NCT06524466

Neoadjuvant SBRT Combined With Lenvatinib and Pucotenlimab for Resectable Hepatocellular Carcinoma

Neoadjuvant Stereotactic Body Radiotherapy (SBRT) Combined With Lenvatinib and Pucotenlimab for Resectable Hepatocellular Carcinoma With Macrovascular Invasion: A Single-arm, Phase II Study

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

At the time of diagnosis, the majority of hepatocellular carcinoma (HCC) patients are at the intermediate to advanced stages, with a 50-70% incidence of macrovascular invasion (including portal vein, hepatic vein, inferior vena cava, or bile duct invasion). Tyrosine kinase inhibitors (TKI, including lenvatinib and sorafenib) or a combination of TKIs and immune therapy is one of the standard treatment options recommended by HCC guidelines. However, numerous retrospective studies have reported that for surgically resectable HCC with macrovascular invasion, surgical resection yields better efficacy than non-surgical treatments (including transarterial interventional therapies and/or systemic therapies). Nevertheless, the postoperative recurrence rate remains exceedingly high, exceeding 80%. Therefore, determining comprehensive approaches to enhance surgical radicality and reduce postoperative recurrence rates is a current research hotspot. Recent studies have found that neoadjuvant therapy (including immunotherapy alone or in combination with TKI) before surgery can reduce postoperative recurrence rates and extend survival rates. Moreover, SBRT combined with TKI and immunotherapy has a sensitizing effect, particularly showing good sensitivity and control rates for vascular invasion. Thus, this study aims to conduct a prospective, single-arm phase II clinical trial targeting patients with surgically resectable HCC with macrovascular invasion. The primary endpoints are objective response rate (ORR) and treatment completion rate, to evaluate the efficacy and safety of the preoperative neoadjuvant therapy with the combination of SBRT, lenvatinib, and pucotenlimab (an anti PD-1 drug). The secondary endpoints include progression-free survival (PFS), overall survival (OS), incidence of adverse events, pathological response rate, and incidence of surgical complications, to preliminarily evaluate the efficacy of the neoadjuvant therapy with this triple regimen.

Conditions

• Resectable Hepatocellular Carcinoma
• Macrovascular Invasion
• CNLC IIIA Stage

Interventions

Type	Name	Description
DRUG	Neoadjuvant SBRT combined with Lenvatinib and Pucotenlimab	SBRT: SBRT will be performed within 2-4 weeks after enrollment. The total radiation dose will be 24 Gy, delivered in 3 fractions on alternate days, to be completed within one week. Lenvatinib: 8mg/day, begin immediately after enrollment. Lenvatinib should be discontinued one week before surgery. Pucotenlimab: 200mg，3-week interval between cycles, begin immediately after enrollment, a total of four cycles of Puco treatment must be completed before surgery. Surgical resection will be performed within 10-16 weeks after the completion of SBRT.

Timeline

• Start date: 2024-07-23
• Primary completion: 2026-12-01
• Completion: 2026-12-01
• First posted: 2024-07-29
• Last updated: 2024-07-29

Locations

1 site across 1 country: China