Phase II Randomized Trial Evaluating Cisplatin, 5-Fluorouracil, and Docetaxel in Locally Advanced Squamous Cell Carcinoma

The primary objective of this phase II randomized trial is to evaluate the **effectiveness** of the combination of cisplatin, 5-fluorouracil, and docetaxel at adapted doses (TPFm) in patients with locally advanced squamous cell carcinoma. The focus is on assessing the response to treatment without associated toxicity, which is clinically relevant as it aims to optimize therapeutic outcomes while minimizing adverse effects in this patient population.

Secondary objectives include:

• Overall survival
• Progression-free survival
• Local and/or locoregional control
• Laryngeal preservation
• Distant metastases (incidence and survival)
• Toxicities of complementary treatment to induction treatment
• Compliance with induction treatment
• Assessment of quality of life
• Hospitalization or extension of hospitalization for treatment toxicity
• Length of hospitalization during induction treatment

The clinical trial involves participants diagnosed with **locally advanced squamous cell carcinoma** of the oral cavity, oropharynx, hypopharynx, or larynx. The study population includes both male and female subjects aged between 18 and 75 years, with a performance status of 0 or 1 according to WHO criteria. Participants are required to have at least one measurable lesion as per RECIST 1.1 criteria and must be able to receive the TPF regimen based on well-defined criteria. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are expected to have an estimated life expectancy of at least three months and should not have been previously treated for head and neck cancer. The selection process for the trial population is based on specific inclusion criteria, ensuring that individuals with inoperable tumors or those for whom surgery would be mutilating are considered. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is designed as a **randomized**, non-comparative, phase II study evaluating the effectiveness of a chemotherapy regimen consisting of **cisplatin**, **5-fluorouracil**, and **docetaxel** at adapted doses in patients with locally advanced squamous cell carcinoma. The primary objective is to assess the response to treatment without toxicity. The trial is expected to commence on March 25, 2024, and conclude by August 6, 2024, with an estimated duration of 12 months for participant involvement. The study will include several key phases, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically proven squamous cell carcinoma, age between 18 and 75 years, and a performance status of 0 or 1 according to WHO standards.

Participants will be randomly assigned to receive the chemotherapy regimen via **intravenous infusion**. The treatment period will last up to 12 weeks, with follow-up visits scheduled at regular intervals to monitor the rate of patient success at 8 weeks, overall survival, progression-free survival, and other secondary endpoints. These follow-up visits will also assess the rate of patients in local and/or locoregional control of the disease, the rate of larynx preservation, and the toxicity of the treatment. The end-of-study visit will evaluate the overall outcomes and any adverse events experienced by the participants.

Participants are expected to remain in the study for the full duration unless conditions arise that necessitate early termination, such as significant adverse reactions or disease progression. The trial will adhere to strict protocols to ensure the safety and well-being of all participants, with hospitalization or extension of hospitalization being considered for toxicity linked to the treatments under study. The quality of life will be assessed using the EORTC QLQ-C30 and EORTC H&N35 questionnaires. The trial's design and procedures are structured to provide comprehensive data on the efficacy and safety of the chemotherapy regimen in the specified patient population.

The clinical trial involves the administration of **DOCETAXEL**, marketed as DOCETAXEL HOSPIRA 10 mg/mL, solution à diluer pour perfusion. This pharmaceutical is presented as a **solution for infusion** and is administered via **intravenous infusion**. The maximum daily dose is 40 mg/m², with a total maximum dose of 240 mg/m² over a treatment period of up to 12 weeks. The product is classified as an antineoplastic agent and is manufactured by Pfizer Holding France. Participant compliance is monitored through regular assessments of infusion administration and dosage adherence.

**FLUOROURACIL**, available as Fluorouracil Accord 50 mg/ml Injektions-/ Infusionslösung, is another experimental medication used in this trial. It is provided as a **solution for injection/infusion** and administered intravenously. The maximum daily dose is 1000 mg/m², with a total maximum dose of 6000 mg/m² over a 12-week period. This cytostatic antineoplastic agent belongs to the antimetabolite class and is produced by Accord Healthcare B.V. Compliance is ensured through scheduled dosing and infusion records.

Another formulation of **FLUOROURACIL** is used, marketed as Fluorouracil Accord 50 mg/ml διάλυμα για ένεση/έγχυση. This product is also a **solution for injection/infusion** administered intravenously. The maximum daily dose is 750 mg/m², with a total maximum dose of 2250 mg/m² over a 9-week period. It is manufactured by Accord Healthcare S.L.U. and participant adherence is tracked through infusion logs and dosage monitoring.

**CISPLATIN**, marketed as Cisplatin Accord 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung, is included in the trial as a **solution for infusion**. It is administered via intravenous infusion with a maximum daily dose of 40 mg/m² and a total maximum dose of 240 mg/m² over a 12-week period. This cytostatic antineoplastic is produced by Accord Healthcare B.V. Compliance is monitored through infusion schedules and dosage verification.

Another formulation of **CISPLATIN** is used, known as Cisplatine Hospira 100 mg/100 ml Onco-Tain solution injectable. This product is a **solution for injection** administered intravenously. The maximum daily dose is 75 mg/m², with a total maximum dose of 225 mg/m² over a 9-week period. It is manufactured by Hospira Benelux. Participant adherence is ensured through detailed infusion records and dosage checks.

In this trial, the combination of these medications is evaluated for their effectiveness in treating locally advanced squamous cell carcinoma, with a focus on response to treatment and minimizing toxicity. The trial does not include any non-experimental treatments such as placebo or standard-of-care therapy. Compliance monitoring is a critical component, involving regular assessments of infusion administration and adherence to dosing schedules.

The efficacy of the clinical trial will be assessed using a combination of primary and secondary endpoints. The primary endpoint is the rate of patient success at 8 weeks. Secondary endpoints include overall survival, progression-free survival, and metastasis-free survival. Overall survival is defined as the time from randomization to death from any cause, with data censored at the last known follow-up if death is not reported. Progression-free survival is measured from randomization to the first evidence of disease progression, death, or last follow-up without progression. Metastasis-free survival is defined from randomization to the first evidence of metastatic progression or death.

Additional secondary endpoints include the rate of patients achieving local and/or locoregional control of the disease at week 8 ± 3 days, the rate of patients with larynx preservation, and the toxicity of complementary treatment to induction treatment. The trial will also evaluate the rate of patients who complete the entire induction treatment and the complementary treatment, as well as hospitalization or extended hospitalization due to treatment-related toxicity. Quality of life will be assessed using the EORTC QLQ-C30 and EORTC H&N35 questionnaires.