Assessment of 68Ga-NOTA-Anti-HER2 VHH1 Uptake in Brain Metastases of HER2-Positive and HER2-Negative Cancer Patients

The primary objective of this study is to compare the uptake of **68GaNOTA-Anti-HER2 VHH1** in brain metastasis lesions from HER2-positive and HER2-negative cancer patients. This evaluation is clinically relevant as it may provide insights into the differential uptake patterns of the radiotracer in metastatic brain lesions, potentially influencing diagnostic and therapeutic strategies for patients with HER2-positive and HER2-negative brain metastases. No secondary objectives are specified for this study.

The clinical trial involves **cancer patients with brain metastasis**, specifically focusing on the uptake of 68GaNOTA-Anti-HER2 VHH1 in brain metastasis lesions from HER2-positive and HER2-negative patients. The study population includes both male and female participants aged 18 years and older. Participants are required to have at least one brain lesion with a minimum diameter of 8 mm, as determined by CT or MRI. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include patients who have given informed consent and those with potentially HER2-positive cancer, with either prior HER2 staining or sufficient tissue available for HER2 staining for study purposes. No specific lifestyle considerations such as diet or physical activity are mentioned. The trial population was selected based on these criteria, ensuring a focus on individuals with the relevant medical condition and characteristics.

The clinical trial is designed to evaluate the uptake of **68Ga-NOTA-anti-HER2 VHH1** in brain metastasis of cancer patients. This is a Phase IV, randomized, double-blind, controlled study aimed at comparing the uptake in brain metastasis lesions from HER2-positive and HER2-negative patients. The trial is expected to run from October 16, 2017, to December 31, 2026. Participants will be involved in the study for a maximum treatment period of three days, with a total dose not exceeding 185 MBq of the investigational product, administered via intravenous injection.

The study will commence with an inclusion visit, where potential participants will be screened based on specific criteria, including age (18 years or older), presence of brain metastasized cancer with at least one brain lesion of at least 8 mm in diameter, and potential HER2-positive cancer status. Informed consent is required for participation. Following the inclusion visit, participants will undergo baseline imaging to assess the uptake of the investigational product. Subsequent follow-up visits will be scheduled to monitor the uptake during and after treatment, with comparisons made to baseline values. The primary endpoint involves the visual and quantitative assessment of tumor targeting potential in brain metastasis by an experienced nuclear medicine physician, who will be blinded to the HER2 status of the patients. Secondary endpoints include the evaluation of uptake changes over time and correlation with the patient's disease course.

The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted. Participants may be withdrawn from the study if they experience adverse reactions, fail to comply with study procedures, or withdraw consent. The trial's design ensures rigorous assessment of the investigational product's efficacy and safety, contributing valuable data to the understanding of its potential therapeutic benefits in cancer patients with brain metastasis.

The clinical trial involves the administration of the experimental medication **68Ga-NOTA-anti-HER2 VHH1**, which is a **solution for injection**. This investigational product is designed to evaluate its uptake in brain metastasis of cancer patients, specifically comparing uptake in HER2-positive and HER2-negative patients. The active substance, **68Ga-NOTA-anti-HER2 VHH1**, is a protein-based compound categorized under "Protein - Other." The pharmaceutical form of the medication is a solution intended for **intravenous administration**. The maximum daily dose is set at 185 MBq (megabecquerels), with the same amount being the maximum total dose allowed. The treatment period is limited to a maximum of three days.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus remains solely on the investigational product, **68Ga-NOTA-anti-HER2 VHH1**. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The investigational product is not formulated for pediatric use and is not classified as an orphan drug. The trial is conducted under the authorization of UZ Brussel, ensuring compliance with regulatory standards.

Efficacy in this clinical trial will be assessed by evaluating the uptake of **68Ga-NOTA-anti-HER2 VHH1** in brain metastasis lesions of cancer patients. The primary endpoints include the visual and quantitative assessment of tumor targeting potential in brain metastasis. An experienced nuclear medicine physician, who is unaware of the HER2-status, will visually score the tumor targeting potential as positive or negative. Additionally, the tumor targeting potential will be quantitatively assessed using Standard Uptake Values (SUV). These assessments will provide insights into the efficacy of the investigational product in targeting brain metastasis.

Secondary endpoints involve evaluating the uptake during and after treatment, comparing it to baseline values, and correlating the results with the patient's disease course. This will help in understanding the changes in uptake over time and its potential implications on disease progression. The trial is designed to compare the uptake in HER2-positive and HER2-negative patients, providing a comprehensive analysis of the investigational product's efficacy in different patient subgroups.