Thromboprophylaxis in good and intermediate prognosis advanced germ cell tumors (GIG-T)

The primary objective of this study is to assess the **efficacy** of thromboprophylaxis in preventing venous thromboembolic events (VTE) in patients with good and intermediate prognosis metastatic germ cell tumors (GCT) undergoing first-line cisplatin-based chemotherapy. These patients are identified as having risk factors for developing a thromboembolic event, such as elevated baseline lactate dehydrogenase (LDH), body surface area (BSA) greater than 1.9, or retroperitoneal lymph nodes (RPLN) larger than 5 cm. The clinical relevance of this objective lies in its potential to reduce the incidence of VTE, a significant complication in this patient population, thereby improving overall treatment outcomes and patient safety.

Secondary objectives include: - Assessing the safety of thromboprophylaxis and evaluating its benefit-risk ratio in this population. - Performing a cost-effectiveness analysis of thromboprophylaxis in preventing VTEs. - Prospectively confirming the prognostic value for VTEs of specific risk factors in GCT, including elevated LDH, BSA >1.9, and RPLN > 5 cm. - Assessing prospectively the prognostic value of other covariates as VTE risk factors, which include clinical covariates such as central venous catheter presence, smoking habits, physical inactivity, and body mass index (BMI), as well as laboratory covariates like platelet count, prothrombin time, partial thromboplastin time, and albumin levels.

The clinical trial focuses on **thromboprophylaxis** in patients with good and intermediate prognosis advanced germ cell tumors. The study population comprises male participants aged 18 years and older, who are in good general health and suitable for first-line cisplatin-based chemotherapy. The trial does not include female subjects or vulnerable populations. Participants were selected based on specific criteria, including a diagnosis of germ cell tumor with good or intermediate prognosis, no prior systemic cytotoxic therapy, and the ability to provide informed consent. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified. Key inclusion criteria involve patients with risk factors for venous thromboembolic events, such as elevated baseline LDH, a body surface area greater than 1.9, or retroperitoneal lymph nodes exceeding 5 cm in the long axis.

The clinical trial is designed to evaluate the efficacy of **thromboprophylaxis** in preventing venous thromboembolic events in patients with metastatic germ cell cancer undergoing first-line cisplatin-based chemotherapy. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias. The trial is expected to run from February 2023 to February 2026, with participant involvement lasting up to 13 weeks, depending on the treatment cycle and follow-up requirements.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and suitability for chemotherapy. Following randomization, participants will attend regular follow-up visits to monitor for thromboembolic events and assess safety parameters, including bleeding and adverse events. The end-of-study visit will occur approximately six weeks after the last chemotherapy cycle or residual masses surgery, whichever comes first, to evaluate the primary and secondary endpoints.

Participants are expected to remain in the study for the full duration unless specific conditions necessitate early termination. These conditions include the occurrence of a thromboembolic event, significant adverse reactions, or withdrawal of consent. The trial aims to provide comprehensive data on the proportion of patients experiencing thromboembolic events and the time to first occurrence, with all events reviewed by an independent adjudication committee. The study will also assess the cost-effectiveness of thromboprophylaxis and identify potential risk factors for thromboembolic events.

The clinical trial involves the administration of **Cisplatin**, marketed as Cisplatine Hospira 100 mg/100 ml Onco-Tain solution injectable. This medication is provided in a **solution for injection** form and is administered via **injection**. The dosage is calculated based on body surface area, with a maximum daily dose of 100 mg/m². The treatment period extends up to 13 weeks. Cisplatin is a chemical substance used as a standard-of-care therapy in this trial, particularly for patients with metastatic germ cell cancer undergoing first-line chemotherapy.

**Tinzaparin Sodium**, marketed as INNOHEP 4 500 UI anti-Xa/0.45 ml, is provided as a solution for injection in a pre-filled syringe. It is administered via **subcutaneous injection**. The maximum daily dose is 4500 anti-Xa IU, with a treatment period of up to 13 weeks. Tinzaparin Sodium is a low molecular weight heparin used as a comparator treatment in the study to assess its efficacy in thromboprophylaxis.

**Dalteparin Sodium**, marketed as Fragmin® 5000 IU, is also provided as a solution for injection. It is administered via **subcutaneous injection**. The maximum daily dose is 5000 anti-Xa IU, with a treatment period of up to 13 weeks. Dalteparin Sodium, another low molecular weight heparin, serves as a comparator treatment in the study, similar to Tinzaparin Sodium.

**Enoxaparin Sodium**, marketed as LOVENOX 4 000 UI (40 mg)/0.4 ml, is provided as a solution for injection in a pre-filled syringe. It is administered via **subcutaneous injection**. The maximum daily dose is 4000 anti-Xa IU, with a treatment period of up to 13 weeks. Enoxaparin Sodium is used as a comparator treatment in the study, contributing to the evaluation of thromboprophylaxis efficacy in the patient population.

The efficacy of thromboprophylaxis in preventing venous thromboembolic events (VTE) in patients with metastatic germ cell cancer undergoing first-line cisplatin-based chemotherapy will be assessed using both primary and secondary endpoints. The primary endpoint is the proportion of patients experiencing a thromboembolic event, which includes venous or arterial thrombosis, embolism, or unexplained death, from randomization up to 6 weeks after the first day of the last chemotherapy cycle or until residual masses surgery, whichever occurs first. These events will be reviewed by an independent clinical endpoint adjudication committee, blinded to the investigational treatment.

Secondary endpoints include the time to the first occurrence of a thromboembolic event, time to each component of the thromboembolic event composite endpoint, and safety parameters such as bleeding incidents, incidence of heparin-induced thrombocytopenia, transfusion requirements, and other adverse events graded using the NCI-CTCAE v5.0. Additional secondary endpoints involve the evaluation of comorbidity, hospitalization needs, and the number of patients needed to treat to prevent a thromboembolic event. The study will also assess the presence of central venous catheters, physical inactivity, smoking habits, germ cell histology, and baseline laboratory covariates as risk factors for thromboembolic events. The cost-effectiveness of thromboprophylaxis in high-risk patients will be evaluated, along with the proportion of patients experiencing symptomatic or asymptomatic venous thrombosis, pulmonary embolism, and unexplained death. These events will be monitored from randomization up to 6 weeks after the first day of the last chemotherapy cycle or until residual masses surgery.