Early postoperative recurrent resectable hepatocellular carcinoma (HCC)
Conditions
Interventions
Experimental Group:Nivolumab 1 mg/kg+ Ipilimumab 3 mg/kg,Administered Q3W on Day 1 and Day 22,A total of 2 cycles
Sponsors
Zhongshan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Prior to any study protocol-related procedure, the subject or his or her legally authorized representative signed and dated a written ICF approved by the IRB/IEC. 2. Participants must be willing and able to comply with the prescribed visits, treatment schedules, laboratory tests, and other requirements of the study. 3. Male and female, aged >=18 years and=3 months. 5. Subjects had to have histologically or cytologically or clinically confirmed HCC. 6. During the screening period, subjects were asked to provide liver cancer tissue specimens (1 paraffin-embedded [FFPE] block or 20 unstained tumor tissue sections) that could provide primary surgical resection. 7. Patients had to have intrahepatic recurrence confirmed by imaging (contrast-enhanced CT or MRI) between 3 months and 2 years after primary hepatectomy. 8. The subjects must be evaluated by the investigators to meet the indications for repeat hepatectomy (referring to the Chinese expert consensus on the prevention and treatment of recurrence after hepatectomy for hepatocellular carcinoma (2020 edition)) : a) the general condition of the patients is good; b) Child-Pugh grade A liver function (see Appendix 3) with no or mild portal hypertension; c) no serious basic diseases of vital organs such as heart, lung and kidney; d) single, or multiple but =10 mm. Note: The short diameter of malignant lymph nodes must be >=15 mm. "b) The lesion must not have received prior surgery, radiation therapy, and/or locoregional therapy (e.g., RFA, PEI or PAI, cryoablation, HIFU, TACE, TAE, etc.)." 10. Eastern Cooperative Oncology Group performance-status score (ECOG PS; see Appendix 4) was 0. 11. Participants must have not previously received systemic immune checkpoint inhibitor therapy. 12. Have full organ and bone marrow function. Screening laboratory values must meet the following criteria and must be obtained within 7 days prior to enrollment (no administration of blood components, cell growth factors, albumin, or other corrective medications was allowed within 14 days of obtaining the laboratory test) : a) Adequate blood function: Absolute neutrophil count (ANC) >=1.5×10^9/L Platelet count (PLT) >=75×10^9/L hemoglobin (HGB) >=9.0 g/dL b) Adequate liver function: Serum total bilirubin (TBIL) =28 g/L alkaline phosphatase (ALP) =50 mL/min (calculated using the Cockcroft-Gault formula) and urine routine resul
Exclusion criteria
Exclusion criteria: 1.Histologically confirmed fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma-HCC. 2.Prior liver transplantation. 3.Presence of extrahepatic metastases or unresectable lesions confirmed by imaging within 1 month prior to enrollment. 4.Recurrence within less than 3 months after surgery. 5.Lesions assessed as unresectable. 6.Prior systemic antitumor therapy for recurrent HCC, including but not limited to immunotherapy (PD-1, PD-L1, CTLA-4 antibodies, or bispecific/combination antibodies). 7.Prior local therapy after recurrence, including transarterial chemoembolization (TACE), ablation (radiofrequency ablation, microwave ablation, cryoablation, etc.), or radiotherapy. 8.Active co-infection with hepatitis B and hepatitis C or hepatitis B and hepatitis D that is not effectively controlled. 9.Known human immunodeficiency virus (HIV)-positive history or known AIDS history, or currently receiving systemic corticosteroid therapy. Note: HIV testing must be performed at a locally authorized institution. 10.Active bacterial, fungal, or viral infection requiring systemic therapy within 1 week prior to enrollment. 11.History of hepatic encephalopathy (>= Grade 2, see Appendix 6 for hepatic encephalopathy grading) within 12 months prior to enrollment. 12.Clinically significant ascites, defined as: a)Ascites previously requiring treatment and ongoing prophylaxis, or b)Ascites currently requiring treatment. 13.Presence of portal hypertension with a history of bleeding from esophageal or gastric varices within 6 months prior to enrollment. 14.Uncontrolled cardiac clinical symptoms or diseases, including but not limited to: a)Uncontrolled hypertension despite optimal therapy, defined as systolic blood pressure >150 mmHg or diastolic blood pressure > 90 mmHg. b)History of congestive heart failure greater than New York Heart Association (NYHA) class II. c)Active coronary artery disease, unstable or newly diagnosed angina, or myocardial infarction within 6 months prior to screening. d)Arrhythmias requiring antiarrhythmic therapy other than ß-blockers or digoxin at screening. e)Cardiac valvular disease graded > Grade 2 according to CTCAE. f)QTc interval (Fridericia formula) > 480 ms on 2 consecutive ECGs. 15.Symptomatic or potentially interfering interstitial lung disease that may affect the detection or management of drug-related pulmonary toxicity. 16.History of gastrointestinal or non-gastrointestinal fistula or gastrointestinal perforation. 17.History of non-healing wounds or skin ulcers within 3 months prior to enrollment. 18.History of thrombotic or embolic events (excluding HCC tumor thrombus) within 6 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks) or pulmonary embolism. 19.History of any CTCAE Grade >= 3 hemorrhagic events within 8 weeks prior to enrollment, or currently receiving thrombolytic therapy. 20.Systemic treatment with corticosteroids (> 10 mg/day prednisone or equivalent) or other immunosuppressive agents within 14 days prior to study drug administration. 21.Immunological contraindications or concurrent severe autoimmune diseases where the investigator considers immune checkpoint inhibitor therapy to carry excessive risk, including but not limited to: a)Active severe autoimmune diseases (e.g., systemic lupus erythematosus, Sjögren’s syndrome, myasthenia gravis, ulcerative colitis, Crohn’s disease, refractory psoriasis, etc.) requiring medium- to high-dose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| MPR rate, defined as the proportion of patients with <=50% residual viable tumor cells in the tumor bed.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pathological complete response (pCR), defined as the proportion of patients with no residual viable tumor cells in the tumor bed.;ORR was defined according to RECIST v1.1 and mRECIST, respectively.;RFS, defined as the time from the completion date of reoperation to first radiographic or histologically confirmed recurrence or death from any cause, whichever occurred first.;OS, defined as the time from the start of randomization (or the start of treatment in a single-arm trial) to death from any cause.; | — |
Countries
China
Contacts
Public ContactGuoming Shi; Jian Zhou
Zhongshan Hospital, Fudan University
Outcome results
None listed