Hepatocellular carcinoma
Conditions
Interventions
Neoadjuvant therapy group:Preoperative lenvatinib combined with sintilimab
Adjuvant therapy group:Postoperative lenvatinib combined with sintilimab
Sponsors
Beijing Youan Hospital, Capital Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1.Voluntary enrollment with written informed consent obtained; 2.Age 18–80 years (inclusive), both sexes eligible 3.Clinically diagnosed or histologically/cytologically confirmed hepatocellular carcinoma (HCC); 4.Newly diagnosed HCC, or HCC with new lesions appearing =2 years after curative-intent therapy, is allowed; 5.Liver lesion(s) deemed resectable with adequate future liver remnant and presence of high-risk recurrence factors: CNLC stage ?a–?a: ill-defined tumor margin or incomplete capsule, or anticipated resection margin 3 tumors, largest tumor >5 cm, or macrovascular invasion; CNLC ?b: tumor(s) confined to the same segment or ipsilateral hemiliver, or amenable to simultaneous intra-operative ablation of extra-resection lesions; CNLC ?a: tumor(s) confined to the same segment or ipsilateral hemiliver with portal vein tumor thrombus grade 1–2 (Vp1–2), or resectable bile-duct tumor thrombus, or peripheral hepatic-vein tumor thrombus (Vv1) allowing R0 resection. 6.No prior systemic anticancer therapy or other locoregional treatment; 7.At least one measurable lesion per RECIST 1.1; 8.ECOG performance status 0–1; 9.Child-Pugh score =90 g/L Absolute neutrophil count >=1.5×10^9/L Platelet count >=75×10^9/L Biochemistry: Albumin >=28 g/L Total bilirubin <=3×ULN ALT and AST <=5×ULN ALP <=5×ULN Creatinine <=1.5×ULN Coagulation: INR or PT <=1.5×ULN; APTT <=1.5×ULN 11.If HBsAg(+) and/or anti-HCV(+), antiviral therapy must be given per standard guidelines based on HBV DNA or HCV RNA results; 12.Women of child-bearing potential must have a negative serum/urine pregnancy test within 14 days before enrollment, must not be breastfeeding, and must agree to use effective contraception from enrollment through 60 days after the last dose; men must use effective contraception during the same period; 13.Good compliance and willingness to attend follow-up visits.
Exclusion criteria
Exclusion criteria: 1.Prior histological/cytological diagnosis of fibrolamellar or sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, or any mixed hepatic malignancy; 2.History of malignancy other than hepatocellular carcinoma, unless: (1) Curative-intent treatment was given and no evidence of disease for >=5 years; or (2) Adequately treated basal-cell or squamous-cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or other carcinoma in situ. 3.Diffuse, infiltrative hepatic tumor; 4.Extrahepatic metastasis, or tumor thrombus in the main portal vein, superior mesenteric vein, or inferior vena cava; 5.Prior hepatic encephalopathy or hepatorenal syndrome; 6.Congenital or acquired immunodeficiency syndrome; 7.Severe psychiatric disorder, past or present; 8.Diseases that could impair absorption, distribution, metabolism, or excretion of study drugs (e.g., intractable vomiting, chronic diarrhea, intestinal obstruction, malabsorption); Concomitant or Prior Medications / Procedures 9.Previous allogeneic stem-cell or solid-organ transplantation. 10.Prior therapy with sorafenib, lenvatinib, donafenib, regorafenib, or other anti-VEGF/-VEGFR, RAF, MEK pathway inhibitors, or with anti–PD-1, anti–PD-L1, anti–CTLA-4, or any other immune-modulating biologics. Safety Exclusions 11.Known or suspected hypersensitivity to lenvatinib, sintilimab, their analogues, or any excipients. 12.Active bleeding, bleeding diathesis, or concurrent thrombolytic, anticoagulant, or antiplatelet therapy; 13.Thrombotic/thrombo-embolic event within 6 months (e.g., stroke/TIA, DVT, PE); 14.Esophageal or gastric variceal bleeding due to portal hypertension within 6 months, or any life-threatening hemorrhage within 3 months; 15.Clinically significant cardiovascular disease: acute MI, severe/unstable angina, or CABG within 6 months; congestive heart failure (NYHA class >2); uncontrolled arrhythmia requiring pacemaker; hypertension not adequately controlled (systolic >=140 mmHg or diastolic >=90 mmHg on medication); 16.Other clinically important laboratory or medical abnormalities that, in the investigator’s opinion, could compromise safety assessment—e.g., uncontrolled diabetes, chronic kidney disease, grade >=2 peripheral neuropathy (CTCAE v5.0), thyroid dysfunction. 17.Active or poorly controlled serious infection. Incomplete recovery from surgery (unhealed incision, major post-operative complications).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1-year Recurrence-Free Survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Recurrence-Free Survival;2-year Recurrence-Free Survival;Overall Survival;Objective Response Rate;surgery rate;R0 resection rate;Health-Related Quality of Life; | — |
Countries
China
Contacts
Public ContactDaobing Zeng
Beijing Youan Hospital, Capital Medical University
Outcome results
None listed