Phase III Randomized Trial on Biomarker Staging Versus Conventional Staging in Early-Stage Endometrial Cancer with Paclitaxel and Carboplatin

The primary objective of the BIOMEC trial is to investigate the **non-inferiority** of biomarker staging compared to conventional staging in selecting women with presumed early-stage **endometrial cancer** for adjuvant treatment. This is clinically relevant as it may offer a more precise and potentially less invasive method for determining appropriate treatment pathways, potentially improving patient outcomes and resource allocation.

Secondary objectives include:

• To assess **recurrence-free survival**.
• To evaluate **Health Related Quality of Life**.
• To assess **Lymphedema** following sentinel lymph node biopsy.
• To evaluate **Frailty**.
• To assess **Sarcopenia**.
• To evaluate **Health Economics**.
• To assess **adverse events** and postoperative complications.

The clinical trial focuses on women diagnosed with **endometrial cancer**, specifically those with presumed early-stage disease. The study population comprises adult females aged 18 years and older, with no male participants included. Participants are required to have a histologically confirmed primary carcinoma in the endometrium and must be suitable candidates for both surgery and adjuvant treatment. The trial excludes vulnerable populations and requires participants to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, indicating they are in relatively good health. Additionally, participants must have adequate organ function, as defined by specific laboratory criteria. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the **efficacy** of biomarker staging compared to conventional staging in women with presumed early-stage **endometrial cancer**. This is a phase III, open-label, randomized trial. The study will involve the administration of **paclitaxel** and **carboplatin**, both delivered as a concentrate for solution for infusion via the intravenous route. The trial is expected to run until September 28, 2029, with recruitment starting on September 1, 2023. Participants will be involved in the study for a maximum treatment period of 18 months.

The trial will include several key visits: an initial screening visit, regular follow-up visits, and an end-of-study visit. During the screening visit, eligibility will be confirmed based on criteria such as histologically confirmed primary carcinoma in the endometrium, presumed FIGO stage I-II, and adequate organ function. Follow-up visits will monitor the participants' response to treatment and any adverse events. The end-of-study visit will assess the primary endpoint of overall survival and secondary endpoints, including recurrence-free survival and quality of life measures.

Participants are expected to comply with the study procedures and maintain an ECOG performance status of 0-2. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or any adverse events that compromise the safety of the participant. The trial aims to provide valuable insights into the non-inferiority of biomarker staging in selecting appropriate adjuvant treatment for women with early-stage endometrial cancer.

The clinical trial involves the administration of **Paclitaxel**, a cytostatic agent, as part of the experimental treatment regimen. Paclitaxel is provided in the form of a concentrate for solution for infusion. The active substance, paclitaxel, is of chemical origin. The medication is administered intravenously, with a maximum daily dose of 175 mg/m². The treatment period for paclitaxel is set at a maximum of 18 weeks. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

In addition to paclitaxel, the trial also includes the administration of **Carboplatin**, another cytostatic agent. Carboplatin is similarly provided as a concentrate for solution for infusion, with the active substance being chemically derived. The administration route is intravenous, with a maximum daily dose of 5 units, as specified in the trial protocol. The treatment period for carboplatin is also set at a maximum of 18 weeks. Monitoring of participant compliance with the dosing schedule will be conducted to maintain protocol adherence.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial documentation. The focus of the trial is to evaluate the efficacy of the experimental medications, paclitaxel and carboplatin, in the context of biomarker staging for women with presumed early-stage endometrial cancer. The trial aims to investigate the non-inferiority of biomarker staging compared to conventional staging methods.

The efficacy of the clinical trial titled "BIOMarkers in Endometrial Cancer" will be assessed using a combination of primary and secondary endpoints. The primary endpoint for evaluating efficacy is **overall survival**. Secondary endpoints include recurrence-free survival, quality of life scores measured by EORTC QLQ-C30, QLQ-EN24, and EQ5D-5L, as well as LYMQOL and volume measurement, lymphosintigraphy results, and the Clinical Frailty Scale-9 score. Additional assessments will involve imaging techniques such as CT scans analyzed with applicable software, and economic evaluations including QALY and cost per patient. The trial will also monitor 30-day post-operative complications and adverse events.