Systemic Chemotherapy Plus Lenvatinib and Toripalimab for HCC With Extrahepatic Metastasis

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

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

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: Systemic chemotherapy; Drug: Lenvatinib; Drug: Toripalimab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ming Shi, MD; Phone Number: +862087343938; Email: shiming@sysucc.org.cn
• Study Contact Backup: Name: QiJiong Li, MD; Phone Number: +862087343938; Email: liqj@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer Center Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Systemic chemotherapy plus lenvatinib and toripalimab; 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; administration of oxaliplatin , fluorouracil, and leucovorin via the peripherally inserted central catheter every 3 weeks; Drug: Lenvatinib; 12 mg (or 8 mg) once daily (QD) oral dosing.; Drug: Toripalimab; 240mg intravenously every 3 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2019
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (Actual): November 20, 2019

Study Record Updates

• Last Update Posted (Actual): February 23, 2021
• Last Update Submitted That Met QC Criteria: February 19, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Lenvatinib; Toripalimab; Systemic chemotherapy; Oxaliplatin, leucovorin, 5-fluorouracil; Extrahepatic metastasis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Neoplastic Processes; Carcinoma; Carcinoma, Hepatocellular; Neoplasm Metastasis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: HCC-S068

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No