Assessment of Somatostatin Receptor Expression via 68Ga-DOTATOC PET in Patients with Metastatic Breast Cancer

The primary objective of this study is to evaluate the presence of lesions overexpressing **somatostatin receptors** (SST2) using 68Ga-DOTATOC PET scans in patients with metastatic breast cancer. This is clinically relevant as it may provide insights into the extent of receptor expression, which could influence treatment decisions and prognostic assessments in this patient population.

Secondary objectives include:

• Assessing the distribution of SST2 receptor overexpression using 68Ga-DOTATOC PET compared to lesions identified with 18F-FDG PET.
• Evaluating the proportion of disease with SST2 receptor overexpression in comparison to known metastatic disease on 18F-FDG PET.
• Assessing SST2 receptor expression within lesions based on different metastatic sites.
• Correlating the metabolic activity of lesions on 18F-FDG PET with SST2 receptor expression on 68Ga-DOTATOC PET by lesion and by patient.
• Evaluating clinico-biological, histological, and imaging predictive factors for SST2 receptor overexpression on 68Ga-DOTATOC PET by patient and by lesion.

The clinical trial focuses on **breast cancer** and involves a study population exclusively composed of female participants. The age range of the participants is above 18 years, with no upper age limit specified. The trial does not include male subjects or any vulnerable populations. Participants are required to have metastatic breast cancer and must have completed at least one line of systemic treatment for metastatic breast cancer. The trial population was selected based on specific criteria, including the presence of ER+HER2- primary lesions and identifiable metastatic lesions in the liver and/or bones via 18F-FDG PET scans. Additionally, participants must have at least 10 secondary lesions identifiable by 18F-FDG PET and no therapeutic modifications between the 18F-FDG PET and the 68Ga-DOTATOC PET scans. 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 expression of somatostatin receptors in **metastatic breast cancer** patients using DOTATOC-68Ga PET scans. This is a Phase 4, exploratory trial with a randomized, double-blind, controlled design. The trial is expected to commence recruitment on September 1, 2024, and conclude by September 1, 2026. Participants will be involved in the study for a maximum treatment period of one day, with the primary endpoint being the identification of metastatic lesions exhibiting SST2 receptor overexpression as determined by a Krenning score of ≥2 on the 68Ga-DOTATOC PET scan.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age over 18, prior systemic treatment for metastatic breast cancer, and identifiable metastatic lesions on 18F-FDG PET scans. Participants must also provide written informed consent. The inclusion visit will be followed by the administration of the investigational product, SomaKit TOC, which contains the active substance **edotreotide** and is administered intravenously as a solution for injection. Follow-up visits will include PET scans to assess the intensity of lesion uptake and quantify disease volume, comparing 68Ga-DOTATOC PET results with 18F-FDG PET results.

The end-of-study visit will involve a comprehensive collection of clinico-biological and imaging data. Participants may be terminated early from the study if they experience adverse reactions, fail to comply with study procedures, or withdraw consent. The trial aims to provide valuable insights into the potential of 68Ga-DOTATOC PET scans in assessing receptor expression in metastatic breast cancer, contributing to the optimization of diagnostic and therapeutic strategies.

The clinical trial involves the use of **SomaKit TOC 40 micrograms kit for radiopharmaceutical preparation** as the experimental medication. This product is formulated as a **solution for injection** and is intended for intravenous administration. The active substance in this preparation is **edotreotide**, a chemically synthesized compound. The maximum daily and total dose of edotreotide is 40 micrograms, with a treatment period limited to a single day. The product is not a pediatric formulation and is manufactured by Advanced Accelerator Applications. The pharmaceutical form is specifically designed for radiopharmaceutical preparation, ensuring precise delivery and efficacy in the clinical setting.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for use in this study. The focus is solely on the evaluation of the expression of somatostatin receptors using DOTATOC-68Ga PET scans in patients with metastatic breast cancer. The administration of the experimental medication is monitored to ensure compliance with the dosing schedule, and the intravenous route is chosen to facilitate optimal absorption and distribution of the radiopharmaceutical agent. The trial does not include any additional medications or interventions beyond the specified experimental treatment.

Efficacy in this clinical trial will be assessed through the evaluation of **somatostatin receptor** expression in patients with metastatic breast cancer using DOTATOC-68Ga PET scans. The primary endpoint is the identification of metastatic lesions exhibiting overexpression of SST2 receptors, as determined by a Krenning score of 2 or higher on the 68Ga-DOTATOC PET scan. Secondary endpoints include lesion-specific analysis of uptake intensity using the Krenning score and PET quantification parameters, quantification of disease volume per patient with SST2 receptor overexpression compared to metabolic volume on 18F-FDG PET, and site-specific analysis of lesion uptake intensity. Additionally, comparisons will be made between 68Ga-DOTATOC PET and 18F-FDG PET scans using the Krenning score and PET quantification parameters for each lesion and patient. Data collection will also include clinico-biological and imaging data preceding the 68Ga-DOTATOC PET scan for each patient and lesion.