3269 - STARLiT: A Single Arm Phase I/II Trial of STereotActic Body Radiotherapy and <sup>177</sup>Lutetium PSMA in Locally Advanced Prostate Cancer
Presenter(s)
Q. Li1, R. Kashani2, Y. Dewaraja3, W. C. Jackson4, R. T. Dess4, D. J. Gorovets5, H. Nagar6, Q. Li7, P. Mendiratta8, J. Brown8, S. Rao8, I. Y. Sheng8, Y. Sun9, J. Garcia8, D. E. Spratt1, and A. Y. Jia1; 1Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, 2Case Western Reserve University, Cleveland, OH, 3Department of Radiology, University of Michigan, Ann Arbor, MI, 4Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 5Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 6Memorial Sloan Kettering Cancer Center, New York, NY, 7Department of Radiology, University Hospitals, Case Western Reserve University, Cleveland, OH, 8Department of Hematology and Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, 9Case Western Reserve University School of Medicine, Cleveland, OH
Purpose/Objective(s): Prostate cancer (PCa) is the most common cancer type in men and is the second leading cause of cancer death in men. High risk prostate cancer (AJCC Stage IIIB and IIIC) and clinically node-positive disease (AJCC Stage IVA) account for 30% of de novo PCa diagnoses and the majority of deaths are from patients who are diagnosed with non-metastatic disease. The most common treatment for this patient subset is radiation therapy (RT) plus long-term androgen deprivation therapy (ADT) for 18-36 months with consideration for the addition of abiraterone acetate. However, high toxicity rates of ADT and substantial impact on patient-reported quality of life have resulted in decreased compliance to long-term ADT. Lutetium-177[177Lu]-PSMA-617 is FDA-approved in the treatment of castrate resistant PCa, with favorable toxicity profile. STARLiT aims to evaluate the safety of combining 177Lu-PSMA-617 with SBRT to the prostate and to determine whether 177Lu-PSMA-617 can replace ADT to improve disease control by use of cytotoxic agents, avoid side effects and improve patient compliance to receive systemic therapy.
Materials/Methods: STARLiT is a phase I/II, single-arm, open-label trial enrolling 45 patients with locally advanced prostate cancer. Locally advanced disease is defined as PSMA PET/CT-avid disease (SUVmax =10) with pelvic or regional nodes (up to aortic bifurcation), or in the absence of nodal disease, patients must have =2 of the following: cT3 disease (by exam or imaging), Grade Group =4, or PSA = 40. Patients receive 1 cycle of 7.4GBq 177Lu-PSMA-617, followed by 5 fraction SBRT to the prostate and elective nodal fields, and potentially two more cycles of 177Lu-PSMA-at 6-week intervals in between.
Results: The primary objectives are Phase I: to determine the maximally tolerated dose (MTD, defined as maximum number of 7.4 GBq cycles) of 177Lu-PSMA-617 and Phase II: to assess 3-year ADT-free survival. Secondary objectives include 24-month PSA progression-free survival, overall survival, prostate cancer-specific survival, distant metastasis, time to any salvage therapy, and quality of life (EPIC-26, XeQoLS, FACT-RNT). Key correlative studies include tumor and normal organ dosimetry. The primary safety outcome is to determine the incidence of dose-limiting toxicities (DLT). The TITE-CRM algorithm will be utilized to guide dose escalation, with the MTD defined as the dose that is associated with a 20% DLT. Assuming the DLT rate is between 15-20%, approximately 24 patients are expected to be treated at the MTD and will be included in the Phase II analysis.
Conclusion: The trial was activated in February 2025 and aims to complete accrual within 18 months with a 5-year follow-up.