A pragmatic phase 2 trial of locally ablative therapy in oligo-progressive genitourinary (GU) tumors: LAYOVER

Abstract

TPS291 Background: Oligoprogressive disease (OPD) may represent an opportunity for locally ablative therapies to provide disease control in patients otherwise responding to systemic therapy. In GU malignancies, retrospective data suggest that ablating resistant clones in OPD sites with metastasis-directed therapies (MDT) such as stereotactic ablative radiotherapy (SABR) while continuing systemic therapy can delay further progression. Limited prospective trials have assessed MDT in oligoprogressive GU malignancies. As pragmatic trials assess the efficacy of interventions in a heterogenous, representative patient population under otherwise routine clinical care, this streamlined design is well-suited to evaluate the role of MDT in patients with oligoprogressive GU cancers. Methods: This pragmatic Phase 2 study enrolls patients with histologically or biochemically confirmed GU cancers into three cohorts: prostate cancer, urothelial carcinoma, and renal cell carcinoma. Eligible patients are ≥ 18 years old, currently receiving systemic therapy and have demonstrated ≥ 3 months of clinical benefit on current treatment, defined as treating provider assessment of stable disease and not requiring change in systemic therapy. Patients must have OPD, defined as radiographic progression in 5 or fewer metastatic lesions. Patients cannot have progressing intracranial lesions or a history of treatment-related toxicities that preclude the use of locally ablative therapies. Eligible participants are assigned to receive SABR or image-guided percutaneous ablation per the discretion of treating physicians, while continuing systemic therapy. Patients will be followed for up to 5 years following ablative local therapy. The primary endpoint of the trial is 3-month disease control rate (DCR), defined as continuation in systemic therapy without changes or permanent discontinuation for 3 months following first day of ablative local therapy. Secondary endpoints include evaluation of high-grade toxicity, overall survival, and time to systemic treatment failure. A lead-in stage of 15 participants are enrolled for each cohort, and based on Simon’s minimax two-stage design, if ≥ 2 patients are responding at 3-months, then additional expansions are planned to reach a total of 50 participants. The prostate cancer cohort has completed accrual of the lead-in phase and met criteria for further expansion, while other lead-in cohorts continue to accrue. Clinical trial information: NCT06101290 .