Tumor-educated Platelets in Venous Thromboembolism

Platelet RNA Profiling to Detect Occult Cancer in Patients With Unprovoked Venous Thromboembolism

Among patients with a first episode of unprovoked venous thromboembolism (VTE), the contemporary one-year risk of detecting occult cancer is approximately 4% to 7%. Of these cases, 30% to 60% are missed by routine limited screening for cancer. RNA profiling of platelets is a promising, highly accurate biomarker for cancer detection, but its clinical utility in patients with unprovoked VTE is unknown. The objective of the present study is to evaluate the diagnostic accuracy of platelet RNA profiling in detecting occult cancer in patients with unprovoked venous thromboembolism. Secondary objectives include evaluation of other biomarkers for cancer, prediction of bleeding, and prediction of recurrent VTE.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Venous Thromboembolism

• Study Type: Observational
• Enrollment (Actual): 476

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • KU Leuven
• Canada
  • Ottawa, Canada
    • Ottawa Hospital
• Germany
  • Dresden, Germany
    • Dresden University Clinic
• Italy
  • Bologna, Italy
    • Bologna University Hospital
  • Chieti, Italy
    • Gabriele D'Annunzio University
  • Padua, Italy
    • University of Padua
  • Varese, Italy
    • University of Insubria
• Netherlands
  • Almere, Netherlands
    • Flevoziekenhuis
  • Amsterdam, Netherlands
    • VU Medical Center
  • Amsterdam, Netherlands
    • Slotervaartziekenhuis
  • Hilversum, Netherlands
    • Tergooiziekenhuizen
  • Leiden, Netherlands
    • Leiden University Medical Center
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105AZ
      • Academic Medical Center
• Spain
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocío

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Consecutive patients of 40 years or older with a first episode of objectively confirmed, symptomatic unprovoked distal or proximal deep vein thrombosis or pulmonary embolism.

Description

Inclusion Criteria:

• First episode of objectively confirmed, symptomatic, unprovoked symptomatic pulmonary embolism and/or distal or proximal deep vein thrombosis of the leg
• Age 40 years or older
• Written informed consent

Exclusion Criteria:

• known malignant disease prior to VTE defined as a cancer diagnosis or cancer treatment within the past 5 years (of note: suspected but unconfirmed cancer at diagnosis of VTE is allowed);
• trauma or fracture of the leg, surgical procedures, general anesthesia, or immobilization greater than 3 days within previous 3 months;
• previous unprovoked venous thromboembolism;
• known hereditary or acquired thrombophilia;
• current pregnancy or puerperium (up to 3 months postpartum);
• current estrogen therapy.
• Greater than 10 days after VTE diagnosis;
• Inability for blood withdrawal at baseline;
• Inability or refusal to provide written informed consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Unprovoked VTE; Patients aged 40 years or older with a first episode of objectively confirmed, symptomatic, unprovoked deep vein thrombosis of the leg (distal or proximal) or pulmonary embolism

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any solid or hematological cancer	Adjudicated diagnosis of solid or haematological cancer which is confirmed by histology or cytology, or is unequivocally diagnosed by either imaging or tumour markers	Up to one year following venous thromboembolism

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early-stage solid cancer	Early-stage solid cancer, defined as stage I or II solid cancer according to the American Joint Commissee on Cancer criteria.	Up to one year following venous thromboembolism
Recurrent venous thromboembolism	Adjudicated recurrent VTE (see full definition in protocol)	Up to one year following venous thromboembolism
Major bleeding	Adjudicated major bleeding according to the International Society on Thrombosis and Haemostasis criteria	Up to one year following venous thromboembolism
Clinically relevant non-major bleeding	Adjudicated clinically relevant non-major bleeding according to the International Society on Thrombosis and Haemostasis criteria	Up to one year following venous thromboembolism
Composite of major bleeding and clinically relevant non-major bleeding		Up to one year following venous thromboembolism
All-cause mortality		Up to one year following venous thromboembolism
Cancer-related mortality		Up to one year following venous thromboembolism
Solid cancer		Up to one year following venous thromboembolism
Hematological cancer		Up to one year following venous thromboembolism
Composite of solid cancer and lymphoma		Up to one year following venous thromboembolism

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Study Chair: Harry Büller, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• Best MG, Sol N, Kooi I, Tannous J, Westerman BA, Rustenburg F, Schellen P, Verschueren H, Post E, Koster J, Ylstra B, Ameziane N, Dorsman J, Smit EF, Verheul HM, Noske DP, Reijneveld JC, Nilsson RJA, Tannous BA, Wesseling P, Wurdinger T. RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics. Cancer Cell. 2015 Nov 9;28(5):666-676. doi: 10.1016/j.ccell.2015.09.018. Epub 2015 Oct 29.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): October 1, 2020
• Study Completion (Actual): October 1, 2021

Study Registration Dates

• First Submitted: April 12, 2016
• First Submitted That Met QC Criteria: April 12, 2016
• First Posted (Estimate): April 15, 2016

Study Record Updates

• Last Update Posted (Actual): February 16, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: screening; venous thromboembolism; early diagnosis; occult cancer; tumor-educated platelets; platelet RNA profiling
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism
• Other Study ID Numbers: PLATO-VTE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No