Evaluation of PSMA-PET and mpMRI in high-risk prostate cancer – using histopathologic validation

The primary objective of this study is to evaluate and compare the accuracy of **PSMA-PET** and **mpMRI** in identifying and delineating the most clinically relevant intra-prostatic lesions or sub-regions in patients with high-risk **prostate cancer**. This is clinically significant as accurate identification and delineation of these lesions are crucial for effective treatment planning and management of prostate cancer.

Secondary objectives include: - Studying the prognostic potential of PSMA-PET and mpMRI using histopathology as the reference standard. - Investigating the potential for risk classification of lesions or subparts of lesions, including extracapsular extension and seminal vesicle involvement. - Exploring image processing steps that improve the correlation between histopathology, molecular characteristics, and imaging. - Investigating the potential use of machine learning to predict tumor lesion properties from mpMRI and PSMA-PET. - Exploring the possibility of defining these types of lesions in future radiotherapy patients, where they can be subject to a radiotherapy boost to maximize the probability of curing the patient. - Assessing any subject-reported adverse events to evaluate safety.

The clinical trial involves a study population exclusively composed of **male** subjects diagnosed with **prostate cancer**. The participants are adults aged 18 years and older, with no upper age limit specified. The trial does not include any vulnerable populations. The sponsor has not provided the total number of participants. The selection criteria for the trial population include individuals with histologically confirmed high-risk prostate cancer who are scheduled for radical prostatectomy. Participants must have undergone PSMA-PET/CT as part of their clinical management and meet specific clinical criteria, such as a Gleason score of 8 or higher, PSA levels between 20-49 ng/ml, or evidence of extra-prostatic growth on mpMRI. All participants are required to have given written consent to participate in the trial. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate and compare the accuracy of **PSMA-PET** and mpMRI in identifying and delineating clinically relevant intra-prostatic lesions in patients with high-risk **prostate cancer**. This study is structured as a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thus minimizing bias. The trial is expected to commence on February 1, 2024, and conclude by December 31, 2031, with the primary endpoint being the spatial definition of aggressive prostate cancer lesions using PSMA-PET and/or mpMRI compared to histopathology.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically confirmed high-risk prostate cancer, prior PSMA-PET/CT, and a minimum of four weeks since the last prostate biopsy. Subsequent visits will include follow-up assessments to monitor the accuracy of imaging techniques and any adverse events. The end-of-study visit will evaluate the primary and secondary endpoints, including biochemical disease-free survival and surgical margins.

The expected length of participant involvement is approximately one year, with conditions for early termination including withdrawal of consent or the occurrence of significant adverse events. The trial will utilize several investigational products, including **18F-PSMA-1007**, administered via intravenous injection, and auxiliary products such as **Buscopan**, **Dotarem**, and **Glucagon**, each with specific administration routes and dosage limits. The study aims to provide valuable insights into the effectiveness of imaging modalities in the management of high-risk prostate cancer, contributing to improved diagnostic and treatment strategies.

The clinical trial involves the administration of **18F-PSMA-1007**, a radiopharmaceutical used for imaging in high-risk prostate cancer. This experimental medication is provided as a **solution for injection** and is administered via **intravenous injection**. The dosage is calculated based on the patient's weight, with a maximum daily and total dose of 3.5 MBq/kg. The treatment period is limited to a single day. The active substance, 18F-PSMA-1007, is of chemical origin and is not formulated for pediatric use.

**Buscopan 20 mg/ml**, containing the active substance **hyoscine butylbromide**, is used as an auxiliary treatment in the study. It is also provided as a **solution for injection** and is administered **subcutaneously**. The maximum daily and total dose is 100 mg, with the treatment period restricted to one day. Hyoscine butylbromide is a chemical compound and is not intended for pediatric formulations.

**Dotarem 279.3 mg/ml**, with the active ingredient **gadoteric acid**, serves as another auxiliary treatment. This **solution for injection** is administered **intravenously**. The maximum daily and total dose is 20 ml, and the treatment is limited to a single day. Gadoteric acid is a chemical substance and is not designed for pediatric use.

**Glucagon Novo Nordisk 1 mg**, containing the active substance **glucagon**, is also utilized as an auxiliary treatment. It is provided as a **solution for injection** and administered via **intramuscular injection**. The maximum daily and total dose is 2 mg, with the treatment period confined to one day. Glucagon is a protein-based substance and is not formulated for pediatric use.

Efficacy in this clinical trial will be assessed through a combination of primary and secondary endpoints. The primary endpoint focuses on the identification and delineation of spatially defined aggressive **prostate cancer** lesions or subparts of lesions using PSMA-PET and/or mpMRI, with histopathology serving as the reference standard. This approach aims to evaluate the accuracy of these imaging modalities in detecting clinically relevant intra-prostatic lesions.

Secondary endpoints include biochemical disease-free survival, time to relapse, overall survival, and surgical margins. Additionally, the trial will assess radiological extracapsular extension and seminal vesicle involvement, comparing these findings to histopathological evaluations. An exploratory endpoint will further investigate the spatially defined most aggressive prostate cancer lesions or subparts of lesions. Safety will be monitored through subject-reported adverse events up to one week post-treatment.