Anlotinib, Hepatocellular Carcinoma, PDL-1, Thermal Ablation
Conditions
Brief summary
In this study, investigators aimed to evaluated the efficacy and safety of microwave ablation combined with anlotinib and TQB2450 Solution in patients with advanced hepatocellular carcinoma. Patients were randomly assigned at a one-to-one ratio to receive microwave ablation plus anlotinib and TQB2450 Solution or microwave ablation plus TQB2450 Solution. Primary end points were objective response rate(ORR). Second end points include overall survival, progression-free survival and disease control rate. Safety was assessed in all patients.
Interventions
DRUGAnlotinib and TQB2450 solution
Anlotinib is a novel multitarget tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling. TQB2450 solution is a new novel of PD-L1 inhibitor made by Crown Bioscience and CHIATAI TIANQING(CTTQ PHARMA).
DRUGTQB2450 solution
TQB2450 solution is a new novel of PD-L1 inhibitor made by Crown Bioscience and CHIATAI TIANQING(CTTQ PHARMA).
Sponsors
Chinese PLA General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. ECOG PS score: 0-1, Life expectancy of 3 months or more 2. Subjects must have confirmed diagnosis of HCC 3. BCLC B and C grade 4. At least 1 measurable target lesion according to mRECIST 5. Child-Pugh score A to B 6. No locoregional therapy within 4 weeks before enrollment for patients with unresectable HCC or tumor progression after locoregional therapy; All toxicities related to prior treatments must be resolved to Grade ≤1 7. No prior treatment with anti-angiogenic drugs or any anti-PD-1 agent within 4 weeks before enrollment 8. HBV DNA\<500IU/mL 9. Adequate organ function within 14 days before enrollment 10. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to the start of study drug. Women must not be breastfeeding. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment 11. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol
Exclusion criteria
1. Prior liver transplant 2. Any prior (within 1 year) or current clinically significant ascites as measured by physical examination and that requires active paracentesis for control 3. Prior treatment with an anti-PD-L1 4. Active autoimmune disease that has required systemic treatment in past 2 years 5. Known or suspected allergy to Anlotinib and TQB2450 Solution or study drug components；History of severe hypersensitivity reaction to any monoclonal antibody 6. Has received a live-virus vaccination within 30 days of planned treatment start. 7. Subjects with CNS metastases are not eligible, unless they have completed local therapy (eg, whole brain radiation therapy \[WBRT\], surgery or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (eg, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment 8. Subjects with any active, known, or suspected autoimmune disease； Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) 9. HBV DNA ≥ 1000 IU/ml，HCV RNA 10. 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, Prolongation of QTc (Fridericia formula) interval to \>480 ms 11. Dysfunction of blood coagulation （INR\>1.5 or APTT\>1.5×ULN）, Bleeding or thrombotic disorders 12. Anticoagulants requiring therapeutic INR monitoring, eg, warfarin or similar agents. Antiplatelet agents and low molecular weight heparin are prohibited throughout the study 13. Active infection (any infection requiring systemic treatment) 14. History of solid organ or hematologic transplant 15. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 2-year | Objective Response Rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | 2-year | Progression-free Survival |
| DCR | 2-year | Disease Control Rate |
| EORTC QLQ C30 | Change from baseline health related quality of life at 2 years | Impact of treatment on Health Related Quality of Life (HRQoL) for subjects treated using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. EORTC QLQ C30 scales were grouped and converted to score 0 to 100 according to the scoring manual; a higher score represents a more severe symptom or problem. |
| OS | 2-year | Overall Survival |
| AE | 2-year | Incidence of Adverse Events |
| SAEs | 2-year | Incidence of Severe Adverse Events |
| EORTC QLQ-HCC18 | Change from baseline health related quality of life at 2 years | Impact of treatment on Health Related Quality of Life (HRQoL) for subjects treated using HCC-specific EORTC QLQ-HCC18 questionnaire. EORTC QLQ-HCC18 scales were grouped and converted to score 0 to 100 according to the scoring manual; a higher score represents a more severe symptom or problem. |
Countries
China
Contacts
Primary ContactPing Liang
Outcome results
None listed