email: charlotte.thalin@sll.se
    • Contact: Lena Gabrielsson; Phone Number: +46737121286; Email: lena.gabrielsson@sll.se
    • Principal Investigator: Charlotte Thålin, M.D., Ph.D.
    • Principal Investigator: Håkan Wallén, M.D., Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Consecutive patients age >18 years with objectively confirmed venous thromboembolism (thrombosis in the deep venous system of upper or lower extremities or iliac veins and/or pulmonary embolism) diagnosed < 2 days.

Description

Inclusion Criteria:

• Venous thromboembolism (thrombosis in the deep venous system of upper or lower extremities or iliac veins and/or pulmonary embolism) as detected by ultrasonography, phlebography, computer tomography, or angiography;
• > 18 years or older;
• Written informed consent

Exclusion Criteria:

• > 2 days after VTE diagnosis;
• No blood withdrawal at baseline

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Venous thromboembolism; Patients presenting with venous thromboembolism (thrombosis in the deep venous system of upper or lower extremities or iliac veins and/or pulmonary embolism) as detected by ultrasonography, phlebography, computer tomography, or angiography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer	Patients diagnosed with VTE will be referred for a limited cancer screening according to current guidelines. Cancer diagnosis - if not present at inclusion - will be obtained during a two-year follow-up from hospital records and/or the Swedish cancer registry	Within 2 years from study inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent thrombotic event	Recurrent thrombotic event (arterial or venous thrombosis) will be obtained during a two-year follow-up from hospital records and/or the Swedish national patient registry	Within 2 years from study inclusion
All-cause mortality	All-cause mortality will be obtained during a two-year follow-up from hospital records and/or the Swedish death registry	Within 2 years from study inclusion
Cancer progression among enrolled patients with a cancer diagnosis at study inclusion	Patients with cancer progression will be identified during a two-year follow-up from hospital records and/or the Swedish cancer registry	Within 2 years from study inclusion

Collaborators and Investigators

• Sponsor: Danderyd Hospital
• Collaborators: Karolinska Institutet
• Investigators: Principal Investigator: Charlotte Thålin, M.D., Ph.D., Karolinska Institutet; Principal Investigator: Håkan Wallén, M.D., Prof., Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2028

Study Registration Dates

• First Submitted: December 17, 2018
• First Submitted That Met QC Criteria: December 18, 2018
• First Posted (Actual): December 20, 2018

Study Record Updates

• Last Update Posted (Actual): December 20, 2018
• Last Update Submitted That Met QC Criteria: December 18, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Biomarkers; Venous thromboembolism; Early diagnosis; Occult cancer; Neutrophil extracellular traps
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism
• Other Study ID Numbers: dnr2017/260-31/4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No