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

Summary

This multicenter, prospective, randomized, controlled, open-label, two-arm Phase III clinical trial is designed to evaluate whether adding radiotherapy to oligoprogressive lesions while continuing first-line systemic therapy at the time of oligoprogression can effectively prolong progression-free survival compared to early switching to second-line systemic therapy in oligoprogressive hepatocellular carcinoma.

Timeline

Start

2025-07-21

Primary completion

2027-07-01

Completion

2028-07-01

Publications

• Background Leng B, Wang H, Ge Y, Sun X, Dong P, Dong X, Duan X, Wang Q, Xia Y, Ding L, Dai H, Liu T, Shi F, Zhang X, Yue J. Maintaining First-Line Therapy Plus Radiation Therapy May Prolong Progression-Free Survival and Delay Second-Line Therapy for Oligoprogressive Hepatocellular Carcinoma. Int J Radiat Oncol Biol Phys. 2025 Jun 1;122(2):325-338. doi: 10.1016/j.ijrobp.2024.12.039. Epub 2025 Jan 15.
• Background Choi SH, Lee BM, Kim J, Kim DY, Seong J. Efficacy of stereotactic ablative radiotherapy in patients with oligometastatic hepatocellular carcinoma: A phase II study. J Hepatol. 2024 Jul;81(1):84-92. doi: 10.1016/j.jhep.2024.03.003. Epub 2024 Mar 11.
• Background Doyle E, Killean AJ, Harrow S, Phillips ID. Systematic review of the efficacy of stereotactic ablative radiotherapy for oligoprogressive disease in metastatic cancer. Radiother Oncol. 2024 Jul;196:110288. doi: 10.1016/j.radonc.2024.110288. Epub 2024 Apr 20.
• Background Tan VS, Padayachee J, Rodrigues GB, Navarro I, Shah PS, Palma DA, Barry A, Fazelzad R, Raphael J, Helou J. Stereotactic ablative radiotherapy for oligoprogressive solid tumours: A systematic review and meta-analysis. Radiother Oncol. 2024 Nov;200:110505. doi: 10.1016/j.radonc.2024.110505. Epub 2024 Aug 26.
• Background Wang Q, Yu J, Sun X, Li J, Cao S, Han Y, Wang H, Yang Z, Li J, Hu C, Zhang Y, Jin L. Sequencing of systemic therapy in unresectable hepatocellular carcinoma: A systematic review and Bayesian network meta-analysis of randomized clinical trials. Crit Rev Oncol Hematol. 2024 Dec;204:104522. doi: 10.1016/j.critrevonc.2024.104522. Epub 2024 Sep 26.
• Background Cappuyns S, Corbett V, Yarchoan M, Finn RS, Llovet JM. Critical Appraisal of Guideline Recommendations on Systemic Therapies for Advanced Hepatocellular Carcinoma: A Review. JAMA Oncol. 2024 Mar 1;10(3):395-404. doi: 10.1001/jamaoncol.2023.2677.
• Background Llovet JM, Castet F, Heikenwalder M, Maini MK, Mazzaferro V, Pinato DJ, Pikarsky E, Zhu AX, Finn RS. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 2022 Mar;19(3):151-172. doi: 10.1038/s41571-021-00573-2. Epub 2021 Nov 11.
• Background Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013 Nov;19(11):1423-37. doi: 10.1038/nm.3394.
• Wang H, Shi F, Zhang X, Zhu K, Jiang S, Feng R, Dou X, Xu L, Yue J. Continuation of first-line therapy with radiotherapy for oligoprogression versus early switch to second-line therapy in oligoprogressive hepatocellular carcinoma (CROSS): study protocol of a multicentre, randomised, controlled, open-label, phase III trial. BMJ Open. 2026 Jun 9;16(6):e118739. doi: 10.1136/bmjopen-2026-118739.

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Indications