Efficacy and Safety of SBRT Combined With Cardonilizumab and Lenvastinib in the Treatment of Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

Phase 1

Recruiting

• Conditions: Portal Vein Tumor Thrombus; Immune Checkpoint Inhibitors; Hepatocellular Carcinoma Non-resectable
• Interventions: Drug: Cadonilimab; Radiation: Stereotactic radiotherapy; Drug: Renvatinib

• Registration Number: NCT06040177
• Lead Sponsor: First Affiliated Hospital of Guangxi Medical University

Brief Summary

This study is a single-arm, multicenter clinical study to evaluate the efficacy and safety of SBRT combined with cardonilizumab and lenvastinib in the treatment of unresectable hepatocellular carcinoma with portal vein tumor thrombus

Detailed Description

Not available

Study Timeline

• Study Start: 2023-02-02
• Primary Completion: 2023-02-02
• Study First Submitted: 2023-07-13
• Status Verified: 2023-09
• Study First Submitted QC: 2023-09-13
• Last Update Submitted: 2023-09-13
• Study First Posted: 2023-09-15
• Last Update Posted: 2023-09-15
• Study Completion: 2025-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Age: 18-70 years old;

2. Eastern Cooperative Oncology Group (ECOG) -Performance Status(PS):0-2 points；

3. Hepatocellular carcinoma was diagnosed according to histopathology or the 2022 diagnostic criteria for primary liver cancer；

4. Expected survival period≥3 months;

5. Liver function grade Child-Pugh A or better grade B (7 points);

6. At least one measurable lesion:

   Liver lesion ① The Lesion can be accurately measured at least in the range of 1.0cm;

   ② The Lesion is suitable for repeated measurement;

   • The lesion shows enhanced intratumoral arteries on computed tomography (CT) or magnetic resonance imaging (MRI); Non-liver lesion In at least one dimension, the short axis of lymphadenopathy (LN) is≥1.5cm. Longest diameter of non-nodular lesions is≥1.0cm

7. The Barcelona liver cancer staging system is stage C (BCLC-C), which meets one of the following conditions:

(1) Liver tumor can be resected, which is combined with Vp 3-4 portal vein cancer thrombus; (2) Liver tumor is unresectable or has distant metastasis, and is combined with Vp1-4 type portal vein cancer thrombus; 8. The patient had not received prior systemic therapy including sorafenib, lenvatinib, chemotherapy; 9. The patient had previously received locoregional therapy (including radiofrequency or ablation therapy, percutaneous ethanol or acetic acid injection, cryotherapy, high intensity focused ultrasound, hepatic artery chemoembolization, hepatic artery embolization, etc., and the local treatment area had definite progression (according to RECIST v1.1 criteria); 10. Baseline blood routine and biochemical indicators meet the following criteria: Hemoglobin≥90g / L; Absolute neutrophil count (ANC)≥1.5× 10 ^ 9 / L; Platelet≥75×10 ^ 9 / L; ALT,AST ≤3×upper normal value (ULN); Serum total bilirubin ≤ 1.5 ×ULN; Serum creatinine ≤1.5 × ULN; Serum albumin was used for≥30g / L.

Exclusion Criteria

1. Patients diagnosed with hepatobiliary duct cell carcinoma, mixed cell carcinoma, or fibrolaminar cell carcinoma；
2. Patients with a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation or planned transplantation；
3. Patients have hepatic encephalopathy (West Haven Standard Grade III, Level IV) or have moderate or severe ascites (i.e., patients requiring therapeutic puncture drainage) or have uncontrolled pleural or pericardial effusion；
4. Patients have symptomatic, untreated, or progressive central nervous system (CNS) or leptomeningeal metastases.If all the following criteria are met, asymptomatic subjects with treated CNS lesions can be enrolled.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SBRT+cardonilizumab+lenvastinib Group	Renvatinib	Renvatinib: 8mg (weight \<60kg) or 12mg (weight ≥60kg) once a day until disease progression, intolerable toxicity Radiation therapy: Stereotactic radiotherapy (5-8Gy\*5F) for portal vein thrombus within 21 days after entry Cadonilimab will be administered within 2 weeks after the completion of the radiotherapy treatment once every 3 weeks (Q3W), for up to 2 years
SBRT+cardonilizumab+lenvastinib Group	Cadonilimab	Renvatinib: 8mg (weight \<60kg) or 12mg (weight ≥60kg) once a day until disease progression, intolerable toxicity Radiation therapy: Stereotactic radiotherapy (5-8Gy\*5F) for portal vein thrombus within 21 days after entry Cadonilimab will be administered within 2 weeks after the completion of the radiotherapy treatment once every 3 weeks (Q3W), for up to 2 years
SBRT+cardonilizumab+lenvastinib Group	Stereotactic radiotherapy	Renvatinib: 8mg (weight \<60kg) or 12mg (weight ≥60kg) once a day until disease progression, intolerable toxicity Radiation therapy: Stereotactic radiotherapy (5-8Gy\*5F) for portal vein thrombus within 21 days after entry Cadonilimab will be administered within 2 weeks after the completion of the radiotherapy treatment once every 3 weeks (Q3W), for up to 2 years

Primary Outcome Measures

Name	Time	Method
Objective response rate(ORR)	Up to approximately 2 years	ORR is proportion of patients with complete response(CR) or partial response(PR) assessed by investigators according to RECIST v1.1.

Secondary Outcome Measures

Name	Time	Method
3-month PFS rate	Up to approximately 2 years	3-month PFS rate is the percentage of patients whose disease has not progressed within 3 months.
progression-free survival (PFS)	Up to approximately 2 years	Progression-free survival (PFS) is defined as the time from the first dose of Cadonilimab until documentation of PD (as per RECIST v1.1) or death due to any cause, whichever occurs first.
Disease control rate (DCR)	Up to approximately 2 years	DCR is proportion of patients with complete response, partial response or stable disease assessed by investigators according to RECIST v1.1.
Duration of response (DOR)	Up to approximately 2 years	Duration of Response (DOR) is defined as the time between the first assessment of a tumor as Complete Response（CR）or Partial Response（PR）and the first assessment of Progressive Disease (PD) or death from any cause.
Overall Survival (OS)	Up to approximately 2 years	Overall survival (OS) is defined as the time from the first dose of Cadonilimab until death due to any cause

Trial Locations

Locations (1)

First Affiliated Hospital of Guangxi Medical University; 🇨🇳 Nanning, Guangxi, China