Tinzaparin for the prevention of thromboembolic events in ambulatory patients with metastatic colorectal cancer receiving first line treatment: a randomised, clinical trial design
Por:
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
Publicada:
17 nov 2025
Resumen:
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.
Filiaciones:
Salgado, M:
Complexo Hosp Ourense, Med Oncol Dept, Orense, Spain
de la Camara-Gomez, J:
Complexo Hosp Univ Ourense, Med Oncol Dept, Orense, Spain
García-Escobar, I:
Hosp Gen Univ Toledo, Med Oncol Dept, Toledo, Spain
Alvarez-Llosa, RC:
Complexo Hosp Ourense, Med Oncol Dept, Orense, Spain
González-Villarroel, P:
Alvaro Cunqueiro Hosp, Vigo, Spain
Garay, DF:
Hosp Costa Sol, Marbella, Spain
Pàmpols-Felip, M:
Hosp Arnau Vilanova, Med Oncol Dept, Lleida, Spain
Guillot-Morales, M:
Hosp Univ Son Espases, Med Oncol Dept, Palma De Mallorca, Spain
Pelegrín-Mateo, FJ:
Hosp Gen Univ Dr Balmis, Hosp Gen Univ Dr, Alicante, Spain
Jimenez-Orozco, E:
Hosp Univ Jerez Frontera, Cadiz, Spain
Sastre, J:
Hosp Clin San Carlos, Madrid, Spain
De Castro, EM:
Univ Hosp Marques Valdecilla, Med Oncol Dept, IDIVAL, Santander, Spain
Coma, E:
Inst Catala Oncol LHospitalet, Barcelona, Spain
Bouzas, LP:
Ctr Oncol Galicia, La Coruna, Spain
Ferrer-Pérez, AI:
Hosp Obispo Polanco, Teruel, Spain
Mompradé-Olivé, E:
Hosp Univ Germans Trias i Pujol, Inst Catala Oncol, Badalona, Spain
Cousillas-Castiñeiras, A:
Complexo Hosp Pontevedra, Pontevedra, Spain
Covela-Rúa, M:
Hosp Univ Lucus Augusti HULA, Lugo, Spain
Rojas, M:
Hosp Clin Barcelona, Barcelona, Spain
Querol, R:
Univ Autonoma Barcelona Sabadell, Hosp Univ, Inst Invest Innovacio & Parc Tauli I3PT CERCA, Med Oncol Serv, Barcelona, Spain
Díaz, LR:
Hosp Univ 12 Octubre, Med Oncol Dept, Inst Invest I 12, Madrid, Spain
Merino, M:
LEO Pharm, Med Affairs Dept, Barcelona, Spain
Gil, M:
Gen Univ Hosp, Med Oncol Dept, Valencia, Spain
Sánchez-Cánovas, M:
Hosp Gen Univ Morales Meseguer, Murcia, Spain
Elías, T:
Hosp Univ Virgen Rocio, Inst Biomed IBIS, Seville, Spain
Marrupe-González, D:
Hosp Univ Mostoles, Madrid, Spain
Sánchez-Gil, B:
Hosp Gen La Mancha Ctr, Ciudad Real, Spain
Carmona-Campos, M:
Hosp Clin Univ Santiago CHUS, Coruna, Spain
García-Ferron, M:
Hosp Infanta Cristina Parla, Madrid, Spain
Soria, JM:
Biomed Res Inst St Pau IIB St Pau Barcelona, Genom Complex Dis Unit, Barcelona, Spain
Muñoz, A:
Hosp Univ Gregorio Maranon, Med Oncol Dept, Madrid, Spain
Univ Complutense, Madrid, Spain
Green Submitted, gold
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