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

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

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

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma Non-resectable; Immune Checkpoint Inhibitors; Portal Vein Tumor Thrombus
• Intervention / Treatment: Drug: Cadonilimab; Radiation: Stereotactic radiotherapy; Drug: Renvatinib

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ning Mo, professor; Phone Number: 15289662269; Email: 369895025@qq.com

Study Locations

• China
  • Guangxi
    • Nanning, Guangxi, China
      • Recruiting
      • First Affiliated Hospital of Guangxi Medical University
      • Contact: ning mo; Phone Number: 15289662269; Email: 369895025@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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
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
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
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

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Guangxi Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2023
• Primary Completion (Actual): February 2, 2023
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: July 13, 2023
• First Submitted That Met QC Criteria: September 13, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Efficacy; Immune Checkpoint Inhibitors; portal vein tumor thrombus
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Embolism and Thrombosis; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Thrombosis
• Other Study ID Numbers: GuangxiMUMJ1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No