Evaluation of Fractionated Stereotactic Radiotherapy Combined with Abiraterone Acetate and Enzalutamide in Oligometastatic Castration-Resistant Prostate Cancer

The primary objective of this study is to determine the **progression-free survival** (PRFS) in patients with oligometastatic castration-resistant prostate cancer (mCRPC) treated with a combination of second-generation antiandrogen therapy and fractionated stereotactic body radiotherapy (SBRT). PRFS is measured from the initiation of the antiandrogen treatment to the time of radiological progression, as assessed by choline PET/CT or 68Ga-PSMA PET/CT. This objective is clinically relevant as it aims to evaluate the efficacy of the treatment combination in delaying disease progression, which is crucial for improving patient outcomes in mCRPC.

Secondary objectives include:

• Evaluating overall survival, defined as the time from the initiation of second-generation antiandrogen therapy to death, in patients treated with the combination therapy.
• Assessing the quality of life of these patients using the European Organization for Research and Treatment of Cancer (EORTC) quality of life scale, EORTC QLQ-C30, which is validated for oncology patients.
• Monitoring acute and chronic toxicity according to the "Common Terminology Criteria for Adverse Events" (CTCAEv5.0) scale.

The clinical trial involves **oligometastatic patients with castration-resistant prostate cancer**. The study population is exclusively male, with an age range that includes adults and the elderly. Participants are required to have a histologically confirmed diagnosis of prostate adenocarcinoma, with biochemistry progression confirmed according to Phoenix criteria, and testosterone levels in castration range. Radiological confirmation of up to five node or bone metastases, non-visceral, is necessary, with eligibility for SBRT treatment. Candidates must be suitable for treatment with abiraterone or enzalutamide, as determined by their physician prior to study inclusion. Participants must have a life expectancy greater than three months and provide written informed consent. The sponsor has not provided information regarding the total number of participants. The trial does not include female subjects or vulnerable populations. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **second-generation antiandrogen** therapy combined with fractionated stereotactic radiotherapy in patients with oligometastatic castration-resistant prostate cancer. This is a Phase II, prospective, multicenter study conducted in Spain. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The estimated duration of the trial is from October 2023 to July 2028, with a maximum treatment period of 36 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as histologically confirmed prostate adenocarcinoma and radiological confirmation of metastasis. Following the screening, eligible participants will be randomized to receive either **abiraterone acetate** or **enzalutamide**, both administered orally in the form of film-coated tablets. The primary endpoint is the progression-free survival measured from the initiation of the antiandrogen therapy to radiological progression, assessed by choline PET/CT or 68Ga-PSMA PET/CT.

Throughout the trial, participants will attend regular follow-up visits to monitor treatment efficacy and safety, including assessments of overall survival, quality of life, and toxicity using the EORTC QLQ-C30 and CTCAEv5.0 scales. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination. Participants may be withdrawn from the study if they experience unacceptable toxicity, disease progression, or withdraw consent. The expected length of participant involvement is up to 36 months, contingent upon individual response and tolerance to the treatment regimen.

The clinical trial involves the administration of two **experimental medications** for patients with castration-resistant prostate cancer. The first medication is **Abiraterone Normon**, which is provided in the form of 500 mg **film-coated tablets**. The active substance in this medication is **abiraterone acetate**, a chemical compound. The tablets are administered orally, with a maximum daily dose of 1000 mg. The treatment period for this medication is up to 36 months. The medication is manufactured by Laboratórios Normon, S.A., and is not a pediatric formulation. Compliance with the dosing schedule will be monitored throughout the trial.

The second medication used in the trial is **Xtandi**, which consists of 80 mg **film-coated tablets**. The active substance in Xtandi is **enzalutamide**, also a chemical compound. This medication is also administered orally, with a maximum daily dose of 160 mg. Similar to Abiraterone Normon, the treatment period for Xtandi is up to 36 months. Xtandi is produced by Astellas Pharma Europe B.V. and is not intended for pediatric use. Participant adherence to the dosing regimen will be closely monitored to ensure compliance.

Both medications are part of a combination therapy with fractionated stereotactic radiotherapy, aiming to evaluate the progression-free survival in patients with oligometastatic castration-resistant prostate cancer. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in this study. The trial is designed to assess the efficacy of these second-generation antiandrogens in conjunction with radiotherapy.

Efficacy in this clinical trial will be assessed through a combination of primary and secondary endpoints. The primary endpoint is the measurement of **radiological progression** in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with a combination of second-generation antiandrogen therapy and stereotactic body radiotherapy (SBRT). This progression will be evaluated using choline PET/CT or 68Ga-PSMA PET/CT imaging techniques.

Secondary endpoints include overall survival, defined as the time from the initiation of second-generation antiandrogen therapy to death. Additionally, the quality of life of patients will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 scale, which is validated for oncology patients. The trial will also monitor acute and chronic toxicity using the Common Terminology Criteria for Adverse Events (CTCAEv5.0) scale.