Comparison of 18F-Fluciclovine and 18F-Fluoroethyltyrosine PET in Newly Diagnosed and Recurrent Cerebral Gliomas and Brain Metastases

The primary objective of this study is the **assessment** of agreement on tumour size and tracer distribution in **FET PET** and **FACBC PET** in patients with newly diagnosed cerebral gliomas, recurrent cerebral gliomas, and brain metastases. This is clinically relevant as it aims to enhance the accuracy of imaging techniques in evaluating tumour characteristics, which is crucial for effective treatment planning and monitoring of these conditions.

Secondary objectives include: - Determining the correlation of the tumour-to-brain ratios in **FET** and **FACBC PET**. - Evaluating the difference in **FET** to **FACBC** uptake concerning Time-to-peak (TTP) or slope of the time-activity curve (TAC) in high-grade and low-grade gliomas. - Assessing the accuracy of **FET** to **FACBC PET** in differentiating tumour progression (TP) and treatment-related changes (TRC) in recurrent gliomas and brain metastases. - Investigating the difference in **FET** to **FACBC PET** with respect to TTP and slope of the TAC of **FET** and **FACBC** uptake in TP and TRC in recurrent gliomas and brain metastases.

The clinical trial involves **patients** with newly diagnosed cerebral gliomas, recurrent cerebral gliomas, and brain metastases. The sponsor has not provided information regarding the total number of participants. The study population includes both male and female subjects aged 18 years and older. Participants are required to be mentally and physically capable of understanding the study's significance and scope, as well as complying with study procedures. They must have decision-making capacity, including the ability to give informed consent. The trial does not include a vulnerable population. Participants are referred to the Nuclear Medicine Clinic of the University Hospital Aachen for FET PET of the brain based on a physician's prescription. The study does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include having a suspected glioma prior to biopsy or surgery or suspected tumor recurrence after previous treatment for cerebral glioma or brain metastasis.

The clinical trial is designed as an open-label, single-center, single-arm, prospective basket trial. It aims to compare **18F-Fluciclovine PET** with **18F-Fluoroethyltyrosine PET** in patients with newly diagnosed cerebral gliomas, recurrent cerebral gliomas, and brain metastases. The primary objective is to assess the agreement on tumor size and tracer distribution between the two imaging modalities. The trial is categorized as a Phase 4 study and is considered low intervention. The trial is expected to commence recruitment on March 31, 2024, and conclude by March 31, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), mental and physical capacity to understand the study, and a signed informed consent form. The inclusion criteria also require that participants are referred to the Nuclear Medicine Clinic for a FET PET scan of the brain. The study will involve intravenous injection of the investigational products, which include Axumin solutions and FET, with a maximum daily dose of 185 MBq and a total dose not exceeding 222 MBq. The maximum treatment period is limited to one day.

Follow-up visits will be scheduled to monitor the participants and collect data on the primary and secondary endpoints. The primary endpoint focuses on the agreement of tumor size and tracer distribution diagnosis between FET PET and FACBC PET, assessed by consensus voting among three examiners. Secondary endpoints include the correlation of tumor-to-brain ratios and the accuracy of the imaging modalities in differentiating tumor progression from treatment-related changes.

The expected duration of participant involvement is limited to the study visits required for data collection, with no long-term follow-up. Conditions that may lead to early termination from the study include withdrawal of consent or any adverse events that compromise participant safety. The trial's design ensures that all procedures adhere to ethical standards and regulatory requirements, with a focus on maintaining the integrity and scientific validity of the study outcomes.

The clinical trial involves the administration of **Axumin 3,200 MBq/mL solution for injection**, which contains the active substance **fluciclovine (18F)**. This pharmaceutical form is a solution for injection, administered via **intravenous injection**. The maximum daily dose is 185 MBq, with a total maximum dose of 222 MBq. The treatment period is limited to one day. Axumin is produced by Blue Earth Diagnostics Ireland Ltd and is designated as an orphan drug with the authorization number EU/1/17/1186/002. The solution is not formulated for pediatric use.

Another experimental medication used in the trial is **Axumin 1,600 MBq/mL solution for injection**, also containing **fluciclovine (18F)**. Similar to the 3,200 MBq/mL formulation, it is administered as a solution for injection via **intravenous injection**. The dosing parameters are consistent, with a maximum daily dose of 185 MBq and a total maximum dose of 222 MBq, administered over a single day. This formulation is also produced by Blue Earth Diagnostics Ireland Ltd and holds the marketing authorization number EU/1/17/1186/001. It is not intended for pediatric use and is classified as an orphan drug.

The comparator treatment in the study is **FET**, which contains the active substance **fluoroethyltyrosine F-18**. This solution for injection is administered through **intravenous injection**. The dosing schedule allows for a maximum daily dose of 185 MBq and a total maximum dose of 222 MBq, with the treatment period restricted to one day. FET is produced by Universitaetsklinikum Aachen AöR and is not designated as an orphan drug. It is also not formulated for pediatric use.

Efficacy in this clinical trial will be assessed by evaluating the agreement on **tumour size** and **tracer distribution** between FET PET and FACBC PET in patients with cerebral gliomas and brain metastases. The primary endpoint is the consensus-based agreement of tumour size and tracer distribution diagnosis, classified into categories A or B by three examiners. Categories C and D will indicate disagreement. Secondary endpoints include the correlation of tumour-to-brain ratios in FET and FACBC PET, and the comparison of Time-to-peak (TTP) and slope of the time-activity-curve (TAC) for FET and FACBC uptake in both high-grade and low-grade gliomas. Additionally, the trial will assess the accuracy of FET and FACBC PET in differentiating tumour progression from treatment-related changes in recurrent gliomas and brain metastases, as well as the differences in TTP and TAC slope in these conditions.