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

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

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.

Study Overview

• Status: Completed
• Conditions: Genetic Predisposition; Cancer-associated Thrombosis

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.

• Study Type: Observational
• Enrollment (Actual): 416

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Hospital Clinic
  • Granada, Spain
    • Hospital Virgen de las Nieves
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Hospital Universitario Ramon y Cajal
  • Orense, Spain
    • Complejo Hospitalario de Orense
  • Almería
    • Almeria, Almería, Spain
      • Complejo Hospitalario Torrecárdenas
  • Cantabria
    • Santander, Cantabria, Spain
      • Hospital Universitario Marques de Valdecilla
  • Madrid
    • Fuenlabrada, Madrid, Spain
      • Hospital Universitario de Fuenlabrada

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Venous thromboembolism events	The development of venous thromboembolism will be registered	During the 18 months of follow up

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (ACTUAL): December 1, 2020
• Study Completion (ACTUAL): February 1, 2021

Study Registration Dates

• First Submitted: March 14, 2017
• First Submitted That Met QC Criteria: April 10, 2017
• First Posted (ACTUAL): April 14, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 14, 2022
• Last Update Submitted That Met QC Criteria: April 7, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Cancer; Venous thrombosis; Genomic; Risk Model Assessment
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Disease Attributes; Embolism and Thrombosis; Disease Susceptibility; Thrombosis; Genetic Predisposition to Disease
• Other Study ID Numbers: ONCOTHROMB12-01

Plan for Individual participant data (IPD)

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