Phase II Study on the Efficacy of Chemoradiation with Cisplatin and Carboplatin in Early-Stage Vulvar Cancer with Sentinel Lymph Node Macrometastasis

The primary objective of the study is to investigate the safety of replacing **inguinofemoral lymphadenectomy** (with or without adjuvant (chemo)radiation) by chemoradiation alone in patients with early-stage **vulvar cancer** who have a macrometastasis (> 2mm) in the sentinel lymph node. This is clinically relevant as it aims to reduce the morbidity associated with surgical interventions while maintaining effective cancer control.

Secondary objectives include evaluating the short- and long-term morbidity associated with this treatment approach. This assessment is crucial for understanding the broader impact of the treatment on patient health and quality of life over time.

The clinical trial involves a total of **40 participants** diagnosed with **vulvar cancer**. The study population is exclusively female, with an age range of 18 years and older. Participants were selected based on specific criteria, including a histologically confirmed primary squamous cell carcinoma of the vulva, a performance status of 0, 1, or 2 on the ECOG Scale, and a life expectancy of more than 12 weeks. The trial excludes individuals with enlarged or suspicious inguinofemoral lymph nodes at imaging. Participants are required to have adequate bone marrow, renal, and liver function. The study does not include a vulnerable population, and all participants must be able to understand the study requirements and comply with follow-up procedures. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is designed to evaluate the safety of replacing inguinofemoral lymphadenectomy with chemoradiation alone in patients with early-stage **vulvar cancer** who have a macrometastasis in the sentinel lymph node. This is a prospective phase 2 treatment trial, employing a randomized, double-blind, controlled methodology to ensure the reliability and validity of the results. The trial is expected to run from November 19, 2020, to March 1, 2029, with recruitment having commenced on January 29, 2021.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically confirmed primary squamous cell carcinoma of the vulva, a performance status of 0, 1, or 2 on the ECOG Scale, and adequate bone marrow, renal, and liver function. Follow-up visits will be scheduled to monitor treatment effects and collect data on primary and secondary endpoints, including groin recurrences, treatment-related morbidity, disease-specific survival, and patient-reported quality of life. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any remaining health concerns are addressed.

The expected length of participant involvement is contingent upon the treatment period, which is capped at five weeks, with a maximum total dose of 200 mg/m² for **cisplatin** and 2000 mg/m² for **carboplatin** administered via IV infusion. Conditions that may lead to early termination from the study include adverse reactions to the treatment, withdrawal of consent, or any significant protocol deviations. The trial aims to provide valuable insights into the potential benefits and risks of chemoradiation as a treatment modality for vulvar cancer, contributing to the optimization of therapeutic strategies for this condition.

The clinical trial involves the administration of **Cisplatin Accord Healthcare 1 mg/ml**, a **solution for infusion**. This experimental medication contains the active substance **cisplatin**, a chemical compound classified under the ATC code L01XA01. The pharmaceutical form is a concentrate for solution for infusion, intended for intravenous (IV) administration. The dosing regimen specifies a maximum daily dose of 40 mg/m², with a total maximum dose of 200 mg/m² over a treatment period of up to 5 days. The administration of cisplatin is monitored to ensure participant compliance and safety throughout the trial.

Additionally, the trial includes the use of **Carboplatin Accord Healthcare 10 mg/ml**, also a **solution for infusion**. The active substance in this medication is **carboplatin**, another chemical compound, categorized under the ATC code L01XA02. Similar to cisplatin, carboplatin is provided as a concentrate for solution for infusion and is administered intravenously. The dosing schedule allows for a maximum daily dose of 400 mg/m², with a total maximum dose of 2000 mg/m² over a 5-day treatment period. Compliance with the dosing schedule is closely monitored to ensure the integrity of the trial data and participant safety.

Both medications are provided by Accord Healthcare B.V. and are not formulated for pediatric use. The trial does not involve any orphan drug designations. The study aims to evaluate the safety and efficacy of these chemotherapeutic agents in the context of the trial's objectives, with careful monitoring of dosing schedules and participant adherence to the treatment protocol.

Efficacy in the clinical trial titled "GROINSS-V III; Groningen International Study on Sentinel node in Vulvar cancer III" will be assessed using specific primary and secondary endpoints. The primary endpoint for evaluating efficacy is the rate of **groin recurrences** in patients. Secondary endpoints include treatment-related morbidity, disease-specific survival, and patient-reported quality of life. These endpoints will provide a comprehensive assessment of the treatment's impact on patients with early-stage vulvar cancer who have a macrometastasis in the sentinel lymph node.

The trial aims to investigate the safety of replacing inguinofemoral lymphadenectomy with chemoradiation alone. The efficacy parameters will be collected and analyzed at various timepoints throughout the study, although specific timepoints are not detailed in the provided data. The trial is designed to ensure that the collected data accurately reflects the treatment's efficacy in achieving the desired clinical outcomes. The study will utilize validated scales and patient-reported outcomes to measure the secondary endpoints, ensuring a robust evaluation of the treatment's impact on quality of life and disease progression.