Comparison of FDG-PET/CT and Conventional CT for Response Monitoring in Metastatic Breast Cancer: A Multicenter Randomized Clinical Trial

The primary objective of the MONITOR-RCT is to demonstrate that in patients with **metastatic breast cancer** (MBC), response monitoring based on **FDG-PET/CT** is superior to response monitoring based on conventional **CT** with respect to overall survival. This objective will be assessed by applying standardized response evaluation criteria, specifically using an appropriate adaptation of the **PERCIST** criteria for FDG-PET/CT and the **RECIST1.1** criteria for CT.

Secondary objectives of the MONITOR-RCT include:

• Demonstrating superiority with respect to the quality of life.
• Evaluating time and exposure to treatment.
• Investigating the cost-effectiveness of the response monitoring methods.

The clinical trial focuses on individuals diagnosed with **metastatic breast cancer**. The study population includes both women and men aged 18 years and older. Participants are required to have a diagnosis of distant relapsed metastatic breast cancer, verified through biopsy, or de novo breast cancer with biopsy verification of the primary tumor and diagnostic imaging showing distant metastasis. The trial does not involve a vulnerable population. Participants must be eligible for first-line systemic treatment and continuous treatment monitoring through scans. Additionally, they must be able to read and understand the language requirements specific to their country of participation, such as Danish in Denmark, Italian or English in Italy, and German or English in Germany. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the efficacy of **FDG-PET/CT** compared to conventional CT in monitoring response in patients with metastatic breast cancer. This is a multicenter, randomized, double-blind, controlled trial. The primary objective is to assess whether response monitoring using FDG-PET/CT is superior to conventional CT in terms of overall survival. The trial will employ standardized response evaluation criteria, specifically adapting the PERCIST criteria for FDG-PET/CT and the RECIST1.1 criteria for CT. The trial is expected to commence recruitment on October 1, 2024, and conclude by December 31, 2029.

Participants will be involved in the study for a maximum treatment period of 54 weeks. The study will include an initial screening visit to confirm eligibility, which requires participants to be adults aged 18 years or older with a diagnosis of distant relapsed or de novo metastatic breast cancer, verified by biopsy. Participants must be eligible for first-line systemic treatment and continuous monitoring by scans. Informed consent is mandatory, and participants must be able to read and understand the language requirements specific to their country of participation.

Following the screening, participants will undergo regular follow-up visits to monitor treatment response and overall health. These visits will include imaging assessments using either FDG-PET/CT or conventional CT, depending on the randomization group. The primary endpoint of the study is overall survival, with secondary endpoints including quality of life, time and exposure to oncologic treatment, and cost-effectiveness. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination.

Early termination from the study may occur if participants experience adverse effects that contraindicate continued participation, withdraw consent, or if the investigator deems it necessary for the participant's safety. The trial is categorized as a low-intervention therapeutic use clinical trial, ensuring that the procedures align with standard clinical practices while maintaining rigorous scientific evaluation.

The clinical trial involves the use of **Fludeoxyglucose (18F)**, a radiopharmaceutical agent, as the experimental medication. This compound is utilized in the form of a solution for injection, identified by the pharmaceutical form code PHF00231MIG. The administration of Fludeoxyglucose (18F) is conducted via **intravenous administration**. The dosage is measured in megabecquerels (MBq), with a maximum daily dose and total dose amounting to 400 MBq. The treatment period is capped at 54 days. The primary role of Fludeoxyglucose (18F) in this trial is to facilitate response monitoring in patients with metastatic breast cancer, using FDG-PET/CT imaging techniques.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the application of Fludeoxyglucose (18F) for the purpose of evaluating its efficacy in response monitoring. Participant compliance with the dosing schedule is critical and will be monitored throughout the trial to ensure adherence to the protocol. The trial aims to assess the superiority of FDG-PET/CT over conventional CT in terms of overall survival, applying standardized response evaluation criteria adapted from PERCIST for FDG-PET/CT and RECIST1.1 for CT.

Efficacy in the MONITOR-RCT clinical trial will be assessed by comparing response monitoring methods in patients with metastatic breast cancer (MBC). The primary endpoint for evaluating efficacy is **overall survival**. This will be determined by applying standardized response evaluation criteria, specifically an adaptation of the PERCIST criteria for FDG-PET/CT and the RECIST1.1 criteria for conventional CT. These criteria will be used to assess the superiority of FDG-PET/CT over conventional CT in monitoring patient response.

Secondary endpoints include assessments of quality of life, time and exposure to oncologic treatment, and cost-effectiveness. These parameters will provide additional insights into the benefits of FDG-PET/CT in the management of MBC. The trial will employ validated scales and methodologies to ensure accurate and reliable data collection and analysis. The schedule for measuring these efficacy parameters will be aligned with the trial's protocol, ensuring systematic and consistent data collection throughout the study duration.