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Lenvatinib is an oral multi-target receptor tyrosine kinase inhibitor (TKI) inhibitor that mainly inhibits the Endothelial growth factor receptor (VEGFR) VEGFR-1,2,3; Fibroblast growth factor receptor, FGFR) FGFR-1,2,3,4; Platelet-derived growth factor receptor (PDGFR) PDGFRα; The kinases RET and KIT, thereby inhibiting tumor cell proliferation, inducing apoptosis, and playing an anti-angiogenic role, have been approved by the FDA and CFDA as first-line treatment for patients with advanced liver cancer. lenvatinib showed longer disease progression than sorafenib (8.9 months vs. sorafenib. 3.7 months), longer progression-free survival (7.4 months vs. 3.7 months), and higher disease control rates (24.1% vs. 9.2%). Therefore, lenvatinib has obvious advantages in HCC treatment because of its strong anti-angiogenic and anti-tumor growth effects.
Cindilimab is a human immunoglobulin G4 (IgG4) monoclonal antibody that specifically binds to PD-1 molecules on the surface of T cells, thereby blocking the programmed death receptor-1 (PD-1)/programmed death receptor-1 ligand (PD-L1) pathway induced by tumor immune tolerance, and reactivating the antitumor activity of lymphocytes.
In summary, recurrence after radical treatment of liver cancer is an urgent clinical problem. Recurrent HCC treatment represented by resection, ablation and TACE is difficult to achieve more satisfactory efficacy. The main ablative techniques includes radiofrequency ablation, microwave ablation and cryoablation.As a local treatment for liver cancer, ablation has the risk of incomplete ablation and insufficient ablation margin, and because RFA cannot resolve micrometastases, tumor growth, invasion and metastasis occur. Therefore, ablation combined with lenvatinib and immune checkpoint inhibitors have theoretical complementary advantages, and this study intends to compare the clinical efficacy and safety of ablation combined with lenvatinib plus anti-PD-1 antibodies in the treatment of patients with early recurrent liver cancer compared with ablation alone.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ablation + Lenvatinib +anti-PD-1 Antibodies | Experimental | Experimental: ablation + lenvatinib +anti-PD-1 antibodies ablation: ultrasound-guided percutaneous ablation for recurrent hepatocellular carcinoma. After local anesthesia and intravenous sedation, the unipolar needle was gradually inserted into the lesion and placed at the deepest edge of the lesion. Ablation electrodes are unipolar needles with bare ends of 2 or 3cm (depending on tumor size). Lenvatinib: (TBILI<2 times the upper limit of normal) about 3 to 7 days after treatment. The dosage and usage of the regimen were 8mg qd po (body weight < 60kg) or 12mg qd po (body weight ≥60kg). Anti-PD-1 Antibodies: About 3 to 7 days after radiofrequency ablation, (TBILI<2 times the upper limit of normal). The dosage was used accordingt to the drug instructions., every 3 weeks for a course of treatment. The longest course of treatment is 6 months. |
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| Ablation | Active Comparator | Experimental group: ablation Ablation: ultrasound-guided percutaneous ablation for recurrent hepatocellular carcinoma. After local anesthesia and intravenous sedation, the unipolar needle was gradually inserted into the lesion and placed at the deepest edge of the lesion. Ablation electrodes are unipolar needles with bare ends of 2 or 3cm (depending on tumor size). The ablation power is 150W (range from 100 to 200W). In general, the average ablation time per lesion is about 12 minutes (ranging from 10 to 15 minutes). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| lenvatinib + anti-PD-1 antibodies | Drug | A ablation treatment group B ablation+ lenvatinib + anti-PD-1 antibodies treatment group |
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| Measure | Description | Time Frame |
|---|---|---|
| Recurrence-free Survival, RFS | Defined as the percentage of patients who had achieved 1 year of disease recurrence (i.e., intrahepatic recurrence or extrahepatic metastasis) or death (from any cause) from the date of enrollment, whichever occurred first. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Recurrence free survival (RFS) at 2 years | Defined as the percentage of patients with no disease recurrence (i.e., intrahepatic recurrence or extrahepatic metastasis) or death (from any cause) for 2 years from the date of enrollment. | 2 years |
| Recurrence free survival (RFS) at 3 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hua Li | Contact | 13060975202 | lihua100@yeah.net |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Third Affiliated Hospital, Sun Yat-Sen University | Recruiting | Guangzhou | Guangdong | 510000 | China |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C531958 | lenvatinib |
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| ablation | Procedure | radiofrequency ablation or microwave ablation |
|
Defined as the percentage of patients with no disease recurrence (i.e., intrahepatic recurrence or extrahepatic metastasis) or death (from any cause) for 3 years from the date of enrollment. |
| 3 years |
| Safety: Incidence of adverse events | Incidence of adverse events, severe AES, death, and laboratory abnormalities in treated patients. | 18 months |
| Overall Survival (OS) | Overall Survival (OS): defined as the time from randomization to death from any cause throughout the trial. Patients who drop out or are lost to follow-up will be treated as deleted, with the last known date of survival as the last time of survival. Patients still alive at the end of the study will also be treated as deleted, with the last known date of survival as the last survival time. | 18 months |
| Recurrence free Survival (RFS) | Recurrence free Survival (RFS): defined as the time between recurrence of tumor or death (from any cause) after recurrence of HCC. | 18 months |
| Biomarkers in tumors and peripheral blood | Biomarkers in tumor and peripheral blood such as AFP, CEA, CA199, CA125, RBC, Alb | 18 months |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |