Assessment of Somatostatin Receptor 2 Expression in Nasopharyngeal Carcinoma Using [68Ga]Ga-DOTA-TOC PET/CT Imaging: A Pilot Study

The primary objective of this study is to determine the **feasibility** of assessing tumor somatostatin receptor 2 (SSTR2) expression in patients with Epstein-Barr virus (EBV)-associated **nasopharyngeal carcinoma** (NPC) in a non-endemic region through repeat [68Ga]Ga-DOTA-TOC PET imaging. This is clinically relevant as it may enhance the selection of targeted therapies for NPC, potentially improving treatment outcomes.

Secondary objectives include: - Determining [68Ga]Ga-DOTA-TOC uptake in the primary tumor and lymph node metastases in patients with EBV-related NPC at baseline and early after the start of curative intent treatment, which consists of chemoradiotherapy (CRT) with or without induction chemotherapy. - Evaluating the distribution of [68Ga]Ga-DOTA-TOC in normal tissues and organs in NPC patients. - Comparing baseline tumor [68Ga]Ga-DOTA-TOC uptake with SSTR2 expression determined by immunohistochemistry (IHC).

The clinical trial involves participants diagnosed with **nasopharyngeal carcinoma** (NPC), specifically those with Stage IB-IVA NPC as per the AJCC 9th edition, and Epstein-Barr virus (EBV) positive status. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a planned treatment regimen involving either induction chemotherapy or concurrent chemoradiotherapy (CRT) without induction chemotherapy. The trial does not include a vulnerable population. Participants must have archival tumor tissue available and women of childbearing potential must have a negative serum pregnancy test at screening. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize the ability and willingness to comply with all protocol-required procedures, and informed consent is mandatory. 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 assessing tumor somatostatin receptor 2 (SSTR2) expression in patients with **nasopharyngeal carcinoma** (NPC) using [68Ga]Ga-DOTA-TOC PET imaging. This study is a proof-of-concept pilot trial, employing a randomized, double-blind, controlled design. The trial is scheduled to commence on September 22, 2025, with an estimated completion date of December 1, 2026. The trial will involve multiple study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as stage IB-IVA NPC, Epstein-Barr virus positivity, and other protocol-specific requirements. Participants will undergo a series of follow-up visits to monitor the uptake of [68Ga]Ga-DOTA-TOC and assess the primary endpoint, which is the visualization and quantification of tumor uptake in at least seven out of ten patients, with repeat imaging completed in at least six patients. Secondary endpoints include the evaluation of SUVpeak values of primary tumors and lymph node metastases, as well as SUVmean values in normal tissues. The end-of-study visit will conclude the participant's involvement, which is expected to last until the trial's completion. Conditions that may lead to early termination from the study include non-compliance with protocol procedures or adverse events that compromise participant safety. The trial aims to provide insights into the potential of [68Ga]Ga-DOTA-TOC PET imaging as a tool for improved therapy selection and targeted treatment in NPC. Participants will receive the investigational product, 68Ga-Dotatoc, administered via intravenous injection, with the study being conducted under the authorization of the relevant regulatory bodies. The trial is not categorized as low intervention and is classified as a phase 9 trial, emphasizing its exploratory nature in the context of nasopharyngeal carcinoma treatment.

The clinical trial involves the use of the experimental medication **68Ga-Dotatoc**, which is a **solution for injection**. The active substance in this medication is **gallium (68Ga) edotreotide**, a chemical compound. The pharmaceutical form of 68Ga-Dotatoc is a solution specifically designed for intravenous use. The administration of this medication is conducted via intravenous injection, although the specific dosage and frequency of administration are not detailed in the provided data. The medication is not formulated for pediatric use and is not classified as an orphan drug. The trial aims to assess the feasibility of using 68Ga-Dotatoc for imaging purposes in patients with nasopharyngeal carcinoma.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The focus is solely on the administration of 68Ga-Dotatoc for the purpose of imaging. The trial does not specify any additional information regarding dosing schedules or participant compliance monitoring. The study is authorized and conducted by the University Medical Center Groningen, with the trial status being authorized in the Netherlands. The trial's main objective is to evaluate the feasibility of assessing tumor somatostatin receptor 2 expression in patients with Epstein-Barr virus-associated nasopharyngeal carcinoma using 68Ga-Dotatoc PET imaging.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint involves the feasibility of using **[68Ga]Ga-DOTA-TOC PET imaging** to visualize and quantify tumor uptake in patients with Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). This will be considered feasible if tumor uptake can be visualized and quantified in at least seven out of ten patients, with repeat imaging completed in at least six patients.

Secondary endpoints include the measurement of SUVpeak values of primary tumors and lymph node metastases on the pre-treatment scan, as well as SUVmean values in normal tissues and organs, with healthy lymph nodes defined by SUVpeak. Additionally, tumor somatostatin receptor 2 (SSTR2) expression will be determined by immunohistochemistry (IHC).