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

NCT ID: NCT03114618

Last Updated: 2022-04-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

416 participants

Study Classification

OBSERVATIONAL

Study Start Date

2013-03-31

Study Completion Date

2021-02-28

Brief Summary

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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

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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.

Conditions

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Cancer-associated Thrombosis Genetic Predisposition

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Servicio de Oncología Médica. HGU Gregorio Marañón. Madrid

UNKNOWN

Sponsor Role collaborator

Unitat de Genòmica de Malalties Complexes. Institut d'Investigació Sant Pau

UNKNOWN

Sponsor Role collaborator

Hospital Universitario La Paz

OTHER

Sponsor Role collaborator

Hospital Universitario Ramon y Cajal

OTHER

Sponsor Role collaborator

Hospital Clinic of Barcelona

OTHER

Sponsor Role collaborator

Hospital Universitario de Fuenlabrada

OTHER

Sponsor Role collaborator

Hospital Universitario Marqués de Valdecilla

OTHER

Sponsor Role collaborator

Complexo Hospitalario de Ourense

OTHER

Sponsor Role collaborator

Complejo Universitario Torrecárdenas, Almería

UNKNOWN

Sponsor Role collaborator

Gendiag

INDUSTRY

Sponsor Role collaborator

Ferrer inCode, S.L.

INDUSTRY

Sponsor Role collaborator

Unitat d'Hemostasia i Trombosi. Hospital de la Santa Creu i Sant Pau

UNKNOWN

Sponsor Role collaborator

LEO Pharma

INDUSTRY

Sponsor Role collaborator

Sociedad Española de Trombosis y Hemostasia (SETH)

UNKNOWN

Sponsor Role collaborator

Sociedad Española de Oncología Médica (SEOM)

UNKNOWN

Sponsor Role collaborator

University Hospital Virgen de las Nieves

OTHER

Sponsor Role collaborator

Hospital Obispo Polanco, Teruel

UNKNOWN

Sponsor Role collaborator

Complejo Hospitalario Universitario de Vigo

OTHER

Sponsor Role collaborator

Hospital General Universitario Elche

OTHER

Sponsor Role collaborator

Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz

OTHER

Sponsor Role collaborator

Hospital General de Ciudad Real

OTHER

Sponsor Role collaborator

Andres muñoz

OTHER

Sponsor Role lead

Responsible Party

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Andres muñoz

MD PhD

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Andrés J. Muñoz Martín, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital General Universitario Gregorio Marañón

Locations

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Complejo Hospitalario Torrecárdenas

Almería, Almería, Spain

Site Status

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

Site Status

Hospital Universitario de Fuenlabrada

Fuenlabrada, Madrid, Spain

Site Status

Hospital Clinic

Barcelona, , Spain

Site Status

Hospital Virgen de las Nieves

Granada, , Spain

Site Status

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status

Hospital Universitario la Paz

Madrid, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

Complejo Hospitalario de Orense

Ourense, , Spain

Site Status

Countries

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Spain

References

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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.

Reference Type RESULT
PMID: 25341889 (View on PubMed)

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.

Reference Type RESULT
PMID: 25652150 (View on PubMed)

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.

Reference Type RESULT
PMID: 29588512 (View on PubMed)

Munoz A, Ay C, Grilz E, Lopez S, Font C, Pachon V, Castellon V, Martinez-Marin V, Salgado M, Martinez E, Calzas J, Ortega L, Ruperez A, Salas E, Pabinger I, Soria JM. A Clinical-Genetic Risk Score for Predicting Cancer-Associated Venous Thromboembolism: A Development and Validation Study Involving Two Independent Prospective Cohorts. J Clin Oncol. 2023 Jun 1;41(16):2911-2925. doi: 10.1200/JCO.22.00255. Epub 2023 Feb 2.

Reference Type DERIVED
PMID: 36730884 (View on PubMed)

Other Identifiers

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ONCOTHROMB12-01

Identifier Type: -

Identifier Source: org_study_id

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