Clinical trial NCT03114618: A New Clinic-Genetic Risk Score for Predicting Venous Thromboembolic Events in Cancer Patient
Official title: Genomic Predictors Indicating the Risk of Venous Thromboembolic Disease in Cancer Patients Treated in Outpatient Clinics
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cancer-associated Thrombosis
Genetic Predisposition
Keywords: Venous thrombosis
Cancer
Risk Model Assessment
Genomic
Lead sponsor: Hospital General Universitario Gregorio Marañon
Sponsor class: OTHER
Collaborators: name: Servicio de Oncología Médica. HGU Gregorio Marañón. Madrid
name: Unitat de Genòmica de Malalties Complexes. Institut d'Investigació Sant Pau
name: Hospital Universitario La Paz
name: Hospital Universitario Ramon y Cajal
name: Hospital Clinic of Barcelona
name: Hospital Universitario de Fuenlabrada
name: Hospital Universitario Marqués de Valdecilla
name: Complexo Hospitalario de Ourense
name: Complejo Universitario Torrecárdenas, Almería
name: Gendiag
name: Ferrer inCode, S.L.
name: Unitat d'Hemostasia i Trombosi. Hospital de la Santa Creu i Sant Pau
name: LEO Pharma
name: Sociedad Española de Trombosis y Hemostasia (SETH)
name: Sociedad Española de Oncología Médica (SEOM)
name: University Hospital Virgen de las Nieves
name: Hospital Obispo Polanco, Teruel
name: Complejo Hospitalario Universitario de Vigo
name: Hospital General Universitario Elche
name: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
name: Hospital General de Ciudad Real
First posted: 2017-04-14
Enrollment: 416
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will include patients diagnosed with colorectal, esophago-gastric, biliary tract, pancreas or lung cancer who have not previously been treated with chemotherapy or chemotherapy and radiation therapy and are candidate for chemotherapy in outpatient setting

Brief summary: Venous thromboembolism (VTE) is a common disease in cancer patients and one of the major causes of cancer-associated mortality. Risk for developing VTE increases when cancer patients are receiving chemotherapy. Current risk scores for predicting cancer-associated VTE in ambulatory patients had low/moderate discrimination and clinical sensitivity. These models use clinical and biochemical parameters of the patient.

In the development of VTE genetics play a relevant role. The product Thrombo inCode (TiC) assess VTE risk prediction by using a combination of a genetic risk score (GRS) and clinical parameters from the patient. The investigators hypothesized that the GRS included in TiC combined with clinical parameter some of them associated with cancer could be better predicted by TiC than by current risk scores (Khorana score).

After publishing the primary results in 2018, we have expanded the GRS in a external validation cohort adding gliomas and biliary tract tumors. Also we have incorporated the assessment of D-dimer in order to improve the predictive capability.

Detailed description: The working hypothesis of this study establishes that the risk of cancer patients suffering a thromboembolic event is conditioned by individual genomic factors. The genes to be analyzed have clearly demonstrated their relationship with thromboembolic disease in other clinical contexts. This study is considered the initiation of a field of research in genomic risk markers indicating a risk of thrombosis in cancer patients. The ultimate goal of the study is to establish a clinic-genomic score for selecting patients with a high risk of suffering thrombotic events who can benefit from guided thromboprophylaxis. Its secondary goal is to prevent the adverse effects of ineffective therapies in other patients (low-risk patients not requiring an anti-thrombotic prophylaxis).

The aim is to demonstrate the link between the clinic-genetic profile and the risk of suffering thromboembolic events in the group of cancer patients. The working hypothesis establishes that cancer patients who develop thrombotic events will have a higher score for the thrombosis risk clinic-genetic profile than cancer patients not developing thromboembolic events. The second aim is to analyze whether the thrombosis clinic-genetic risk score improves the detection of patients at risk of suffering a thromboembolic event compared to the Khorana predictive model routinely used (Khorana score).

Current validations ongoing:

An external retrospective validation adding 250 patients more and including D-dimer and other types of high-risk neoplasm.

An external prospective validation (second ONCOTRHROMB12-01 cohort 2) adding 450 patients more and including D-dimer and other types of high-risk neoplasm.

Eligibility criteria: Inclusion Criteria:

* Patients over 18 years of age.
* Patients treated in outpatient clinics with a documented histological or cytological diagnosis for non-microcytic lung, colorectal, biliary tract cancer, pancreatic or esophago-gastric cancer at an advanced stage, locally advanced or localized not previously treated with systemic chemotherapy and/or radiation therapy who are candidate for chemotherapy in outpatient setting.
* Performance status 0-2.
* Patients signing the study informed consent form.

Exclusion Criteria:

* Life expectancy of less than 3 months.
* Patients undergoing anti-coagulant treatment before the cancer diagnosis for reasons other than a concurrent venous thromboembolic event.

Primary outcomes:
measure: Venous thromboembolism events
timeFrame: During the 18 months of follow up
Secondary outcomes:
Other outcomes:
Locations:
city: Almeria
country: Spain
facility: Complejo Hospitalario Torrecárdenas
state: Almería
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: Fuenlabrada
country: Spain
facility: Hospital Universitario de Fuenlabrada
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Granada
country: Spain
facility: Hospital Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario la Paz
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Orense
country: Spain
facility: Complejo Hospitalario de Orense
Study officials:
affiliation: Hospital General Universitario Gregorio Marañón
name: Andrés J. Muñoz Martín, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Soria JM, Morange PE, Vila J, Souto JC, Moyano M, Tregouet DA, Mateo J, Saut N, Salas E, Elosua R. Multilocus genetic risk scores for venous thromboembolism risk assessment. J Am Heart Assoc. 2014 Oct 23;3(5):e001060. doi: 10.1161/JAHA.114.001060.
citation: Rubio-Terres C, Soria JM, Morange PE, Souto JC, Suchon P, Mateo J, Saut N, Rubio-Rodriguez D, Sala J, Gracia A, Pich S, Salas E. Economic analysis of thrombo inCode, a clinical-genetic function for assessing the risk of venous thromboembolism. Appl Health Econ Health Policy. 2015 Apr;13(2):233-42. doi: 10.1007/s40258-015-0153-x.
citation: Munoz Martin AJ, Ortega I, Font C, Pachon V, Castellon V, Martinez-Marin V, Salgado M, Martinez E, Calzas J, Ruperez A, Souto JC, Martin M, Salas E, Soria JM. Multivariable clinical-genetic risk model for predicting venous thromboembolic events in patients with cancer. Br J Cancer. 2018 Apr;118(8):1056-1061. doi: 10.1038/s41416-018-0027-8. Epub 2018 Mar 28.