NCT04988945

TACE and SBRT Followed by Double Immunotherapy for Downstaging Hepatocellular Carcinoma

Sequential TransArterial Chemoembolization and Stereotactic RadioTherapy Followed by Durvalumab (MEDI4736) and Tremelimumab for Downstaging Hepatocellular Carcinoma for Hepatectomy

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Sponsor: The University of Hong Kong · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is a prospective phase II, single arm mono-institutional study conducted in Queen Mary Hospital (Hong Kong) assessing the efficacy and safety of the sequential administration of trans-arterial chemo-embolization (TACE) and stereotactic body radiotherapy (SBRT) with immune checkpoint inhibitors in unresectable hepatocellular carcinoma (HCC) patients.

Detailed description

Hepatocellular carcinoma (HCC) is a serious global health problem. It ranks the fifth in incidence and third in cancer-related mortality at Hong Kong in 2015. The disease has high mortality rate, and surgery is the only curative therapy although only 30% of patients are diagnosed early enough to undergo liver resection or transplantation or radiofrequency ablation (RFA). For inoperable patients with disease limited to liver, trans-arterial chemo-embolization (TACE) is the most commonly used therapy. Previous randomized studies have demonstrated its survival benefit, however it rarely cures the disease; also its efficacy is very limited in patients with sizable tumor or multi-focal diseases. Efforts have been made to improve the response of treatment, but none has consistently demonstrated the benefit. As a result, over the past decade, there is no major advancement in the treatment strategy for intermediate stage HCC patients. Recently, stereotactic body radiotherapy (SBRT) has emerged as one of the promising local therapy of HCC. This advanced radiotherapy technique allows killing of cancer cells by delivering a potent dose of radiation with excellent geometric precision. Data have demonstrated its favorable local control rate and toxicity profile in locally advanced HCC. Further, recent studies, including our series, indicated that combining SBRT and TACE is therapeutically superior. As such, it is postulated that combined TACE+SBRT is a more potent local therapy than TACE in preventing tumor progression, and it may potentially translate into survival benefit. The recent discovery in immune-oncology represents another breakthrough in management of HCC. Pre-clinical data showed that there is high expression of immunosuppressive cells and up-regulation of programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) immune checkpoints in the HCC microenvironment; it provides the rationale for immunotherapy to be used in this setting. This premise was supported by several early phase clinical studies, in which anti-PD-1/programmed death ligand 1 (PD-L1) therapy resulted in a durable response and favorable survival. More intriguingly, there are scientific and clinical data in supporting the synergy between immune checkpoint inhibitors (ICI) and SBRT for both local tumor regression and distant control (out-of-the-field abscopal) effect. For high risk HCC, such approach may warrant further exploration. Based on all these, a hypothesis is made that combined TACE+SBRT followed by immunotherapy is a promising strategy in treating unresectable HCC. In this single-arm prospective phase II study, it is aimed at evaluating the efficacy and safety of this treatment regime.

Conditions

• HCC

Interventions

Type	Name	Description
PROCEDURE	TACE	Procedure of TACE will be standardized.
RADIATION	SBRT	SBRT screening and planning will be performed by radiation therapists, medical physicists, and oncologists.
DRUG	Durvalumab	1500mg Durvalumab administered IV over 60 minutes on Day 1 of each immunotherapy treatment every 4 weeks until disease progression (PD)
DRUG	Tremelimumab	300mg Tremelimumab administered over 60 minutes on Day 1 of cycle 1.

Timeline

• Start date: 2020-12-01
• Primary completion: 2024-12-01
• Completion: 2026-12-01
• First posted: 2021-08-04
• Last updated: 2023-09-06

Locations

2 sites across 1 country: Hong Kong