HAIC Combined With Lenvatinib and Sintilimab for Hepatocellular Carcinoma With PVTT

HAIC Combined With Lenvatinib and Sintilimab for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

This study intends to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus lenvatinib and Sintilimab for patients hepatocellular carcinoma and portal vein tumor thrombus.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Hepatocellular; Liver Neoplasms; Sintilimab; Portal Vein Tumor Thrombus
• Intervention / Treatment: Drug: Lenvatinib; Procedure: Hepatic arterial infusion chemotherapy; Drug: Sintilimab

Detailed Description

Hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, 5-fluorouracil and leucovorin was effective and safe for hepatocellular carcinoma. Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma, and Sintilimab, an programmed cell death protein-1 (PD-1) antibody, was effective and tolerable in patients with hepatocellular carcinoma and portal vein tumor thrombus. No study has evaluated HAIC plus Lenvatinib and Sintilimab. Thus, the investigators carried out this prospective, single-arm study to find out it.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Second Affiliated Hospital of Guangzhou Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. clinical diagnosis of HCC; 2. age between18 and 75 years; 3. refused to sorafenib treatment; 4. type I PVTT, type II PVTT, or type III PVTT. 5. Child-Pugh class A or B; 6. Eastern Cooperative Group performance status (ECOG) score of 0-2; 7. Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/L Serum albumin ≥ 32 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 8. Prothrombin time ≤18s or international normalized ratio < 1.7. 9. Ability to understand the protocol and to agree to and sign a written informed consent document.

Exclusion Criteria:

• 1. Diffuse HCC; 2. Extrahepatic metastasis; 3. Obstructive PVTT involving both the left and right portal vein or main portal vein.

  4. Serious medical comorbidities. 5. Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy 6. Known history of HIV 7. History of organ allograft 8. Known or suspected allergy to the investigational agents or any agent given in association with this trial.

  9. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy 10. Evidence of bleeding diathesis. 11. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.

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: HAIC plus Lenvatinib and Sintilimab; Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 6 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Toripalimab 200 mg intravenously every 3 weeks.	Drug: Lenvatinib; 12 mg (or 8 mg) once daily (QD) oral dosing.; Other Names: TKI inhibits; Procedure: Hepatic arterial infusion chemotherapy; administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 6 weeks; Drug: Sintilimab; 200mg intravenously every 3weeks; Other Names: programmed cell death protein-1 (PD-1) antibody

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
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
Objective response rate (ORR)	ORR, as determined based on tumor response according to RECIST 1.1, is defined as the proportion of all randomized subjects whose best overall response (BOR) is either a CR or PR.	6 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Second Affiliated Hospital of Guangzhou Medical University
• Investigators: Study Director: Kangshun Zhu, MD, Second Affiliated Hospital of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): December 30, 2022

Study Registration Dates

• First Submitted: October 31, 2020
• First Submitted That Met QC Criteria: October 31, 2020
• First Posted (Actual): November 5, 2020

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: oxaliplatin; leucovorin; Carcinoma, Hepatocellular; Sintilimab; lenvatinib; 5-fluorouracil; portal vein tumor thrombus
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Embolism and Thrombosis; Carcinoma; Carcinoma, Hepatocellular; Thrombosis; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: GYEYJR-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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