Lenvatinib Combined With TACE and Camrelizumab in Conversion Resection for Advanced Hepatocellular Carcinoma (LEN-TAC Study)

Study Overview
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Brief Summary
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Compared with systemic therapy alone, conversion therapy is promising to improve the prognosis of patients with advanced hepatocellular carcinoma (HCC). Triple therapy (lenvatinib combined with transcatheter arterial chemoembolization and camrelizumab) may have significant efficacy in conversion therapy in patients with advanced HCC, but its safety and efficacy are unknown. We designed a randomized, open-label, parallel-controlled trial to investigate the safety and efficacy of lenvatinib combined with transcatheter arterial chemoembolization and camrelizumab versus lenvatinib alone in conversion resection for advanced HCC. Totally 168 patients with BCLC C stage HCC will be rigorously screened and included, and the primary endpoints of the study are 2-year overall survival and conversion resection rate. This study will serve as a reference for new treatment strategies for advanced HCC.

Official Title
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Lenvatinib Combined With Transcatheter Arterial Chemoembolization and Camrelizumab Versus Lenvatinib Alone in Conversion Resection for Advanced Hepatocellular Carcinoma:A Randomized, Open-label, Parallel-controlled, Phase III Study(LEN-TAC Study)

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Combination Product: Lenvatinib combined with TACE and Camrelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria (1)18 to 75 years of age; (2)Patients with HCC who strictly meet the criteria of Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition) or are diagnosed by histopathology or cytology; (3)No prior anticancer therapy for HCC; (4)ECOG PS score 0-1; (5)Child-Pugh class A   B; (6)BCLC stage C Patients: tumor localized in one half of liver with portal vein tumor thrombus (according to PVTT typing, Vp1   Vp4 patients without contralateral portal vein tumor thrombus); (7)At least one radiographically measurable lesion according to mRECIST; (8)In HBsAg-positive patients, HBV-DNA<2000 IU/ml (10^4 copies/ml) when PD-1 monoclonal antibody treatment is performed; HCV RNA is negative when HCV antibody is positive; (9)Adequate organ function defined by laboratory test results; (10)Adequate blood pressure (BP) control with up to 3 antihypertensive agents, defined as BP≤150/90 mmHg at screening and no change in antihypertensive therapy within 1 week prior to Cycle 1/Day 1. (11)Patients expected to survive more than 3 months. (12)No plans to be pregnant. Exclusion criteria Known intrahepatic cholangiocarcinoma, sarcomatoid HCC, mixed hepatocellular carcinoma, and fibrolamellar cell carcinoma; Extrahepatic metastasis of HCC; Diffuse HCC or intrahepatic tumor burden ≥ 50% (including tumor contralateral portal vein tumor thrombus, superior mesenteric vein tumor thrombus, and inferior vena cava tumor thrombus); Contraindications to TACE or epirubicin; Known hypersensitivity to lenvatinib ingredients; Known hypersensitivity to the active ingredient or excipients of Camrelizumab; With other malignancies; Pregnant or lactating women, or fertile patients who are unwilling or unable to take effective contraceptive measures; Patients with class II or higher myocardial ischemia or myocardial infarction, or poorly controlled arrhythmia (including QTc interval ≥ 470 ms); according to NYHA classification for chronic heart failure, cardiac insufficiency class III-IV, or left ventricular ejection fraction (LVEF) < 50% by echocardiography; Abnormal coagulation function [INR > 1.5 or PT > upper limit of normal (ULN) + 4 seconds or APTT > 1.5 ULN], bleeding tendency or receiving thrombolytic or anticoagulant therapy; History of psychiatric disorders or psychotropic substance abuse; Combined with HIV infected; Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; Patients with active infection; Patients with poor compliance such as floating population; Prior treatment with any of the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 agents, or drugs targeting other T-cell co-stimulatory receptors or co-inhibitory receptors. Active autoimmune disease requiring systemic therapy within 2 years prior to the first dose (the alternative therapy is not considered systemic); Receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose, except for physiological doses of glucocorticoids (≤ 10 mg/day prednisone or equivalent); Presence of clinically uncontrolled pleural/peritoneal effusion (patients who do not require drainage of fluid and who stop receiving drainage for 3 days without significant increase in volume can be included); Acute or chronic active chronic active hepatitis B or C with HBV-DNA ≥ 200,000 IU/ml (or 10^6 copies/ml) or HCV RNA ≥ 10^3 copies/ml when treated with PD-1 monoclonal antibody; Vaccination with live vaccines within 30 days prior to first dose (Cycle 1/Day 1). Inactivated viral vaccines against seasonal influenza within 30 days prior to first dose are permitted, but live attenuated intranasal influenza vaccines are not permitted.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lenvatinib combined with TACE and camrelizumab<br> | Combination Product: Lenvatinib combined with TACE and Camrelizumab<br>* After all subjects sign informed consent and pass screening, they are randomized in a 1:1 ratio to either the experimental arm (lenvatinib combined with TACE and camrelizumab) or the control arm (lenvatinib alone), and randomization is stratified according to the number of tumors (single versus multiple) and portal vein tumor thrombus (Vp1   3 vs. Vp4). Eight sites in China will be included in this study with follow-up of 2 years.<br>|
| Active Comparator: lenvatinib alone<br> | Combination Product: Lenvatinib combined with TACE and Camrelizumab<br>* After all subjects sign informed consent and pass screening, they are randomized in a 1:1 ratio to either the experimental arm (lenvatinib combined with TACE and camrelizumab) or the control arm (lenvatinib alone), and randomization is stratified according to the number of tumors (single versus multiple) and portal vein tumor thrombus (Vp1   3 vs. Vp4). Eight sites in China will be included in this study with follow-up of 2 years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conversional resection rate | conversional resection patients/enrolled patients | 2 years | 
| Overall survival at 2 years | The time from start of treatment until death from any cause or the end of the study (the last enrolled patient should be followed for at least 2 years | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | The occurrence of any hematological or non-hematological toxicity event (≥ class Ⅲ), including but not limited to impaired liver function, impaired hematological system, hypertension, diarrhea, proteinuria, hand-foot syndrome, etc. Severity of adverse events will be graded according to CTCAE v5.0. | 2 years | 
| Objective response rate | The percentage of patients achieving complete response and partial response among all patients. Response to treatment will be evaluated according to mRECIST. | 2 years | 
| Disease control rate | The percentage of patients with complete response, partial response and stable disease among all patients. | 2 years | 
| Event-free survival | Time from randomization to disease progression, local recurrence, distant metastasis, or death, whichever occurs first, assessed by mRECIST | 2 years | 
| Quality of life assessment | Standardized scoring according to QLQ-C30 V3.0 of the EORTC. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Conversion resection, Lenvatinib, Transcatheter arterial chemoembolization, Camrelizumab, Advanced hepatocellular carcinoma