Phase 3 Trial Comparing Radiotherapy Plus Continued First-line Therapy Versus Early Switch to Second-line Therapy in Oligoprogressive Hepatocellular Carcinoma

What this Trial Is About

This research aims to evaluate treatment options for patients with oligoprogressive hepatocellular carcinoma HCC who are receiving first-line systemic therapy. HCC is often diagnosed late due to its aggressive nature and lack of early symptoms, limiting curative options. The study compares whether adding radiotherapy to treat limited progressing lesions while continuing first-line therapy can extend progression-free survival compared to switching early to second-line systemic therapy. This is a multicenter, randomized, controlled, open-label Phase III trial. Participants will be assigned to one of two groups one group will continue their current first-line systemic therapy, which may include combinations like atezolizumab plus bevacizumab or monotherapies such as lenvatinib or sorafenib, combined with radiotherapy targeting the progressing lesions. Radiotherapy will use techniques such as 3D-CRT, IMRT, or IGRT with a biologically effective dose of at least 60 Gy, adjusted by tumor location and size. The other group will switch early to second-line systemic therapy, individualized by a multidisciplinary team based on prior treatment and patient condition. During the study, participants will have regular assessments including imaging to confirm progression, tumor and blood sample collection for biomarker analysis, and monitoring for adverse events. The primary outcome is progression-free survival measured over two years, with secondary outcomes including overall survival, response rates, and safety over up to five years. Follow-up includes evaluation of circulating tumor DNA and optional biopsies to explore molecular changes. Participants are expected to comply with treatment and follow-up visits throughout the study duration.

Continuation of First-line Therapy With Radiotherapy Versus Early Switch to Second-line Therapy in Oligoprogressive HCC