Evaluation of Tinzaparin Sodium on Biomarker Modulation in FIGO Stage III-IV Epithelial Ovarian Cancer Patients Undergoing Neoadjuvant Chemotherapy

The primary objective of this study is to evaluate the effects of **tinzaparin** on changes in levels of CA-125 in patients with epithelial ovarian cancer (EOC) undergoing neoadjuvant chemotherapy (NACT). CA-125 is a tumor marker used in the management of ovarian cancer, and its levels can provide insights into the disease's progression and response to treatment. Understanding the impact of tinzaparin on CA-125 levels is clinically relevant as it may offer a potential therapeutic strategy to improve patient outcomes.

The secondary objectives include exploring the impact of tinzaparin on the dynamics of a spectrum of immunological and coagulation factors in EOC patients receiving NACT. Additionally, the study will describe the compliance with tinzaparin injections and document any adverse events associated with its use. Thromboembolic events will also be registered, providing a comprehensive assessment of the safety and efficacy of tinzaparin in this patient population.

The clinical trial involves participants diagnosed with **epithelial ovarian cancer**, specifically targeting adult females aged 18 and above. The study population is exclusively female, with no male participants included, and does not involve any vulnerable populations. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants are selected based on specific criteria, including a histological diagnosis of high-grade serous carcinoma, endometrioid carcinoma, or clear cell carcinoma, and must have a FIGO stage III-IV disease. They are required to have a WHO Performance Status of 0-1 and a CA-125 level of at least 250 kIE/L at diagnosis. The weight range for participants is between 50-150 kg. Lifestyle factors such as diet and physical activity are not specified in the trial data. The selection process ensures that participants are planned for a platinum doublet regimen, aligning with the study's primary objective to evaluate the effects of tinzaparin on changes in CA-125 levels in patients receiving neoadjuvant chemotherapy (NACT).

The clinical trial is designed to evaluate the effects of **tinzaparin sodium** on biomarkers in patients with FIGO Stage III-IV epithelial ovarian cancer undergoing neoadjuvant chemotherapy. This study is a randomized, controlled, double-blind pilot trial, conducted over an estimated duration from July 2022 to December 2026. The primary objective is to assess changes in CA-125 levels, with secondary endpoints including the evaluation of hemoglobin, platelets, leucocytes, CRP, albumin, IL-6, and VEGF levels, as well as compliance to tinzaparin injections and the occurrence of adverse events.

Participants will be involved in the study for a maximum treatment period of 28 days, with the possibility of early termination if adverse events occur or if the participant withdraws consent. The trial includes a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as a histological diagnosis of high-grade serous carcinoma, endometrioid carcinoma, or clear cell carcinoma, and a CA-125 level of ≥250 kIE/L at diagnosis. Follow-up visits will occur before each chemotherapy cycle and preoperatively before debulking surgery, with additional assessments three weeks post-chemotherapy.

The trial will utilize subcutaneous injections of tinzaparin sodium, with a maximum daily dose of 8000 IU and a total dose not exceeding 1568000 IU. Participants will be monitored for compliance and any adverse events related to the treatment. The study aims to provide insights into the potential benefits of tinzaparin sodium in managing biomarkers associated with epithelial ovarian cancer, contributing to the understanding of its role in neoadjuvant chemotherapy regimens.

The clinical trial involves the administration of **tinzaparin sodium**, an antithrombotic agent, as the experimental medication. Tinzaparin sodium is provided in a pharmaceutical form designated as PHF00231MIG. The medication is administered via **subcutaneous injection**. The dosing regimen allows for a maximum daily dose of 8000 IU (international units) and a cumulative maximum dose of 1568000 IU over a treatment period of up to 28 days. The active substance, tinzaparin sodium, is derived from a polymer origin and is classified under the ATC code B01AB10. The trial aims to assess the effects of tinzaparin on biomarkers in patients with FIGO Stage III-IV ovarian cancer undergoing neoadjuvant chemotherapy.

In addition to the experimental treatment, participants may receive standard-of-care therapy as part of their treatment regimen. The study does not utilize a placebo or comparator treatment. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial's primary objective is to evaluate the impact of tinzaparin on changes in levels of CA-125, a biomarker in epithelial ovarian cancer (EOC) patients receiving neoadjuvant chemotherapy (NACT).

Efficacy in this clinical trial will be assessed by evaluating the effects of **tinzaparin sodium** on specific biomarkers in patients with FIGO Stage III-IV ovarian cancer undergoing neoadjuvant chemotherapy. The primary endpoint for efficacy evaluation is the change in levels of CA-125, a tumor marker, measured before cycles one to four of chemotherapy and preoperatively before debulking surgery (DPDS). Secondary endpoints include the measurement of CA-125 levels before cycles five to seven of chemotherapy and three weeks after the last cycle. Additionally, levels of hemoglobin, platelets, leucocytes, C-reactive protein (CRP), albumin, interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) will be assessed before each chemotherapy cycle, preoperatively before DPDS, and three weeks post-chemotherapy.

The compliance to tinzaparin injections and the occurrence of adverse events related to tinzaparin will also be evaluated as part of the secondary endpoints. Furthermore, the trial will monitor for objectively confirmed venous thromboembolism (VTE), including pulmonary embolism, lower-limb deep vein thrombosis, or upper extremity deep vein thrombosis, as well as death due to VTE. These efficacy parameters will be collected and analyzed at specified timepoints throughout the trial to determine the impact of tinzaparin on the targeted biomarkers and clinical outcomes in the study population.