Treatment of Patients With Progressive mCRPC With 177Lu-PSMA-617

This clinical study investigates the safety and effectiveness of the FDA-approved drug Pluvicto (Lu-177-PSMA617). It focuses on a unique group of patients with metastatic castration-resistant prostate cancer (mCRPC) who present with a "super scan" on bone scintigraphy-a pattern indicating widespread cancer in the bones. These patients were excluded from prior trials like the VISION study, leaving a critical gap in clinical understanding. The trial aims to identify the optimal safe dose of Pluvicto using a modified 3+3 dose-escalation method, beginning at a low dose that increases, and eventually reaching up to 200 mCi. Participants will receive a total of six doses, spaced every 6 ± 1 weeks. Primary objectives include determining the maximum tolerated dose and monitoring safety using CTCAE version 5.0 criteria. Efficacy will be evaluated through PSA level reductions based on PCWG3 guidelines. Secondary endpoints include quality of life, radiologic response (RECIST v1.1), and overall survival. Exploratory endpoints involve PSMA PET/CT imaging to measure treatment response through SUVmean and lesion changes. The study includes up to 30 participants and will include expanded enrollment once the optimal dose is determined. Routine lab tests (CBC, CMP, PSA, testosterone) and patient-reported side effects will be monitored throughout the study. Long-term follow-up for survival and safety will continue every six months for up to five years. Imaging (CT/MRI, bone scans, and optional PET/CT) will be performed at baseline, mid-treatment, end of treatment, and every three months post-treatment. A complete or partial response, stable disease, or progression will be defined using both RECIST and PCWG3 guidelines. Monthly PSA checks will continue for up to 24 months or until disease progression. PLUVICTO is administered via IV infusion over 2-5 minutes during each session. Participants may discontinue due to progression, intolerable side effects, non-compliance, or other clinical decisions. This study is essential in determining how to safely extend Pluvicto therapy to a previously unstudied and high-risk patient group. Its results may expand access to this radioligand therapy and guide future treatment decisions in prostate cancer care.