Comparison of Weekly Low-Dose Versus Three-Weekly High-Dose Cisplatin in Chemoradiation for Sarcopenic Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma

The primary objective of this study is to evaluate whether the administration of weekly low dose **cisplatin** enhances compliance with the planned chemotherapy regimen in patients with **locally advanced head and neck squamous cell carcinoma** (LA-HNSCC) who exhibit low skeletal muscle mass (SMM). The goal is to achieve a level of compliance comparable to that observed in patients receiving high dose cisplatin every three weeks who do not have low SMM. This is clinically relevant as improved compliance could potentially lead to better treatment outcomes and reduced toxicity in this specific patient population.

The clinical trial involves participants diagnosed with **locally advanced head and neck squamous cell carcinoma**. The study population includes both male and female subjects, aged eighteen years and older. Participants are required to have a sufficient understanding of Dutch and the medical implications to provide informed consent. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include individuals considered eligible and planned for primary cisplatin chemoradiotherapy by their treating physician. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **cisplatin** in patients with locally advanced head and neck squamous cell carcinoma. The study employs a randomized, controlled, double-blind methodology to compare the compliance rates between weekly low-dose and three-weekly high-dose cisplatin regimens. The trial is expected to span from July 2021 to November 2027, with participant involvement lasting up to 7 weeks, depending on individual treatment response and tolerance.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as age (18 years or older), understanding of Dutch, and the ability to provide informed consent. Following the inclusion visit, participants will receive intravenous administration of cisplatin, with dosing adjusted according to the assigned regimen. Follow-up visits will be scheduled to monitor compliance, adverse events, and any necessary dose adjustments. The primary endpoint is the compliance rate, defined by the absence of chemotherapy dose-limiting toxicity (CDLT), which includes any toxicity leading to a dose reduction of 50% or more, treatment postponement of 4 days or more, or termination after the first or second cycle.

Secondary endpoints include adverse events, cumulative cisplatin dose, time to recurrence, 2-year overall survival, costs, quality of life, and patient preference. The end-of-study visit will assess the overall outcomes and gather final data on the primary and secondary endpoints. Participants may be withdrawn from the study early if they experience significant toxicity, fail to comply with the treatment protocol, or withdraw consent. The trial aims to provide insights into optimizing chemotherapy regimens for patients with low skeletal muscle mass, potentially improving compliance and treatment outcomes.

The clinical trial involves the administration of **Cisplatin**, marketed as Cisplatin Accord Healthcare 1 mg/ml, which is a **solution for infusion**. This experimental medication is provided in the form of a concentrate for solution for infusion and is intended for **intravenous use**. The active substance, **cisplatin**, is of chemical origin. The dosing regimen for this trial includes a maximum daily dose of 40 mg/m² and a maximum total dose of 280 mg/m² over a treatment period of 7 days. The trial aims to compare the effects of low-dose weekly administration versus high-dose administration every three weeks in patients with head and neck squamous cell carcinoma.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of the experimental medication, **cisplatin**, to evaluate its efficacy and compliance in the specified patient population. Participant compliance will be monitored throughout the trial to ensure adherence to the dosing schedule and to assess the impact of the treatment regimen on patient outcomes.

Efficacy in this clinical trial will be assessed primarily through the measurement of compliance to the proposed cisplatin chemotherapy scheme in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) and low skeletal muscle mass (SMM). The primary endpoint is defined as the compliance rate, specifically the absence of **CDLT** (chemotherapy dose-limiting toxicity). CDLT is characterized by any toxicity that results in a cisplatin dose reduction of 50% or more, a treatment postponement of 4 days or more, or a definitive termination of cisplatin after the first or second cycle of therapy.

Secondary efficacy parameters include adverse events and toxicity, cumulative cisplatin dose, time to recurrence, 2-year overall survival, costs, quality of life, and patient preference. The main oncological outcomes are time to recurrence and survival. Clinically relevant treatment-related toxicity parameters, including significant toxicity (grade 3 or 4) that leads to treatment de-escalation or termination, will be documented by the treating medical oncologist. These assessments will provide a comprehensive evaluation of the treatment's efficacy and its impact on patient outcomes.