TACE Combined With Lenvatinib and MWA in the Treatment of Locally Advanced Large Hepatocellular Carcinoma

Study Overview
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Brief Summary
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To explore the objective effectiveness and safety of TACE combined with Lenvatinib in the treatment of advanced liver cancer. After successful down-stage, radical microwave ablation was further performed.

Detailed Description
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The purpose of this study is to explore the objective effective rate of TACE combined with Lenvatinib in the treatment of locally advanced liver cancer, so as to provide a new idea for the radical microwave ablation treatment mode after the decline of locally advanced liver cancer.

Official Title
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Prospective Single Arm Phase II Study of TACE Combined With Lenvatinib and MWA After Down-stage in the Treatment of Locally Advanced Large Hepatocellular Carcinoma

Conditions
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Liver Tumor

Intervention / Treatment
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* Drug: TACE combined with Lenvatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18-75 years with hepatocellular carcinoma have an expected survival of at least 3 months; Number of tumors ≤ 3; Large hepatocellular carcinoma with tumor diameter ≥ 7 cm; Patients without inferior vena cava tumor thrombus, portal vein tumor thrombus and cholangiocarcinoma thrombus; Although there is arteriovenous fistula or arterioportal fistula, it can be completely blocked; Child Pugh grade A or B of liver function; ECoG physical fitness score < 2; No bleeding tendency, normal coagulation function or coagulation dysfunction can be corrected after treatment; Leukocyte count ≥ 3.0 × 109/L； Hemoglobin ≥ 8.5g/dl; Platelet count ≥ 50 × 109/L； The international normalized ratio of prothrombin time (INR) ≤ 2.3 or prothrombin time (PT) does not exceed the upper limit of normal control for 3 seconds; Serum creatinine was less than 1.5 times of the upper limit of normal; Patients and / or family members agree to join the clinical trial and sign the informed consent form Exclusion Criteria: Diffuse hepatocellular carcinoma; Portal vein tumor thrombus; Combined with tumor thrombus of hepatic vein and inferior vena cava; Patients with lymph node metastasis and extrahepatic distant metastasis; The liver function was classified as child Pugh C and could not be improved by liver protection treatment; Arteriovenous fistula or arterioportal fistula with ineffective intervention; Uncorrectable coagulation dysfunction and obvious hemogram abnormalities, with obvious bleeding tendency; Intractable massive ascites; ECoG physical fitness score > 2 points; Combined with active infection, especially bile duct inflammation; Serious heart, lung, kidney, brain and other important organ diseases; Note: see attached table 1 for child Pugh classification of liver function; See attached table 2 for ECoG physical fitness score

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TACE combined with Lenvatinib<br>Three days after the first TACE treatment, when the liver function was evaluated as grade A / B, Lenvatinib was taken orally, 8mg / day (body weight less than 60kg) or 12mg / day (body weight equal to or more than 60kg). | Drug: TACE combined with Lenvatinib<br>* Three days after the first TACE treatment, when the liver function was evaluated as grade A / B, Lenvatinib was taken orally, 8mg / day (body weight less than 60kg) or 12mg / day (body weight equal to or more than 60kg). Lenvatinib reduction standard: 8mg / day; 4mg / day; 4mg, the next day.<br>* Other names: lenvima;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Down stage rate | if the patient achieve any of these three criteria： ① the patient was downgraded from BCLC stage C to BCLC stage B (portal branch tumor thrombus was inactive, the focus was less than or equal to 7cm; or the focus did not invade the surrounding tissue after shrinking) or Milan standard (single tumor diameter was not more than 5cm or less than or equal to 3 tumors, and the maximum diameter was not more than 3cm, without vascular invasion). ② Liver function reaches child Pugh grade A or B; ③ The patient is in good health and can tolerate ablation. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RFS | Recurrence free survival indicates the length of time after MWA for a cancer ends that the patient survives without any signs or symptoms of HCC | 3 years | 
| Objective response rate | Change of the tumor size according to the modified response evaluation criteria in solid tumors (mRECIST) [see attached table 3], the efficacy is defined as CR (complete remission), PR (partial remission), SD (stable) and PD (Progress) | 3 years | 
| Changes of liver and kidney function | Changes of liver and kidney function index from blood biochemistry compared to baseline | 3 years | 
| TACE frequency and ablation frequency | To access the times and frequency of TACE and ablation | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TACE, Large hepatocellular carcinoma, Lenvatinib, Microwave ablation