Clinical trial NCT04301362: Biomarkers of Thrombosis as Predictors of Venous Thromboembolism Risk in Cancer Patients
Official title: FIIT Project - Biomarkers of Thrombosis as Predictors of Venous Thromboembolism Risk in Cancer Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cancer
Thromboembolism
Thrombosis
Biomarkers
Keywords: Khorana
Thrombin generation
Venous thromboembolism
Lead sponsor: Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.
Sponsor class: OTHER_GOV
Collaborators: name: LEO Pharma
name: Diagnostica Stago
First posted: 2020-03-10
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cancer patients admitted to Medical Oncology, Clinical Hematology, and Pulmonology consultations at Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal.

Brief summary: The main venous thromboembolism (VTE) risk prediction model for ambulatory cancer patients is Khorana. Cancer thrombosis is associated with elevated thrombin generation. Its quantification is a promising method for evaluating patient's thrombotic profile.

This study aims to develop a predictive model of VTE risk in ambulatory cancer patients, combining thrombosis biomarkers (D-dimers and thrombin generation potential) with the Khorana score.

This is a prospective observational study that includes newly diagnosed cancer patients proposed for anti-tumor treatment (chemotherapy, immunotherapy or targeted therapies). Patients with disease progression are allowed if chemotherapy-free for 3 months. A 6-month mean incidence of VTE 6-10% is expected, requiring a sample size of 600 patients. Blood sample is collected at inclusion to analyze thrombosis biomarkers and blood count. The primary endpoint is the occurrence of symptomatic or incidental VTE within 6 months of inclusion. Models will follow a logistic approach with K-fold cross-validation (k=10). Model quality will be assessed with Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC). Decision for entering predictors in multivariate models will be based on p \<.10 in the univariate analysis.

Detailed description: The main aims will be the following:

* Evaluate the utility of the combination of thrombosis biomarkers (D-dimers and thrombin generation potential) with the Khorana score in order to stratify VTE risk in ambulatory cancer patients;
* Determine the potential of this new score in the stratification of cancer patients into high- and low-risk VTE groups, in order to identify patients who would benefit from primary thromboprophylaxis;
* Determine the applicability of the thrombin generation test as an independent factor in the stratification of VTE risk in the cancer population under study;
* Determine the predictive value of D-dimers in the cancer population under study (high versus low risk discrimination).

Eligibility criteria: Inclusion Criteria:

* Patients older than 18 years.
* Newly diagnosed cancer patients, proposed for anti-tumor medical treatment (chemotherapy, immunotherapy and targeted therapies).
* Patients with a cancer diagnosis, previously under medical anti-tumor treatments, with disease progression proposed for a new line of anti-tumor treatment, who have not recently received chemotherapy (within the last three months).
* Follow-up in Medical Oncology, Clinical Hematology, and Pulmonology consultations at Centro Hospitalar Vila Nova de Gaia/Espinho.

Exclusion Criteria:

* Major bleeding in the last 3 months.
* Major surgery in the last 28 days.
* Patients on anticoagulation/antithrombotic therapy
* Pregnant or breastfeeding women.
* Patients previously submitted to bone marrow transplantation.
* Inaccessibility to the results of the biomarkers or other elements provided for in the Khorana score.

Primary outcomes:
measure: Occurrence of symptomatic or incidental VTE
timeFrame: 6 months
Secondary outcomes:
measure: Mortality
timeFrame: 6 months
measure: Risk factors for the development of VTE
timeFrame: 6 months
measure: Major Bleeding
timeFrame: 6 months
Other outcomes:
Locations:
city: Vila Nova De Gaia
country: Portugal
facility: Centro Hospitalar Vila Nova de Gaia/Espinho
Study officials:
affiliation: Centro Hospitalar Vila Nova de Gaia/Espinho
name: David Ferreira, MD
role: PRINCIPAL_INVESTIGATOR
References: