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| Name | Class |
|---|---|
| Beijing Bethune Charitable Foundation | UNKNOWN |
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This study is designed to evaluate the efficacy and safety of sintilimab-bevacizumab doublet combined with FOLFOX-HAIC and TACE as the perioperative adjuvant therapy in surgical resection to hepatocellular carcinoma with high-risk features. (1) Evaluate for some high-risk patients with resectable tumours, whether or not sintilimab-bevacizumab doublet combined with FOLFOX-HAIC and TACE reduces the risk of recurrence and improves the survival of patients. (2) Evaluate the safety of sintilimab-bevacizumab doublet combined with FOLFOX-HAIC and TACE for the neoadjuvant therapy of resectable hepatocellular carcinoma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A( Intervention group) | Experimental | 2-4 cycles of quadruple therapy (3 weeks per cycle) consisting of neoadjuvant FOLFOX-HAIC (oxaliplatin 85 mg/m² intra-arterial infusion over 2 hours; leucovorin calcium 200 mg/m² intra-arterial infusion over 2 hours; 5-fluorouracil 400 mg/m² intra-arterial bolus followed by 2400 mg/m² continuous intra-arterial infusion over 46 hours) sequentially combined with cTACE, sintilimab (200 mg intravenous infusion, q3w) and bevacizumab (15 mg/kg intravenous infusion, q3w). Tumor response was evaluated every 2 cycles, and radical resection was performed based on assessment results. After radical hepatectomy, patients continued to receive sintilimab plus bevacizumab for 8 cycles within 4-12 weeks postoperatively. |
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| Group B ( Control group) | Other | hepatectomy, and sintilimab was administered for 8 cycles with in 4 to 12 weeks after hepatectomy |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FOLFOX regimen | Drug | oxaliplatin 85 mg/m² intra-arterial infusion over 2 hours; leucovorin calcium 200 mg/m² intra-arterial infusion over 2 hours; 5-fluorouracil 400 mg/m² intra-arterial bolus followed by 2400 mg/m² continuous intra-arterial infusion over 46 hours |
| Measure | Description | Time Frame |
|---|---|---|
| 2y-RFS | 2-year recurrence-free survival rate | From date of randomization until date of first documented recurrence or death from any cause, whichever occurs first, assessed up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| pCR | pathological Complete Response,defined as the absence of residual invasive tumor cells in the primary tumor and regional lymph nodes in the resected specimen after neoadjuvant therapy. | Perioperative |
| MPR |
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Inclusion Criteria:
1.Fully understanding and voluntarily signing the informed consent form, complying with the requirements and evaluation schedule of this study; 2.18 to 75 years old; 3.Hepatocellular carcinoma diagnosed by histopathology; 4.Imaging examination results meeting the definition of high-risk recurrence risk factors in this study: 2-4 multiple tumors; the size of the dominant tumor was >=5 cm; CNLC-Ⅲa incorporated with portal vein tumor thrombus [Vp1/2/3]; 5.Surgical evalution with a radically resectable tumor; 6.Child-Pugh class A; 7.ECOG PS: 0~1; 8.hepatocellular carcinoma who had never received previous form of systemic therapy; 9.At least one measurable lesion that can be accurately assessed by computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for assessment per mRECIST 1.1; 10.The main organ functions are normal, including the following criteria: (1) sufficient bone marrow function, defined as neutrophils ≥ 1.5 × 10 ^ 9/L, hemoglobin (Hb) ≥ 90 g/dL, platelets ≥ 50 × 10 ^ 9/L; (2) good liver function, defined as serum total bilirubin ≤ 1.5 × ULN, aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN, albumin ≥ 28 g/L; (3) good coagulation function, defined as international normalized ratio (INR) ≤ 2.3 or prothrombin time (PT) exceeding the normal control range ≤ 3 seconds; (4) Adequate renal function, defined as glomerular filtration rate (GFR)>90mL/min; 11.Female participants of childbearing potential have negative results on a pregancy test in 3 days before the first utilization of medicine and male or female participants with partners of child-bearing potential had to use a medically acceptable method of contraception through 180 days after taking study drug
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| BinYong Liang, M.D. | Contact | 8615927271139 | Binyong.liang@tjh.tjmu.edu.cn |
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| Immunotherapy | Drug | sintilimab (200 mg intravenous infusion, q3w) |
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| targeted therapy | Drug | bevacizumab (15 mg/kg intravenous infusion, q3w) |
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| cTACE | Device | conventional transarterial chemoembolization |
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Major Pathological Response,presence of viable tumor cells ≤30% in the primary tumor and lymph nodes after radical resection
| Perioperative |
| ORR | Objective Response Rate,the proportion of patients who achieved complete response (CR) or partial response (PR) in tumor shrinkage according to the mRECIST v1.1 criteria and maintained the response for at least 8 weeks | Perioperative |
| R0 resection rate | The proportion of patients who achieved radical R0 resection among those who underwent surgery. | Perioperative |
| EFS | Event-Free Survival, defined as the time from randomization to the first occurrence of any of the following events: disease progression precluding surgery, local or distant recurrence, or death from any cause. | the time from randomization to the first occurrence of any of the following events: disease progression precluding surgery, local or distant recurrence, or death from any cause,assessed up to 2 years |
| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
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| ID | Term |
|---|---|
| C410216 | Folfox protocol |
| D007167 | Immunotherapy |
| C000632826 | sintilimab |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D056747 | Immunomodulation |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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