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

Study Overview
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Brief Summary
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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

Official Title
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Efficacy and Safety of SBRT Combined With Cardonilizumab and Lenvastinib in the Treatment of Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus#a Prospective, Multicenter, Single-arm Clinical Study

Conditions
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Hepatocellular Carcinoma Non-resectable, Portal Vein Tumor Thrombus, Immune Checkpoint Inhibitors

Intervention / Treatment
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* Drug: Cadonilimab
* Radiation: Stereotactic radiotherapy
* Drug: Renvatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-70 years old; Eastern Cooperative Oncology Group (ECOG) -Performance Status(PS):0-2 points； Hepatocellular carcinoma was diagnosed according to histopathology or the 2022 diagnostic criteria for primary liver cancer； Expected survival period≥3 months; Liver function grade Child-Pugh A or better grade B (7 points); 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 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: Patients diagnosed with hepatobiliary duct cell carcinoma, mixed cell carcinoma, or fibrolaminar cell carcinoma； Patients with a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation or planned transplantation； 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； 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SBRT+cardonilizumab+lenvastinib Group<br>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 | Drug: Cadonilimab<br>* Cadonilimab will be administered within 2 weeks after the completion of the radiotherapy treatment once every 3 weeks (Q3W), for up to 2 years<br>* Other names: AK104;Radiation: Stereotactic radiotherapy<br>* Radiation therapy: Stereotactic radiotherapy (5-8Gy*5F) for portal vein thrombus within 21 days after entry<br>Drug: Renvatinib<br>* Renvatinib: 8mg (weight <60kg) or 12mg (weight 60kg) once a day until disease progression, intolerable toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate(ORR) | ORR is proportion of patients with complete response(CR) or partial response(PR) assessed by investigators according to RECIST v1.1. | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-month PFS rate | 3-month PFS rate is the percentage of patients whose disease has not progressed within 3 months. | Up to approximately 2 years | 
| progression-free survival (PFS) | 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. | Up to approximately 2 years | 
| Disease control rate (DCR) | DCR is proportion of patients with complete response, partial response or stable disease assessed by investigators according to RECIST v1.1. | Up to approximately 2 years | 
| Duration of response (DOR) | 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. | Up to approximately 2 years | 
| Overall Survival (OS) | Overall survival (OS) is defined as the time from the first dose of Cadonilimab until death due to any cause | Up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, portal vein tumor thrombus, Immune Checkpoint Inhibitors, Efficacy