A New Clinic-Genetic Risk Score for Predicting Venous Thromboembolic Events in Cancer Patient

Genetic Predisposition Clinical Trial

— ONCOTHROMB  

Official title:

Genomic Predictors Indicating the Risk of Venous Thromboembolic Disease in Cancer Patients Treated in Outpatient Clinics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03114618
• Other study ID #: ONCOTHROMB12-01
• Status: Completed
• Start date: March 2013
• Est. completion date: February 2021

Study information

• Verified date: April 2022
• Source: Hospital General Universitario Gregorio Marañon
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 416
• Est. completion date: February 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cancer-associated Thrombosis
• Disease Susceptibility
• Genetic Predisposition
• Genetic Predisposition to Disease
• Thrombosis

Locations

Country	Name	City	State
Spain	Complejo Hospitalario Torrecárdenas	Almeria	Almería
Spain	Hospital Clinic	Barcelona
Spain	Hospital Universitario de Fuenlabrada	Fuenlabrada	Madrid
Spain	Hospital Virgen de las Nieves	Granada
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario la Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Complejo Hospitalario de Orense	Orense
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria

Sponsors (22)

Lead Sponsor

Collaborator

Andres muñoz

Complejo Hospitalario Universitario de Vigo, Complejo Universitario Torrecárdenas, Almería, Complexo Hospitalario de Ourense, Ferrer inCode, S.L., Gendiag, Hospital Clinic of Barcelona, Hospital General de Ciudad Real, Hospital General Universitario Elche, Hospital Obispo Polanco, Teruel, Hospital Universitario de Fuenlabrada, Hospital Universitario La Paz, Hospital Universitario Marqués de Valdecilla, Hospital Universitario Ramon y Cajal, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, LEO Pharma, Servicio de Oncología Médica. HGU Gregorio Marañón. Madrid, Sociedad Española de Oncología Médica (SEOM), Sociedad Española de Trombosis y Hemostasia (SETH), Unitat d'Hemostasia i Trombosi. Hospital de la Santa Creu i Sant Pau, Unitat de Genòmica de Malalties Complexes. Institut d'Investigació Sant Pau, University Hospital Virgen de las Nieves

Country where clinical trial is conducted

Spain, 

References & Publications (3)

Muñoz Martín AJ, Ortega I, Font C, Pachón V, Castellón V, Martínez-Marín V, Salgado M, Martínez E, Calzas J, Rupérez A, Souto JC, Martín M, Salas E, Soria JM. Multivariable clinical-genetic risk model for predicting venous thromboembolic events in patient — View Citation

Rubio-Terrés C, Soria JM, Morange PE, Souto JC, Suchon P, Mateo J, Saut N, Rubio-Rodríguez 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 — View Citation

Soria JM, Morange PE, Vila J, Souto JC, Moyano M, Trégouët 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Venous thromboembolism events	The development of venous thromboembolism will be registered	During the 18 months of follow up