Evaluation of Swallowing Outcomes and Quality of Life in Advanced Oropharyngeal Cancer Patients Undergoing Prophylactic Versus Reactive PEG Tube Placement with Cisplatin and Drug Combination

The primary objective of this study is to assess and compare the **subjects reported outcomes** in terms of swallowing, utilizing the MD Anderson Dysphagia Inventory (MDADI), six months following the completion of chemoradiotherapy in patients with advanced head and neck cancer. Participants are randomized into two groups: those receiving prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement and those receiving reactive PEG tube placement. This evaluation is clinically relevant as it aims to determine the optimal timing for PEG tube placement to improve swallowing outcomes and quality of life in patients undergoing definitive chemoradiotherapy for oropharyngeal cancer.

Secondary objectives include:

• Assessing health-related quality of life (HRQOL) using EORTC QLQ-C30, EORTC QLQ-H&N43 module, and FACT-HN.
• Evaluating chemoradiotherapy (CRT) related toxicities and complications associated with PEG tube placement.
• Investigating the impact of nutritional status on survival and toxicity outcomes.
• Assessing clinical tumor response post-treatment.
• Evaluating loco-regional control, distant recurrence/progression, second primary occurrences, disease-free survival, disease-specific survival, and overall survival.
• Examining the influence of HPV and tobacco smoking on these secondary endpoints.
• Determining the cost-effectiveness of each treatment strategy.
• Conducting clinical validation of cancer prediction models available at www.predictcancer.org.

The clinical trial focuses on individuals diagnosed with **oropharyngeal cancer**, specifically targeting those with newly diagnosed, histologically confirmed primary squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, and nasopharyngeal carcinoma. The study population includes both male and female participants aged 18 years and older. Participants are required to have adequate bone marrow, liver, and renal function, as well as a performance status of 2 or less on the ECOG scale. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants must be candidates for curative intent radiotherapy and systemic treatment, with no prior or current anticancer treatment for head and neck cancer. Lifestyle considerations such as diet and physical activity are not detailed in the available data. The trial population was selected based on specific inclusion criteria, including the ability to understand and complete questionnaires, and the availability of diagnosis biopsy and HPV/p16 testing results at the time of screening. The trial includes a vulnerable population, and both genders are represented. The sponsor has not provided information on the total number of participants.

The clinical trial is designed to evaluate patient-reported outcomes in terms of swallowing and quality of life following prophylactic versus reactive percutaneous endoscopic gastrostomy tube placement in patients with advanced **oropharyngeal cancer** undergoing definitive chemoradiotherapy. This is a randomized, double-blind, controlled trial with an estimated duration from August 2021 to November 2025. Participants will be randomly assigned to either the prophylactic or reactive PEG tube group, with the primary endpoint being the global MD Anderson Dysphagia Inventory (MDADI) score assessed six months post-treatment.

The trial will involve several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, adequate organ function, and performance status. Participants must complete all necessary screening procedures within 15 days prior to randomization. Follow-up visits will be scheduled to monitor patient-reported outcomes, adverse events, and treatment efficacy. The end-of-study visit will occur after the final assessment of the primary endpoint at six months post-treatment.

Participant involvement is expected to last approximately four years, from recruitment to the final follow-up. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial will utilize **cisplatin** as the primary investigational product, administered intravenously, with a maximum daily dose of 100 mg/m² and a total dose not exceeding 200 mg/m² over a seven-day treatment period. Auxiliary products such as **barium sulfate**, **iomeprol**, and **fludeoxyglucose (18F)** will be used for diagnostic and supportive purposes, with specific dosing and administration routes as per protocol requirements.

The clinical trial involves the administration of **Cisplatin**, a **concentrate for solution for injection**. This experimental medication is administered **intravenously**. The dosage is calculated based on body surface area, with a maximum daily dose of **100 mg/m²** and a total maximum dose of **200 mg/m²** over a treatment period of up to **7 days**. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

**Barium Sulfate** is used as an auxiliary treatment in the study. It is provided in the form of an **oral suspension** and is administered via **oral use**. The maximum daily dose is **50 mg/ml**, with a total maximum dose of **250 mg/ml** over a period of **7 days**. This substance is utilized to assist in diagnostic imaging procedures as part of the trial protocol.

Another auxiliary treatment, **Iomeprol**, is administered as a **solution for injection**. This substance is delivered **intravenously** with a maximum daily dose of **400 mg/ml** and a total maximum dose of **1200 mg/ml** over a **7-day** treatment period. Iomeprol is used to enhance imaging quality during diagnostic procedures within the trial.

**Fludeoxyglucose (18F)**, also an auxiliary treatment, is provided as a **solution for injection** and administered **intravenously**. The maximum daily dose is **400 MBq**, with a total maximum dose of **400 MBq** over a **7-day** period. This radiopharmaceutical is employed for positron emission tomography (PET) imaging to assess metabolic activity as part of the study's diagnostic evaluations.

Efficacy in this clinical trial will be assessed primarily through the global MD Anderson Dysphagia Inventory (MDADI) score, evaluated at 6 months following the completion of chemoradiotherapy treatment. This endpoint is designed to measure the impact of treatment on swallowing function in patients with advanced head and neck cancer. Secondary efficacy assessments will include patient-reported outcomes using self-administered questionnaires such as the Health-Related Quality of Life (HRQOL) instruments EORTC QLQ-C30 and EORTC QLQ-H&N43 module, and the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN). Additionally, oral-oropharyngeal toxicity will be evaluated using the Oral Mucositis Weekly Questionnaire for Head and Neck cancer (OMWQ-NH), and salivary toxicity will be assessed via the xerostomia questionnaire.

Further secondary endpoints will involve the incidence, type, and severity of adverse events (AEs) and serious adverse events (SAEs) as per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Radiotherapy-related AEs will be evaluated using the Radiation Therapy Oncology Group (RTOG) and European Organisation for Research and Treatment of Cancer (EORTC) scores. The impact of nutritional status on survival and toxicity outcomes will be assessed using the Global Leadership Initiative on Malnutrition (GLIM) criteria, along with biomarkers such as C-reactive protein (CRP), albumin, and pre-albumin levels. Tumor response will be measured at 3 months post-treatment using Dual-Energy Computed Tomography (DECT) and Positron Emission Tomography-Computed Tomography (PET-CT). Additional outcomes include loco-regional control (LRC), distant recurrence/distant progression (DR/DP), second primary (SP), disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS).