Tinzaparin for the prevention of thromboembolic events in ambulatory patients with metastatic colorectal cancer receiving first line treatment: a randomised, clinical trial design

BackgroundColorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. CRC leads to increased activation of the clotting system. Since CRC patients present a higher rate of bleeding, careful evaluation of the risk/benefits of anticoagulant prophylaxis is necessary.AimsTo evaluate l...

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Authors: Salgado, M, de la Camara-Gomez, J, García-Escobar, I, Alvarez-Llosa, RC, González-Villarroel, P, Garay, DF, Pàmpols-Felip, M, Guillot-Morales, M, Pelegrín-Mateo, FJ, Jimenez-Orozco, E, Sastre, J, De Castro, EM, Coma, E, Bouzas, LP, Ferrer-Pérez, AI, Mompradé-Olivé, E, Cousillas-Castiñeiras, A, Covela-Rúa, M, Rojas, M, Querol, R, Díaz, LR, Merino, M, Gil, M, Sánchez-Cánovas, M, Elías, T, Marrupe-González, D, Sánchez-Gil, B, Carmona-Campos, M, García-Ferron, M, Soria, JM, Muñoz, A
Format: article
Status:Published version
Publication Date:2025
Country:España
Institution:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repository:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p20514
Online Access:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=20514
Access Level:Open access
Keyword:Thromboprophylaxis
Venous thromboembolism
Metastatic
Colorectal cancer
Risk factors
Genetics
Description
Summary:BackgroundColorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. CRC leads to increased activation of the clotting system. Since CRC patients present a higher rate of bleeding, careful evaluation of the risk/benefits of anticoagulant prophylaxis is necessary.AimsTo evaluate low molecular weight heparin (LMWH) for primary thromboprophylaxis in metastatic CRC outpatients receiving first-line systemic cancer therapy.MethodsPROTINCOL (NCT05625932) is a randomized, open-label (PROBE), multicenter study. Patients will receive tinzaparin (75 IU/kg) or no pharmacological prophylaxis for 4 months and will be stratified based on: BRAF/RAS mutation, primary resection tumor and antiangiogenic therapy. The study outcomes will be assessed by a blinded central independent adjudication committee.The primary efficacy endpoints will include the cumulative incidence of any venous thromboembolism (VTE) event (symptomatic or incidental) including symptomatic central venous catheter VTE. Secondary variables will be clinically relevant bleedings, health-related quality of life and the predictive value of validated risk assessment scales of VTE, including the genetic risk score (TIC-ONCO).Our hypothesis is that prophylactic LMWH will reduce the 55% relative risk to an estimated VTE incidence of 13.5%. A total of 526 patients will be required.MethodsPROTINCOL (NCT05625932) is a randomized, open-label (PROBE), multicenter study. Patients will receive tinzaparin (75 IU/kg) or no pharmacological prophylaxis for 4 months and will be stratified based on: BRAF/RAS mutation, primary resection tumor and antiangiogenic therapy. The study outcomes will be assessed by a blinded central independent adjudication committee.The primary efficacy endpoints will include the cumulative incidence of any venous thromboembolism (VTE) event (symptomatic or incidental) including symptomatic central venous catheter VTE. Secondary variables will be clinically relevant bleedings, health-related quality of life and the predictive value of validated risk assessment scales of VTE, including the genetic risk score (TIC-ONCO).Our hypothesis is that prophylactic LMWH will reduce the 55% relative risk to an estimated VTE incidence of 13.5%. A total of 526 patients will be required.MethodsPROTINCOL (NCT05625932) is a randomized, open-label (PROBE), multicenter study. Patients will receive tinzaparin (75 IU/kg) or no pharmacological prophylaxis for 4 months and will be stratified based on: BRAF/RAS mutation, primary resection tumor and antiangiogenic therapy. The study outcomes will be assessed by a blinded central independent adjudication committee.The primary efficacy endpoints will include the cumulative incidence of any venous thromboembolism (VTE) event (symptomatic or incidental) including symptomatic central venous catheter VTE. Secondary variables will be clinically relevant bleedings, health-related quality of life and the predictive value of validated risk assessment scales of VTE, including the genetic risk score (TIC-ONCO).Our hypothesis is that prophylactic LMWH will reduce the 55% relative risk to an estimated VTE incidence of 13.5%. A total of 526 patients will be required.DiscussionRisk prediction of chemotherapy-associated VTE is a compelling challenge in oncology, as VTE may result in treatment delays, impaired quality of life, and increased mortality. Patients with a single type of metastatic cancer with a high risk of VTE will be selected for study inclusion. For the first time in ambulatory prophylaxis of cancer-associated thrombosis, a precision medicine approach will be used in a clinical trial.If the individualization of antithrombotic prophylaxis can reduce the complications of outpatient cancer treatment and be cost effective, it would be of great value in the future care of patients with metastatic CRC.DiscussionRisk prediction of chemotherapy-associated VTE is a compelling challenge in oncology, as VTE may result in treatment delays, impaired quality of life, and increased mortality. Patients with a single type of metastatic cancer with a high risk of VTE will be selected for study inclusion.For the first time in ambulatory prophylaxis of cancer-associated thrombosis, a precision medicine approach will be used in a clinical trial.If the individualization of antithrombotic prophylaxis can reduce the complications of outpatient cancer treatment and be cost effective, it would be of great value in the future care of patients with metastatic CRC.DiscussionRisk prediction of chemotherapy-associated VTE is a compelling challenge in oncology, as VTE may result in treatment delays, impaired quality of life, and increased mortality. Patients with a single type of metastatic cancer with a high risk of VTE will be selected for study inclusion.For the first time in ambulatory prophylaxis of cancer-associated thrombosis, a precision medicine approach will be used in a clinical trial.If the individualization of antithrombotic prophylaxis can reduce the complications of outpatient cancer treatment and be cost effective, it would be of great value in the future care of patients with metastatic CRC.Trial registrationNCT05625932. Registered on 15 Nov 2022.Trial statusThe trial started recruitment on March 2023.

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