Feasibility of Intraoperative Fluorescence Imaging with cRGD-ZW800-1 in Identifying Laryngeal and Hypopharyngeal Squamous Cell Carcinoma

The primary objective of the STELLAR trial is to assess the **feasibility** of utilizing intraoperative fluorescence-imaging (FLI) to identify **laryngeal** and **hypopharyngeal cancer** during total laryngectomy or pharyngectomy. The feasibility is defined by achieving a tumor-to-background ratio (TBR) greater than 1.5. This is clinically relevant as it may enhance the precision of surgical interventions, potentially improving patient outcomes by ensuring more accurate tumor resection.

Secondary objectives include evaluating the sensitivity, specificity, and positive predictive value of FLI; assessing intraoperative changes in surgical management based on FLI; determining the FLI of excised cervical lymph nodes; examining the influence of previous radiotherapy on FLI performance; and monitoring adverse events and toxicity following intravenous injection with cRGD-ZW800-1. These objectives aim to provide comprehensive insights into the diagnostic and therapeutic utility of FLI in the surgical management of squamous cell carcinoma of the larynx and hypopharynx.

The clinical trial involves participants diagnosed with **squamous cell carcinoma of the larynx and hypopharynx**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a biopsy-proven diagnosis and be eligible for surgical resection of the tumor. The trial does not include a vulnerable population, and participants must have sufficient knowledge of the Dutch language to understand the informed consent form. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the feasibility of using **intraoperative fluorescence-imaging** (FLI) to identify **squamous cell carcinoma of the larynx and hypopharynx** during total laryngectomy or pharyngectomy. This study is structured as a **randomized, double-blind, controlled trial** and is categorized as a Phase I and Phase II integrated clinical trial. The trial is expected to commence on December 1, 2024, and conclude by December 1, 2025. Participants will be administered the investigational product, cRGD-ZW800-1, via **intravenous infusion**. The primary endpoint is to achieve a tumor-to-background ratio (TBR) greater than 1.5, which is considered feasible, and to assess the number of clear resection margins.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as biopsy-proven squamous cell carcinoma, age of 18 years or older, and sufficient understanding of the Dutch language. Written informed consent is required. Follow-up visits will be scheduled to monitor the administration of the fluorescent tracer and assess the imaging results. The end-of-study visit will evaluate the overall outcomes and any adverse events. The expected duration of participant involvement is approximately one year, aligning with the trial's overall timeline. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse reactions to the investigational product.

The clinical trial involves the administration of the experimental medication **cRGD-ZW800-1**, which is utilized as a **fluorescent tracer**. This investigational product is formulated for **intravenous infusion** and is not a pediatric formulation. The active substance, **CRGD-ZW800-1**, is derived from a protein of other origin. The administration of cRGD-ZW800-1 is conducted via intravenous infusion, although specific dosage and frequency details are not provided in the available data. The investigational product is intended to facilitate fluorescence-guided surgery in patients with laryngeal and hypopharyngeal cancer, aiming to achieve a tumor-to-background ratio greater than 1.5, which is considered feasible for the study's objectives.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are explicitly mentioned. The focus remains on the feasibility of using intraoperative fluorescence imaging to enhance surgical outcomes. Participant compliance with the administration protocol is monitored, although specific compliance measures are not detailed in the provided information. The trial is conducted under the auspices of Erasmus MC, with the investigational product being authorized for use in this specific clinical context.

Efficacy in this clinical trial will be assessed primarily through the evaluation of the **tumor-to-background ratio (TBR)** of laryngeal or pharyngeal tumors using fluorescence imaging after the administration of cRGD-ZW800-1. A TBR greater than 1.5 is defined as feasible, serving as the primary endpoint for the first work package (WP-1). Additionally, the primary endpoint for the second work package (WP-II) is the number of clear resection margins achieved during surgery. These endpoints will be measured and analyzed to determine the feasibility and effectiveness of intraoperative fluorescence imaging in identifying laryngeal and hypopharyngeal cancer during total laryngectomy or pharyngectomy.