Phase III Randomized Trial of Induction Chemotherapy with Carboplatin and Paclitaxel Followed by Concurrent Chemoradiotherapy in Cervical Cancer with Para-aortic Lymph Node Involvement

The primary objective of this study is to evaluate whether **induction chemotherapy** with three cycles of Carboplatin and Paclitaxel, followed by standard treatment (concurrent chemoradiotherapy), improves overall survival compared to standard treatment alone in patients with locally advanced **cervical cancer** with para-aortic lymph node involvement. This is clinically relevant as it aims to enhance survival outcomes in a patient population with a significant disease burden.

Secondary objectives include:

• Assessing and comparing the effect of induction chemotherapy followed by standard treatment versus standard treatment alone on tumor response, progression-free survival, site of disease recurrence, and health-related quality of life.
• Evaluating local and para-aortic lymph node response after induction chemotherapy.
• Assessing the safety of induction chemotherapy followed by standard treatment in this patient population.

The clinical trial focuses on evaluating treatment efficacy in patients with **cervical cancer**. The study population comprises exclusively female participants, as male subjects are not included. Participants are adults aged 18 years and older, with no upper age limit specified. The trial 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 2, and must meet specific health criteria, including normal renal, liver, and hematological function. The trial population was selected based on the presence of para-aortic lymph node involvement, determined through specific diagnostic methods. Lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is a **phase III**, multicenter, parallel-group randomized, controlled study designed to evaluate the efficacy of induction chemotherapy followed by standard concurrent chemoradiotherapy in patients with locally advanced **cervical cancer** with para-aortic lymph node involvement. The trial employs a two-arm design, with participants randomly assigned in a 1:1 ratio to receive either the investigational treatment or the standard treatment alone. The investigational treatment consists of three cycles of induction chemotherapy with **Carboplatin** and **Paclitaxel**, followed by standard concurrent chemoradiotherapy. The primary objective is to assess whether this regimen improves overall survival compared to standard treatment alone. The trial is expected to conclude by January 17, 2028, with recruitment having commenced on July 17, 2020.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, performance status, and specific cancer staging. Subsequent visits will include regular follow-up assessments to monitor treatment response and adverse events, as well as to collect data on secondary endpoints such as progression-free survival and health-related quality of life. The end-of-study visit will occur after the completion of the treatment regimen and final assessments. The expected duration of participant involvement is approximately three months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent.

The clinical trial involves the administration of **PACLITAXEL KABI**, a solution for infusion with a concentration of 6 mg/ml. The active substance in this medication is **paclitaxel**, a chemical compound classified under the ATC code L01CD01. The pharmaceutical form is a solution to be diluted for intravenous infusion. The maximum daily dose is 175 mg/m², with a total maximum dose of 11025 mg/m² over a treatment period of up to 3 cycles. The administration route is via intravenous infusion, and the product is manufactured by Fresenius Kabi France S.A.S. Participant compliance with the dosing schedule will be monitored throughout the trial.

Another experimental medication used in the trial is **Carboplatin Accord Healthcare**, a solution for infusion with a concentration of 10 mg/ml. The active substance is **carboplatin**, also a chemical compound, and it is classified under the ATC code L01XA02. This medication is also administered as a solution to be diluted for intravenous infusion. The maximum daily dose is 5 mg/ml, with a total maximum dose of 315 mg/ml over a treatment period of up to 3 cycles. The administration route is intravenous infusion, and the product is manufactured by Accord Healthcare B.V. Compliance with the dosing schedule will be closely monitored to ensure adherence to the treatment protocol.

The trial aims to evaluate the efficacy of induction chemotherapy with these two medications, followed by standard concurrent chemoradiotherapy, in improving overall survival in patients with locally advanced cervical cancer with para-aortic lymph node involvement. The study does not include any non-experimental treatments such as placebo or comparator treatments, as the focus is on the experimental regimen's impact on patient outcomes.

Efficacy in the clinical trial titled "Induction chemotherapy followed by standard concurrent chemoradiotherapy in cervical cancer with para-aortic lymph node involvement: A phase III, multicenter, parallel-group randomized, controlled trial - ONCOCOL-01" will be assessed using both primary and secondary endpoints. The primary endpoint is **overall survival**, defined as the time from the date of randomization to the date of death from any cause. This will provide a direct measure of the treatment's impact on patient longevity.

Secondary endpoints include several parameters: tumor response at the end of standard treatment, assessed by investigator evaluations according to RECIST 1.1 and PERCIST 1.0 criteria; progression-free survival, defined as the time from randomization to disease progression or death; and the site of disease recurrence, categorized as local, pelvic, para-aortic lymph nodes, or distant. Additionally, health-related quality of life will be evaluated using the EORTC QLQ-C30 questionnaire and the QLQ-CX24 module. Adverse events will be monitored from the first administration of the study treatment, assessed according to the NCI-CTCAE version 5.0.