Evaluation of Carboplatin, Paclitaxel, and Cetuximab in Second-Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

The primary objective of this study is to evaluate the **objective response rate** of the combination therapy of Carboplatin, Paclitaxel, and Cetuximab (PCC) in patients with second-line recurrent or metastatic **head and neck squamous cell carcinoma** following the failure of Pembrolizumab with or without chemotherapy. This objective is clinically relevant as it aims to determine the efficacy of PCC in a patient population with limited treatment options, potentially offering an alternative therapeutic strategy.

Secondary objectives include assessing:

• **Progression-free survival**, which measures the length of time during and after treatment that a patient lives with the disease without it worsening.
• **Overall survival**, which evaluates the duration of survival of patients from the start of treatment.
• **Duration of response**, which examines the length of time the disease responds to treatment without progression.
• **Safety**, focusing on the adverse effects and tolerability of the treatment regimen.
• **Quality of life**, assessing the impact of the treatment on the patients' overall well-being and daily functioning.

The clinical trial involves participants diagnosed with **head and neck squamous cell carcinoma**, specifically targeting individuals with second-line recurrent or metastatic conditions following the failure of Pembrolizumab treatment, with or without chemotherapy. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a documented progression of a measurable tumor target according to RECIST 1.1, with cytological or histological confirmation of invasive squamous cell carcinoma in specified locations such as the oral cavity, oropharynx, larynx, or hypopharynx. Cancers of unknown primary in the head and neck are also accepted. The trial excludes vulnerable populations and focuses on individuals with an ECOG Performance Index of 0, 1, or 2, and a life expectancy of at least 12 weeks. Participants must have a chemotherapy-free interval of at least 3 months and be ineligible for curative surgical treatment or radiotherapy. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the **objective response rate** of a combination therapy involving **cetuximab**, **paclitaxel**, and **carboplatin** in patients with second-line recurrent or metastatic **head and neck squamous cell carcinoma** following the failure of pembrolizumab with or without chemotherapy. This is a Phase 4, randomized, double-blind, controlled trial. The trial is expected to commence on September 15, 2024, and conclude by September 15, 2029, with a maximum treatment period of 16 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, documented tumor progression, and performance status. The inclusion criteria require participants to be 18 years or older, have a measurable tumor progression according to RECIST 1.1, and have a cytological or histological confirmation of invasive squamous cell carcinoma of the head and neck. The trial will accept cancers of unknown primary of the head and neck and requires a chemotherapy-free interval of at least three months. The screening visit will also assess the patient's life expectancy, which must be at least 12 weeks.

Following the inclusion visit, participants will receive the investigational treatment through **intravenous infusion**. Regular follow-up visits will be scheduled to monitor the patient's response to the treatment, collect data on progression events, and assess any treatment-emergent adverse events according to CTCAE V5.0 criteria. The primary endpoint is the number of patients achieving an objective response within 12 months. Secondary endpoints include progression events, overall survival status, and the time from the first documented response to subsequent progression or death.

The end-of-study visit will occur after the completion of the treatment period or upon early termination. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent by the participant. The expected length of participant involvement is up to 16 weeks, with additional follow-up extending beyond 12 months to collect long-term data on survival and quality of life using the QLQ-C30 and QLQ-HN35 questionnaires.

The clinical trial involves the administration of **Erbitux** 5 mg/mL, a **solution for infusion** containing the active substance **cetuximab**. Cetuximab is a protein-based therapeutic agent, specifically classified as a protein of other origin. The pharmaceutical form is a solution for infusion, and it is administered via the **intravenous** route. The maximum daily dose is 400 mg/m², with a total maximum dose of 4150 mg/m² over a treatment period of up to 16 weeks. The administration schedule and participant compliance are monitored to ensure adherence to the dosing regimen.

Another treatment used in the trial is **PACLITAXEL AHCL** 6 mg/mL, a solution to be diluted for infusion, containing the active substance **paclitaxel**. Paclitaxel is a chemical-based therapeutic agent. The pharmaceutical form is a solution for infusion, administered through **intravenous infusion**. The maximum daily dose is 80 mg/m², with a total maximum dose of 1280 mg/m² over a treatment period of up to 16 weeks. The dosing schedule is carefully monitored to ensure participant compliance and safety.

The trial also includes the administration of **CARBOPLATINE HOSPIRA** 10 mg/mL, a solution injectable for infusion, containing the active substance **carboplatin**. Carboplatin is a chemical-based therapeutic agent. The pharmaceutical form is a solution for injection/infusion, administered via the **intravenous** route. The maximum daily dose is 220 mg, with a total maximum dose of 3520 mg over a treatment period of up to 16 weeks. Compliance with the dosing schedule is monitored to ensure the safety and efficacy of the treatment.

All treatments are administered in accordance with the study protocol, and participant compliance is monitored through regular assessments and documentation. The trial aims to evaluate the objective response rate of the combination therapy in patients with second-line recurrent or metastatic squamous cell carcinoma of the head and neck after the failure of pembrolizumab with or without chemotherapy.

Efficacy in this clinical trial will be assessed primarily through the **objective response rate** of the treatment regimen consisting of Carboplatin, Paclitaxel, and Cetuximab (PCC) in patients with second-line recurrent or metastatic squamous cell carcinoma of the head and neck. The primary endpoint is the number of patients who achieve an objective response within 12 months. Secondary endpoints include the collection of progression events such as loco-regional progression, metastatic progression, or death from any cause beyond 12 months of patient participation, as well as the patient's condition (alive, deceased, or lost to follow-up) beyond 12 months. The time from the date of first documented response to the date of first subsequent progression or death from any cause will also be measured. Additionally, the incidence of treatment-emergent adverse events and serious adverse events will be evaluated according to CTCAE V5.0 criteria, along with the administration of the QLQ-C30 and QLQ-HN35 questionnaires to assess patient-reported outcomes.