Hepatocellular Carcinoma
Conditions
Brief summary
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.
Interventions
DRUGFOLFOX regimen
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
DRUGImmunotherapy
sintilimab (200 mg intravenous infusion, q3w)
DRUGtargeted therapy
bevacizumab (15 mg/kg intravenous infusion, q3w)
DEVICEcTACE
conventional transarterial chemoembolization
Sponsors
BinYong Liang
Beijing Bethune Charitable Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
1. Pregnant or lactating women; 2. Patients with a history of other malignancies within the past 5 years, excluding basal cell carcinoma of the skin， cervical carcinoma in situ and/or thyroid papillary carcinoma have been cured; 3. Patients who are known to be allergic to the trial drugs, finolizumab and bevacizumab； 4. Previous history of upper gastrointestinal bleeding or current presence of a clear bleeding risk disease; 5. Patients with uncontrolled cardiac clinical symptoms or diseases； 6. Uncontrolled cardiac symptoms or diseases, including but not limited to (1) heart failure above NYHA class II, (2) unstable angina, (3) myocardial infarction within 1 year, and (4) clinically important significant supraventricular or ventricular arrhythmias requiring clinical intervention； 7. Patients with any active autoimmune disease or history of autoimmune disease； 8. Have a history of immune deficiency, including HIV-positive test results, or suffer from other acquired or congenital immune deficiency diseases, or have a history of organ transplantation and bone marrow transplantation; 9. History of mental illness, and abuse of psychiatric drugs and narcotics; 10. Severe uncontrolled recurrent infections or other serious uncontrolled concomitant diseases; 11. Situations that researchers assessed as unsuitable for inclusion in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2y-RFS | From date of randomization until date of first documented recurrence or death from any cause, whichever occurs first, assessed up to 2 years | 2-year recurrence-free survival rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| pCR | Perioperative | 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. |
| MPR | Perioperative | Major Pathological Response，presence of viable tumor cells ≤30% in the primary tumor and lymph nodes after radical resection |
| ORR | Perioperative | 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 |
| R0 resection rate | Perioperative | The proportion of patients who achieved radical R0 resection among those who underwent surgery. |
| EFS | 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 | 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. |
Contacts
CONTACTBinYong Liang, M.D.
Outcome results
None listed