Comparison of Conventional Salvage Radiotherapy and Individualized PSMA-PET/CT Targeted Treatment in Biochemical Recurrence Post-Prostatectomy Using 18F-PSMA-1007 and Gozetotide

The primary objective of this study is to compare the efficacy of individualized **PSMA PET/CT** targeted treatment with conventional "salvage" radiotherapy in patients experiencing biochemical recurrence after prostate cancer surgery. The main focus is on **PSA progression-free survival**, which is clinically significant as it may indicate the effectiveness of the treatment in delaying disease progression and improving patient outcomes.

Secondary objectives include comparing the following outcomes between the two treatment approaches:

• Quality of life outcomes
• Time to secondary treatment
• Time to metastasis
• Overall and cancer-specific survival
• Health economics

The clinical trial focuses on **biochemical recurrence after prostate cancer surgery**. The study population consists exclusively of male participants, as indicated by the trial's gender-specific criteria. The age range of participants spans from 18 to 64 years, encompassing both young adults and middle-aged individuals. The trial does not include a vulnerable population. Participants were selected based on their previous treatment for prostate cancer with radical prostatectomy and the presence of a biochemical recurrence, defined by a PSA level greater than 0.2 ng/mL but less than 2.0 ng/mL, with an increasing trend confirmed by two measurements. Additionally, a multidisciplinary conference decision to offer salvage radiotherapy was required, along with signed informed consent. 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 efficacy of individualized **PSMA PET/CT** targeted treatment compared to conventional "salvage" radiotherapy in patients experiencing biochemical recurrence after prostate cancer surgery. This study employs a randomized, controlled, and double-blind methodology to ensure the reliability and validity of the results. The trial is expected to span a duration of approximately ten years, with an estimated recruitment start date in November 2018 and an anticipated end date in November 2028.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a history of radical prostatectomy and a specific range of PSA levels. Following randomization, participants will receive either the conventional or individualized treatment. Follow-up visits will be scheduled at regular intervals to monitor PSA progression-free survival, the primary endpoint, and secondary endpoints such as time to metastasis, prostate cancer-specific survival, and overall survival. Quality of life assessments will be conducted using the PSMA-PROM questionnaire at baseline and at 6, 12, 36, and 60 months post-treatment.

The expected length of participant involvement in the trial is contingent upon the treatment arm and individual response, with the maximum treatment period set at one year. Conditions that may lead to early termination from the study include adverse reactions to the treatment, withdrawal of consent, or any significant protocol deviations. The trial aims to provide comprehensive data on the comparative effectiveness of the two treatment modalities, contributing valuable insights into the management of biochemical recurrence in prostate cancer patients.

The clinical trial involves the administration of **18F-PSMA-1007**, a radiopharmaceutical used for imaging in patients with biochemical recurrence after prostate cancer surgery. This experimental medication is provided in the form of a **solution for injection**. The active substance is chemically synthesized and identified as (3S,10S,14S)-1-[4-[[(2S)-4-carboxy-2-[(2S)-4-carboxy-2-(6-[18F] fluoropyridin-3-amido)butanamido]butanamido]methyl]phenyl]-3-[(naphthalen-2-yl)methyl]-1,4,12-trioxo-2,5,11,13-tetraazahexadecane-10,14,16-tricarboxylic acid. The solution is administered via **intravenous use** with a maximum daily dose of 250 Bq (becquerel) and a total dose not exceeding 250 Bq over a treatment period of one day. Participant compliance with the dosing schedule is monitored throughout the trial.

Additionally, the trial utilizes **Locametz 25 micrograms kit for radiopharmaceutical preparation**, which contains the active substance **gozetotide**. This product is also administered as a **solution for injection** and is used in the preparation of radiopharmaceuticals. The administration route is **intravenous**, with a maximum daily dose of 150 MBq (megabecquerel) and a total dose not exceeding 300 MBq over a one-day treatment period. The preparation and administration of this product are conducted under controlled conditions to ensure participant safety and adherence to the protocol.

Both treatments are chemical in origin and are not formulated for pediatric use. The trial does not include any orphan drug designations. The study aims to compare the efficacy of these individualized PSMA PET/CT targeted treatments with conventional "salvage" radiotherapy, focusing on PSA progression-free survival as the main objective. No additional non-experimental treatments, such as standard-of-care therapy or placebo, are specified in the trial protocol.

The efficacy of the clinical trial will be assessed by comparing the outcomes of individualized PSMA PET/CT targeted treatment with conventional "salvage" radiotherapy in patients experiencing biochemical recurrence after prostate cancer surgery. The primary endpoint for evaluating efficacy is **PSA progression-free survival (PFS)**. This is defined as documented biological progression, which includes no response to salvage radiotherapy (SRT) if the PSA value three months post-SRT is ≥ 0.1 ng/mL higher than the PSA value just before radiotherapy. Additionally, progression after an initial response to SRT is indicated by two rising PSA values ≥ 0.1 ng/mL after radiotherapy completion, with the last value being ≥ 0.2 ng/mL.

Secondary endpoints include time to metastasis, prostate cancer-specific survival, overall survival, and time to secondary treatment, which is the duration from randomization to the initiation of secondary treatment, typically hormonal therapy. Quality of life will also be assessed using the PSMA-PROM, a study-modified quality of life questionnaire developed by the National PCa Register. This questionnaire will be completed by all patients at baseline and at 6, 12, 36, and 60 months following the completion of treatment. These efficacy parameters will be measured and collected at specified timepoints to ensure comprehensive analysis and comparison of the treatment modalities.