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

Sponsor

First Affiliated Hospital of Guangxi Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT06040177

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma Non-resectable Portal Vein Tumor Thrombus Immune Checkpoint Inhibitors	Drug: Cadonilimab Radiation: Stereotactic radiotherapy Drug: Renvatinib	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 2, 2023

Actual Primary Completion Date :

Feb 2, 2023

Anticipated Study Completion Date :

Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SBRT+cardonilizumab+lenvastinib Group 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 Cadonilimab will be administered within 2 weeks after the completion of the radiotherapy treatment once every 3 weeks (Q3W), for up to 2 years Other Names: AK104 Radiation: Stereotactic radiotherapy Radiation therapy: Stereotactic radiotherapy (5-8Gy5F) for portal vein thrombus within 21 days after entry Drug: Renvatinib* Renvatinib: 8mg (weight <60kg) or 12mg (weight 60kg) once a day until disease progression, intolerable toxicity

Arm

Intervention/Treatment

Experimental: SBRT+cardonilizumab+lenvastinib Group

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

Cadonilimab will be administered within 2 weeks after the completion of the radiotherapy treatment once every 3 weeks (Q3W), for up to 2 years

Other Names:

AK104

Radiation: Stereotactic radiotherapy

Radiation therapy: Stereotactic radiotherapy (5-8Gy*5F) for portal vein thrombus within 21 days after entry

Drug: Renvatinib

Renvatinib: 8mg (weight <60kg) or 12mg (weight 60kg) once a day until disease progression, intolerable toxicity

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.