Evaluation of Adjuvant Therapy with Carboplatin and Cisplatin in Early-Stage, Intermediate-Risk Cervical Cancer Post-Radical Surgery

The primary objective of this international randomized trial, titled CERVANTES, is to evaluate whether **adjuvant therapy** provides a disease-free survival benefit following radical surgery in patients with early-stage, intermediate-risk **cervical cancer**. The study aims to determine the disease-free survival from the day of randomization, with a total of 514 patients required to achieve 80% power at a 5% significance level. The trial will test the difference between the treatment arms using the Cox proportional hazards model, with a non-inferiority margin of 5% for 2-year disease-free survival, accounting for an expected drop-out rate of 10%. The clinical relevance of this study lies in its potential to inform treatment decisions and improve outcomes for patients with this specific cancer profile.

The clinical trial involves a total of **50 participants** diagnosed with **early-stage, intermediate-risk cervical cancer**. The study population is exclusively female, with an age range of 18 to 85 years. Participants were selected based on specific criteria, including having recently undergone radical hysterectomy and lymph node staging, and having pathologically confirmed invasive cervical cancer. The trial excludes male subjects and does not involve a vulnerable population. Participants are required to have a good general health status, as indicated by an ECOG performance status of 0 to 1, and must be deemed suitable for adjuvant external beam radiotherapy following surgery. Lifestyle considerations such as diet and physical activity are not specified in the trial data. The selection criteria ensure that participants have no evidence of distant metastases and negative pelvic lymph nodes, with a negative HIV test required for those from high-risk countries. The trial aims to evaluate the association of adjuvant therapy with disease-free survival benefit post-surgery.

The clinical trial is designed to evaluate the efficacy of **adjuvant therapy** in patients with early-stage, intermediate-risk cervical cancer following radical surgery. This is a randomized, controlled, double-blind trial with a primary endpoint of disease-free survival, analyzed three years after the randomization of the last patient. The trial aims to recruit 514 participants to achieve 80% power at a 5% significance level, with a non-inferiority margin of 5%. The trial is expected to conclude by December 31, 2032, with recruitment starting on May 20, 2023.

Participants will undergo a series of study visits, beginning with an inclusion visit to confirm eligibility based on criteria such as recent radical hysterectomy, pathologically confirmed invasive cervical cancer, and specific tumor-related risk factors. Follow-up visits will be scheduled to monitor the participants' health status, adherence to the treatment protocol, and any adverse events. The end-of-study visit will assess the primary and secondary endpoints, including overall survival, pelvic disease-free survival, health-related quality of life, and treatment-related adverse events.

The expected duration of participant involvement is up to eight weeks, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include the development of distant metastases, significant adverse events, or withdrawal of consent. The trial will utilize **carboplatin** and **cisplatin**, both administered intravenously as solutions for infusion, with specific dosing regimens tailored to the study protocol. The trial is categorized as a Phase III trial, focusing on the therapeutic benefits of adjuvant therapy in the specified patient population.

The clinical trial involves the administration of **Carboplatin Kabi**, a **solution for infusion** with a concentration of 10 mg/ml. The active substance is **carboplatin**, a chemical compound, and the product is manufactured by Fresenius Kabi S.R.O. The medication is administered **intravenously**. The dosing regimen allows for a maximum daily dose of 2 units, with a total maximum dose of 6 units over a treatment period of up to 8 weeks. This product is classified under the ATC code L01XA02, indicating its role as a platinum-containing compound used in chemotherapy.

Another treatment used in the trial is **Cisplatin Ebewe**, also a **solution for infusion** with a concentration of 1 mg/ml. The active substance is **cisplatin**, a chemical compound, provided by EBEWE Pharma. This medication is administered **intravenously**. The dosing schedule permits a maximum daily dose of 40 mg/m², with a total maximum dose of 120 mg/m² over a treatment period of up to 8 weeks. Cisplatin is categorized under the ATC code L01XA01, denoting its use as a platinum-containing chemotherapeutic agent.

The trial also includes the use of **Carboplatin Accord**, a **solution for infusion** with a concentration of 10 mg/ml. The active substance is **carboplatin**, a chemical compound, produced by Accord Healthcare Polska Sp. z o.o. This medication is administered **intravenously**. The dosing regimen allows for a maximum daily dose of 2 units, with a total maximum dose of 6 units over a treatment period of up to 8 weeks. Similar to Carboplatin Kabi, this product is classified under the ATC code L01XA02, indicating its role as a platinum-containing compound used in chemotherapy.

The efficacy of the clinical trial will be assessed primarily through the measurement of **disease-free survival** (DFS) in patients with early-stage, intermediate-risk cervical cancer. The primary endpoint is defined as the time from randomization to the occurrence of disease recurrence or death from any cause, analyzed three years after the randomization of the last patient. The trial aims to determine if adjuvant therapy provides a DFS benefit following radical surgery. A total of 514 patients are required to achieve 80% power at a 5% significance level, with a non-inferiority margin of 5% using the Cox proportional hazards model.

Secondary endpoints include overall survival, pelvic disease-free survival, health-related quality of life assessed via a questionnaire, and treatment-related adverse events categorized according to the Common Terminology Criteria for Adverse Events v5.0. These parameters will be collected and analyzed at specified intervals throughout the trial duration. The trial is designed to ensure rigorous assessment of the therapeutic efficacy of adjuvant therapy in this patient population, with a comprehensive evaluation of both survival outcomes and quality of life impacts.