Systemic Chemotherapy Plus Lenvatinib and Toripalimab for HCC With Extrahepatic Metastasis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of Systemic chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus lenvatinib and toripalimab in patients with hepatocellular carcinoma with extrahepatic metastasis

Detailed Description
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Systemic chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin was effective and safe for advanced hepatocellular carcinoma. Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma, and programmed cell death protein-1 (PD-1) antibody was effective and tolerable in patients with advanced hepatocellular carcinoma. No study has evaluated systemic chemotherapyplus lenvatinib and toripalimab. Thus, the investigators carried out this prospective, single-arm study to find out it.

Official Title
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Systemic Chemotherapy of Oxaliplatin, Leucovorin, 5-fluorouracil Plus Lenvatinib and Toripalimab for Hepatocellular Carcinoma With Extrahepatic Metastasis: a Prospective, Single-arm Trial

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: Systemic chemotherapy
* Drug: Lenvatinib
* Drug: Toripalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL) Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria. Barcelona clinic liver cancer-stage C Eastern Cooperative Oncology Group performance status of 0 to 2 With no previous treatment Presence of extrahepatic metastasis No Cirrhosis or cirrhotic status of Child-Pugh class A only Not amendable to surgical resection ,local ablative therapy and any other cured treatment. The following laboratory parameters: Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/L Serum albumin ≥ 30 g/L ASL and AST ≤ 5 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) >1,500/mm3 Exclusion Criteria: Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy Known history of HIV History of organ allograft History of immunotherapy Known or suspected allergy to the investigational agents or any agent given in association with this trial. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy Evidence of bleeding diathesis. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry. Known central nervous system tumors including metastatic brain disease

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: Systemic chemotherapy plus lenvatinib and toripalimab<br>Systemic chemotherapy of oxaliplatin , fluorouracil, and leucovorin every 3 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Toripalimab 240mg intravenously every 3 weeks. | Procedure: Systemic chemotherapy<br>* administration of oxaliplatin , fluorouracil, and leucovorin via the peripherally inserted central catheter every 3 weeks<br>Drug: Lenvatinib<br>* 12 mg (or 8 mg) once daily (QD) oral dosing.<br>Drug: Toripalimab<br>* 240mg intravenously every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival rate at 6 months | Progression was defined as progressive disease by independent radiologic review according to mRECIST or death from any cause | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS is the length of time from the date of randomization until death from any cause. | 6 months | 
| Progression free survival (PFS) | PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression or death due to any cause. | 6 months | 
| Objective response rate (ORR) | ORR, as determined based on tumor response according to mRECIST, is defined as the proportion of all randomized subjects whose best overall response (BOR) is either a CR or PR. | 6 months | 
| Adverse events | Safety will be evaluated according to the NCI CTCAE Version 4.03. All observations pertinent to the safety of the study medication will be recorded on the CRF and included in the final report. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Lenvatinib, Toripalimab, Systemic chemotherapy, Oxaliplatin, leucovorin, 5-fluorouracil, Extrahepatic metastasis