"APalutamide and stEReotactic body radiation therapy for low burden metastatic hormone senSItive prostate cancer, a rANdomized trial -PERSIAN".

The primary objective of this study is to evaluate the **rate of complete biochemical response** at 6 months from treatment initiation in patients with oligometastatic hormone-sensitive prostate cancer. This is assessed by measuring prostate-specific antigen (PSA) levels, aiming for a target of less than 0.2 ng/ml. The study compares two groups: one receiving standard systemic treatment with androgen deprivation therapy and Apalutamide (Arm A: Control), and the other receiving the same systemic treatment plus stereotactic body radiotherapy on all metastatic sites (Arm B: Treatment). This objective is clinically relevant as achieving a complete biochemical response is indicative of effective disease control and may correlate with improved patient outcomes.

Secondary objectives include:

• Time to PSA progression according to Prostate Cancer Working Group (PCWG) criteria
• Radiologic progression-free survival (rPFS) according to PCWG criteria
• Frequency of treatment-emergent adverse events (AEs)
• Overall survival
• Cancer-specific survival
• Quality of life measured with EORTC QLQ-C30 and EORTC QLQ-PR25

The clinical trial focuses on **prostate cancer** and involves a study population exclusively composed of male participants, as female subjects are not included. The age range of participants spans from 18 years and older, targeting adult patients. The trial does not involve a vulnerable population. Participants are required to have oligometastatic hormone-sensitive prostate cancer, characterized by the presence of five or fewer non-visceral metastatic lesions. All lesions must be suitable for stereotactic body radiotherapy (SBRT) as determined by the treating radiation oncologist. The trial includes patients who have experienced metastatic recurrence following previous radical prostatectomy or definitive radiotherapy, provided a radical approach on the prostate is administered. Androgen deprivation therapy (ADT) must have commenced within six months prior to enrollment, and participants should be eligible for Apalutamide treatment. 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 **apalutamide** in combination with stereotactic body radiotherapy (SBRT) for patients with oligometastatic hormone-sensitive **prostate cancer**. This is a randomized, controlled, and double-blind trial, categorized as Phase 4, with an estimated duration from February 2023 to February 2026. The primary objective is to assess the rate of complete biochemical response, defined as a prostate-specific antigen (PSA) level of less than 0.2 ng/ml, at six months post-treatment initiation. Participants will be randomly assigned to one of two arms: Arm A, receiving standard systemic treatment with androgen deprivation therapy (ADT) and apalutamide, or Arm B, receiving the same systemic treatment plus SBRT on all metastatic sites.

Study visits are structured to ensure comprehensive monitoring and data collection. The inclusion visit, or screening, will confirm eligibility based on criteria such as age (≥18 years), diagnosis of oligometastatic hormone-sensitive prostate cancer with ≤5 non-visceral metastatic lesions, and recent initiation of ADT (≤6 months prior to enrollment). Follow-up visits will occur at regular intervals to monitor treatment response, adverse events, and overall health status, using standardized tools like the EORTC QLQ-C30 and QLQ-PR25 questionnaires. The end-of-study visit will evaluate the primary and secondary endpoints, including freedom from biochemical and radiological progression, overall survival, and cancer-specific survival.

Participant involvement is expected to last up to 24 months, aligning with the maximum treatment period for apalutamide. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or any clinical judgment indicating that continued participation is not in the participant's best interest. The trial's design ensures rigorous assessment of the therapeutic benefits and safety profile of the treatment regimen, contributing valuable insights into the management of prostate cancer.

The clinical trial involves the administration of **Apalutamide**, an experimental medication, in the form of a **film-coated tablet**. The active substance, **Apalutamide**, is of chemical origin and is administered orally. The dosage is set at a maximum of 240 mg per day, with the treatment period extending up to 24 months. Participants are required to adhere to the prescribed dosing schedule to ensure consistent therapeutic levels of the medication. Compliance with the dosing regimen will be monitored throughout the study to ensure accurate assessment of the treatment's efficacy and safety.

In addition to the experimental treatment, participants in the control arm (Arm A) will receive standard systemic treatment, which includes **androgen deprivation therapy** combined with Apalutamide. This serves as the comparator treatment to evaluate the added benefit of stereotactic body radiotherapy in the treatment arm (Arm B). The study aims to assess the rate of complete biochemical response at 6 months, defined as a prostate-specific antigen (PSA) level of less than 0.2 ng/ml, in patients with oligometastatic hormone-sensitive prostate cancer. The trial will compare outcomes between patients receiving the standard treatment alone and those receiving the additional radiotherapy.

Efficacy in this clinical trial will be assessed by evaluating the **rate of complete biochemical response** at 6 months from the start of treatment, defined as a prostate-specific antigen (PSA) level of less than 0.2 ng/ml. This primary endpoint will be used to compare the benefit of adding stereotactic body radiotherapy to standard systemic treatment, which includes androgen deprivation therapy and Apalutamide, in patients with oligometastatic hormone-sensitive prostate cancer. The trial will involve two arms: Arm A (Control) with standard systemic treatment alone, and Arm B (Treatment) with the addition of stereotactic body radiotherapy.

Secondary endpoints will include freedom from biochemical progression and radiological progression, both assessed according to the Prostate Cancer Working Group Criteria. Additionally, the rate of adverse events will be measured using the Common Terminology Criteria for Adverse Events. Overall survival, cancer-specific survival, and health-related quality of life will also be evaluated, with the latter being measured using the EORTC QLQ-C30 and QLQ-PR25 questionnaires. These assessments will provide a comprehensive evaluation of the treatment's efficacy and its impact on patients' quality of life.