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

Completed

• Conditions: Cancer-associated Thrombosis; Genetic Predisposition

• Registration Number: NCT03114618
• Lead Sponsor: Andres muñoz

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.

Study Timeline

• Study Start: 2013-03
• Study First Submitted: 2017-03-14
• Study First Submitted QC: 2017-04-10
• Study First Posted: 2017-04-14
• Primary Completion: 2020-12
• Study Completion: 2021-02
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-07
• Last Update Posted: 2022-04-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 416

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Venous thromboembolism events	During the 18 months of follow up	The development of venous thromboembolism will be registered

Trial Locations

Locations (9)

Hospital Virgen de las Nieves; 🇪🇸 Granada, Spain

Hospital Universitario Marqués de Valdecilla; 🇪🇸 Santander, Cantabria, Spain

Hospital Universitario de Fuenlabrada; 🇪🇸 Fuenlabrada, Madrid, Spain

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario la Paz; 🇪🇸 Madrid, Spain

Hospital Clinic; 🇪🇸 Barcelona, Spain

Complejo Hospitalario Torrecárdenas; 🇪🇸 Almeria, Almería, Spain

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Complejo Hospitalario de Orense; 🇪🇸 Orense, Spain