noperable/non-metastatic hepatocellular carcinoma
Conditions
Interventions
Experimental group:Treatment with CVM-1118 Combined with Sintilimab and Transarterial Chemoembolization (TACE)
Sponsors
Zhongshan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Age >= 18 years at the time of providing written informed consent; 2.Diagnosis of hepatocellular carcinoma (HCC): Confirmed by pathology or cytology, OR Meeting the clinical diagnostic criteria of the American Association for the Study of Liver Diseases (AASLD) (i.e., a hepatic lesion >= 1 cm demonstrated by cross-sectional multiphasic contrast-enhanced computed tomography [CT] or magnetic resonance imaging [MRI]); 3. No evidence of extrahepatic metastasis on any available imaging; 4.Not eligible for curative surgery, transplantation, or curative ablation therapy; 5.Eligible for transarterial chemoembolization (TACE), with an expected number of TACE procedures for local disease = 10 IU/mL or above the local laboratory lower limit of detection): May be enrolled if disease is stable or virologic response is achieved under antiviral therapy, AND agrees to receive antiviral treatment during the trial. 10. Patients with hepatitis C virus (HCV) infection who agree to receive antiviral treatment during the trial; 11.Adequate organ and bone marrow function, meeting the following laboratory criteria: Hematology: Absolute neutrophil count (ANC) >= 1.5 × 10^9/L ;Platelet count (PLT) >= 75 × 10^9/L Hemoglobin (HGB) >= 9.0 g/dL (without transfusion or erythropoietin [EPO]) Hepatic function: Total bilirubin (T-Bil) = 30 g/L Renal function: Estimated glomerular filtration rate (eGFR) >= 60 mL/min (calculated using the formula in Appendix 4) Coagulation: International normalized ratio (INR) = 12 weeks; 13.Male and female participants of childbearing potential must agree to use highly effective contraception from signing the informed consent form (ICF) until 6 months after the last dose of investigational product. Females of childbearing potential are defined as premenopausal women. All females of childbearing potential must have a negative pregnancy test result = 7 days before the first dose of investigational product; 14.Has provided written informed consent and is able to comply with all study visits and procedures as required by the protocol.
Exclusion criteria
Exclusion criteria: 1.Known hypersensitivity to the components of CVM-1118 or sintilimab, or history of severe allergic reaction to monoclonal antibodies; 2.Histologically or cytologically confirmed fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, etc; 3.Total volume of HCC lesions >= 50 % of the total liver volume; 4.Imaging during screening shows tumor thrombus in the main portal vein or first-order portal vein branches (i.e., with VP3 or VP4 portal vein tumor thrombus). 5.Meeting the indications for liver transplantation; 6.Prior treatment with anti-programmed cell death protein 1 (PD-1), anti-programmed death ligand 1 (PD-L1), or anti-programmed death ligand 2 (PD-L2) agents, or agents targeting other T-cell co-stimulatory or co-inhibitory receptors (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4]); 7.Prior local treatment to existing intrahepatic lesions (e.g., TACE, transarterial embolization [TAE], transarterial radioembolization [TARE], hepatic arterial infusion chemotherapy, or radiotherapy). Local treatment such as TACE/TAE is permitted if administered as part of a curative intent approach (e.g., combined with ablation or surgery) and only for lesions treated with curative intent; however, TACE/TAE alone as the sole therapy in prior curative treatment is not allowed; 8.Prior systemic anti-tumor therapy for HCC; 9.History of abdominal fistula, gastrointestinal (GI) perforation, refractory gastric ulcer not healed with treatment, or active GI bleeding within 6 months prior to enrollment; 10.History of hemorrhagic or thrombotic disorders, or use of anticoagulants requiring INR monitoring (e.g., warfarin or similar agents). Antiplatelet agents and low-molecular-weight heparin are permitted. 11.Clinically significant ascites on physical examination that cannot be controlled by medication; 12.Clinically diagnosed hepatic encephalopathy within 6 months prior to enrollment that is refractory to treatment; 13.Any medical contraindication precluding contrast-enhanced imaging (CT or MRI); 14.History of GI malabsorption, gastrointestinal anastomosis, or other conditions that may affect absorption of CVM-1118; 15.Presence of Grade >= 3 GI or non-GI fistula; 16.Clinically significant hemoptysis or tumor bleeding of any cause within 2 weeks before the first dose of investigational product; 17.Severe cardiovascular disease within 12 months before the first dose of investigational product, such as congestive heart failure = New York Heart Association (NYHA) Functional Class II (Appendix 5), unstable angina, myocardial infarction, stroke, or cardiac arrhythmia associated with hemodynamic instability; 18.Major liver surgery within 4 weeks before the first dose of investigational product; 19.Minor surgery within 7 days before the first dose of investigational product; 20.Presence of non-healed severe wounds, ulcers, or fractures; 21.Live vaccine within 30 days before the first dose of investigational product; 22.Currently participating in, or participation in another investigational drug / device trial within 4 weeks before the first dose of investigational product; 23.Diagnosis of an immunodeficiency disorder, or systemic glucocorticoid therapy (at a dose exceeding 10 mg/day prednisone equivalent) or other forms of immunosuppressive therapy within 7 days before the first dose of investigational product; 24.Active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, glucocorticoids
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR, RECIST 1.1); | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS);Duration of Response (DoR);Overall Survival (OS);Disease Control Rate (DCR);Objective Response Rate (mRECIST);Time to Progression; | — |
Countries
China
Contacts
Public ContactFan Jia
Zhongshan Hospital, Fudan University
Outcome results
None listed