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

• ClinicalTrials.gov Identifier: NCT06040177
• Recruitment Status: Recruiting
• First Posted: September 15, 2023
• Last Update Posted: September 15, 2023
• Sponsor: First Affiliated Hospital of Guangxi Medical University
• Information provided by (Responsible Party): Jie Ma, First Affiliated Hospital of Guangxi Medical University

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 (Clinical Trial)
• Estimated 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: February 2, 2023
• Actual Primary Completion Date: February 2, 2023
• Estimated Study Completion Date: February 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 Name: 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 :

1. Objective response rate(ORR) [ Time Frame: 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 :

1. 3-month PFS rate [ Time Frame: Up to approximately 2 years ]
   3-month PFS rate is the percentage of patients whose disease has not progressed within 3 months.
2. progression-free survival (PFS) [ Time Frame: 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.
3. Disease control rate (DCR) [ Time Frame: 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.
4. Duration of response (DOR) [ Time Frame: 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.
5. Overall Survival (OS) [ Time Frame: 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

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Ning Mo, professor; 15289662269; 369895025@qq.com

Locations

China, Guangxi

First Affiliated Hospital of Guangxi Medical University; Recruiting

Nanning, Guangxi, China

Contact: ning mo 15289662269 369895025@qq.com

Sponsors and Collaborators

First Affiliated Hospital of Guangxi Medical University

More Information

• Responsible Party: Jie Ma, Clinical Professor, First Affiliated Hospital of Guangxi Medical University
• ClinicalTrials.gov Identifier: NCT06040177
• Other Study ID Numbers: GuangxiMUMJ1
• First Posted: September 15, 2023
• Last Update Posted: September 15, 2023
• Last Verified: September 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jie Ma, First Affiliated Hospital of Guangxi Medical University:

Hepatocellular Carcinoma; portal vein tumor thrombus; Immune Checkpoint Inhibitors; Efficacy

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Thrombosis; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases