Journal Article

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

Ferrer-Pérez, Ana Isabel, Rojas, Mariam, Coma, Eva, de Castro, Eva Martínez, Díaz, Luis Robles, de la Camara-Gómez, Juan, Jimenez-Orozco, Encarnación, Sánchez-Cánovas, Manuel, Salgado, Mercedes, Pàmpols-Felip, Montse, Guillot-Morales, Mónica, Elías, Teresa, Carmona-Campos, Marta, Querol, Rosa, García-Ferrón, María, Álvarez-Llosa, Renata-Carola, Bouzas, Lorena París, Merino, Marta, Soria, José Manuel, Garay, David Fernández, Pelegrín-Mateo, Francisco José, Cousillas-Castiñeiras, Antia, Marrupe-González, David, Gil, Mireia, Sastre, Javier, Mompradé-Olivé, Elisabet, Muñoz, Andrés, Sánchez-Gil, Belén, García-Escobar, Ignacio, González-Villarroel, Paula, Covela-Rúa, Marta

2025

Overview

Background Colorectal 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. Aims To evaluate low molecular weight heparin (LMWH) for primary thromboprophylaxis in metastatic CRC outpatients receiving first-line systemic cancer therapy. Methods PROTINCOL (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. Discussion Risk 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 registration NCT05625932. Registered on 15 Nov 2022. Trial status The trial started recruitment on March 2023.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Adult / Aged / Anticoagulants (Medicine) / Anticoagulants - therapeutic use / Biomedical and Life Sciences / Biomedicine / Cancer Research / Care and treatment / Colorectal cancer / Colorectal Neoplasms - complications / Colorectal Neoplasms - drug therapy / Colorectal Neoplasms - pathology / Complications and side effects / Development and progression / Diagnosis / Dosage and administration / Female / Fibrinolytic Agents - administration & dosage / Fibrinolytic Agents - therapeutic use / Genetics / Health Promotion and Disease Prevention / Heparin, Low-Molecular-Weight - therapeutic use / Humans / Male / Medical care / Medicine/Public Health / Metastasis / Metastatic / Middle Aged / Multicenter Studies as Topic / Neoplasm Metastasis / Oncology / Quality management / Quality of Life / Randomized Controlled Trials as Topic / Risk factors / Study Protocol / Surgical Oncology / Thromboembolism / Thromboprophylaxis / Tinzaparin - administration & dosage / Tinzaparin - adverse effects / Tinzaparin - therapeutic use / Venous thromboembolism / Venous Thromboembolism - etiology / Venous Thromboembolism - prevention & control