Sintilimab and Bevacizumab Combined With Radiotherapy for Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to investigate both the efficacy and safety of sintilimab combined with bevacizumab and radiotherapy in advanced hepatocellular carcinoma.

Official Title
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Sintilimab and Bevacizumab Combined With Radiotherapy in the Treatment of Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Sintilimab and Bevacizumab Combined with Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Treatment-naïve primary HCC (consistent with the American Association for the Study of Liver Diseases 2018 Guideline on Liver Cancer Diagnosis (18)) or initial recurrent HCC after radical resection without any postoperative anti-cancer treatment; At least one measurable lesion in the liver on the basis of modified Response Evaluation Criteria in Solid Tumors (mRECIST); Presented with Cheng's type I/II/III PVTT; Largest tumor size ≤ 10 cm, number of tumors ≤ 3, and remnant liver volume ≥ 50%; Child-Pugh class A; Adequate hematological, liver, renal function: hemoglobin concentration ≥ 90 g/L; neutrophil count ≥ 1.5×109/L; platelet count ≥ 60×109/L; AST and ALT ≤ 3×upper limit of normal (ULN) total bilirubin ≤ 1.5×ULN; serum creatinine ≤ 1.5×ULN; serum albumin concentration ≥ 30 g/L; Life expectancy of at least 3 months. Exclusion Criteria: Tumor invasion of the superior mesenteric vein or bile ducts; Infiltrative HCC; Allergic to research reagents; With other malignancies within 5 years; With poorly controlled hypertension; A past medical history of hepatic decompensation, such as hepatic encephalopathy, refractory ascites, and esophageal or gastric variceal bleeding; A history of autoimmune disease; Active infection requiring systemic treatments; Severe bleeding; With diseases needing daily non-steroidal anti-inflammatory drug (NSAID) therapy; With other severe comorbidities.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Sintilimab and Bevacizumab Combined with Radiotherapy<br> | Drug: Sintilimab and Bevacizumab Combined with Radiotherapy<br>* Before radiotherapy: Bevacizumab+Sintilizumab, Q3w, 2 cycles in total. Radiation therapy: 30-50Gy/10 fractions. After radiotherapy: Bevacizumab+Sintilizumab, Q3w until disease progression or toxicity is intolerable.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR (objective response rate) | the proportion of patients who have a partial or complete response to therapy. | through study completion, up to 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS (progression-free survival) | defined as the time from receiving treatment until disease progression or death from any cause, whichever happens first. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive and progression free. Patients not having an event will be censored at the date last seen alive. | through study completion, up to 2 year | 
| OS (overall survival) | defined as the time from receiving treatment until death from any cause. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive. Patients remaining alive throughout the duration of the study will have their survival time censored on the date last seen alive. | through study completion, up to 2 year | 
| DCR (disease control rate) | the proportion of patients whose tumors have shrunk or been stable for a certain period of time, including cases of complete response (CR), partial response (PR), or stable disease (SD). | through study completion, up to 2 year | 
| LCR (local control rate) | the percentage of lesions with absence of recurrence within the high-dose region （80% isodose volume） | through study completion, up to 2 year | 
| Adverse effects | Adverse effects of sintilimab and bevacizumab combined with radiotherapy,number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | through study completion, up to 2 year |