Veterans affairs seamless phase II/III randomized trial of standard systemic therapy with or without PET-directed local therapy for oligorecurrent prostate cancer (VA STARPORT).

TPS5112 Background: Two diverging paradigms have been studied in recent years to improve the survival of men with recurrent metastatic prostate cancer (PCa). First, multiple recent phase II randomized trials have demonstrated improved long-term progression-free survival (PFS) with metastasis-directed therapy (MDT) in men with oligorecurrent PCa in the absence of systemic therapy. Yet, most patients receiving MDT for oligorecurrent PCa develop progression in new areas, arguing that systemic therapy is needed to treat occult metastases. The second approach that has recently been studied is whether escalating systemic therapy by adding novel androgen receptor axis targeted agents or chemotherapy improves outcomes in men with metastatic PCa. Multiple phase III randomized trials demonstrate that enhancing hormonal therapy with these therapeutic agents improves progression-free survival (PFS) and overall survival. Therefore, these agents have been integrated into today’s standard systemic therapy (SST) for metastatic recurrence, and SST is the current NCCN guidelines standard of care for recurrent metastatic PCa. The primary goal of our study is to determine if adding PET-directed local therapy (PDLT) to SST improves disease control compared to SST alone in Veterans with oligorecurrent PCa. Methods: VA STARPORT is a phase II/III randomized trial open at 16 VA medical centers comparing SST with or without PDLT in Veterans with oligorecurrent PCa. Key eligibility criteria include prior localized PCa with biochemical recurrence after initial curative-intent local therapy and workup including any FDA-approved PCa PET/CT that reveals oligorecurrence in 1-5 metastatic lesions. The primary endpoint is castration-resistant prostate cancer-free survival (CRPC-free survival). Secondary endpoints include radiographic PFS, clinical PFS, freedom from index lesion progression, toxicity, quality of life, and prostate cancer-specific and overall survival. SST is delivered with an intent for indefinite SST using any NCCN guideline-concordant regimen in both arms. PDLT (Arm 2) consists of surgery or radiation to metastases and any present prostate/prostate bed local recurrence. Metastasis-directed radiation can consist of stereotactic body radiotherapy or elective nodal radiotherapy per clinician discretion from dose/fractionation options defined in the protocol. All participants undergo somatic tumor sequencing using the VA National Precision Oncology Program. Germline sequencing and tumor banking in a separate biorepository study is recommended. Assuming a hazard ratio of 0.60 for SST + PDLT vs SST, two-sided alpha = 0.05 and 90% power, a total of 464 participants will be randomized to generate 166 primary events (CRPC-free survival) by the end of the 48-month active study phase. The study began enrollment in August 2021. Clinical trial information: NCT04787744.