Hepatocellular Carcinoma
Conditions
Interventions
Single Arm:TACE plus lenvatinib and PD-1 antibody
Sponsors
Shanghai Eastern Hepatobiliary Hospital
Eligibility
Sex/Gender
Male
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Unresectable HCC, confirmed by radiology, histology, or cytology; 2. Be willing and able to provide written informed consent for the trial; 3. Be 18 to 70 years of age on the day of signing informed consent; 4. Have a Child-Pugh class A liver score within 7 days of first dose of study drug; 5. Have a predicted life expectancy of >3 months; 6. Have at least one measurable lesion based on RECIST 1.1 as confirmed by the blinded central imaging vendor; 7. Have a performance status of 0 or 1 using the ECOG Performance Scale within 7 days of first dose of study drug. 8. HbsAg positive. Untreated HBV infected subjects with high copies of HBV DNA are allowed, but anti-Hepatitis B therapy should be initiated immediately on the day of signing informed consent; 9. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving TACE; 10. Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study, starting with the first dose of study medication through at least 120 days or longer based on local regulation after the last dose of study medication; 11. Demonstrate adequate organ function as defined below: (1) Hematological test: Absolute neutrophil count >=1.2x10^9/L, platelets >=60x10^9/L, hemoglobin >=80 g/L without transfusion or EPO dependency within 7 days; (2) Renal function: Serum creatinine =60 ml/min, urine protein =2+, 24 hr urine protein should =30 g/L; (4) Coagulation: International normalized ratio (INR) <=1.5 ULN; 12. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP 150/90 mmHg at baseline screening.
Exclusion criteria
Exclusion criteria: 1. Imaging findings for HCC corresponding to any of the following: HCC with >=50% liver occupation, portal vein invasion with Vp4; 2. Prior local or systemic treatment of hepatocellular carcinoma, including resection, TACE, ablation, targeting and immune therapy; 3. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of Lenvatinib; 4. New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months; 5. Prolongation of QTc (Fridericia formula) interval to >480 ms; 6. Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug; 7. Bleeding or thrombotic disorders (including cerebrovascular accident) or use of factor X inhibitors or anticoagulants requiring therapeutic INR monitoring, eg, warfarin or similar agents. Treatment with low molecular weight heparin is permitted. Antiplatelet agents are prohibited throughout the study; 8. Gastric or esophageal varices that require interventional treatment within 28 days prior to first dose of study drug are excluded. Prophylaxis with pharmacologic therapy (eg, nonselective beta-blocker) is permitted; 9. Active malignancy (except for HCC or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 36 months; 10. Has dual active HBV infection (HBsAg (+) and /or detectable HBV DNA) and HCV infection (anti-HCV Ab(+) and detectable HCV RNA) at study entry; 11. Subjects with CNS metastases are not eligible; 12. Subject is known to be positive for Human Immunodeficiency Virus (HIV); 13. History of clinically significant hepatic encephalopathy; 14. Serious nonhealing wound, ulcer, or bone fracture; 15. History of solid organ or hematologic transplant; 16. Any subject who cannot be evaluated by either triphasic liver computed tomography (CT) or triphasic liver magnetic resonance imaging (MRI) because of allergy or other contraindication to both CT and MRI contrast agents 17. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial; 18. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids (up to 7.5 mg/d of prednisone or equivalent) is allowed; 19. Active infection (any infection requiring systemic treatment); 20. Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs); 21. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis, or has a history of interstitial lung disease; 22. Has received a live-virus vaccination within 30 days of planned treatment start; 23. Has severe hypersensitivity (>=Grade 3) to the study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective response rate;duration of response;Progression-free survival (PFS); | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to progression (TTP);Time to response (TTR);Overall survival (OS);Disease control rate;conversion rate; | — |
Countries
China
Contacts
Public ContactHaibin Zhang
Fifth department of Liver Surgery, Shanghai Eastern Hepatobiliary Hospital
Outcome results
None listed