Consolidative use of radiotherapy to block oligoprogression in patients with metastatic melanoma on Systemic Therapy (CURB-Melanoma) - a single arm, phase 2 clinical trial.

Purpose/objective: Patients with metastatic melanoma on active systemic therapy can develop isolated disease progression while the majority of disease remains controlled (oligoprogression). This phase 2 trial investigates whether stereotactic body radiation therapy (SBRT) or hypofractionated radiation to oligoprogressive sites can improve progression-free survival (PFS) in metastatic melanoma patients receiving first-line systemic therapy. Materials/methods: This is an open-label, single-arm phase 2 trial. Eligible patients have metastatic melanoma with ≤10 extracranial oligoprogressive sites while on first-line systemic therapy. Oligoprogression is defined using modified RECIST 1.1 or PERCIST criteria. All oligoprogressive sites will receive SBRT per institutional guidelines, typically delivered over 3 fractions. Patients will stay on current systemic therapy. The primary endpoint is PFS defined as the time from enrollment to the date of further disease progression. Secondary endpoints include overall survival, time on current systemic therapy, out-of-field response, tolerance of SBRT, and quality of life (QOL). In addition, serial blood samples are collected for exploratory analyses of circulating tumor DNA (ctDNA), mutant allele fraction, and immune profiling (including CD8+ T-cell subsets). The trial aims to enroll 52 patients over 12 months with additional 24 months of follow-up. Discussion: This trial will evaluate the impact of SBRT on further disease progression, treatment tolerance, and blood-based immune and molecular correlatives in patients with oligoprogressive metastatic melanoma. Findings may help define the standard of care for managing oligoprogression during first-line systemic therapy. Clinical trial registration: https://www.clinicaltrials.gov/, identifier NCT07112170.