HAIC Plus Lenvatinib and PD-1 Antibody Versus HAIC Plus Lenvatinib for Advanced HCC

Hepatic Arterial Infusion Chemotherapy Plus Lenvatinib and Programmed Cell Death Protein-1 Antibody Versus Hepatic Arterial Infusion Chemotherapy Plus Lenvatinib for Advanced Hepatocellular Carcinoma

The purpose of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus lenvatinib and programmed cell death protein-1 antibody compared with lenvtinib Alone in patients with hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus lenvatinib for advanced hepatocellular carcinoma (HCC)

Study Overview

• Status: Withdrawn
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Lenvatinib; Drug: PD-1 antibody; Drug: Folfox Protocol; Procedure: Hepatic arterial infusion chemotherapy

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 programmed cell death protein-1 (PD-1) antibody was effective and tolerable in patients with advanced hepatocellular carcinoma. No study has compared HAIC plus lenvatinib and PD-1 antibody with HAIC plus lenvatinib. Thus, the investigators carried out this prospective randomized control study to find out it.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Cancer Center Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510620
      • Guangzhou Twelfth People 's Hospita
    • Kaiping, Guangdong, China, 529300
      • Kaiping Central Hospital

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
• 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

• Ability to understand the protocol and to agree to and sign a written informed consent document

Exclusion Criteria:

• Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
• Known history of HIV
• History of organ allograft
• 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HAIC plus lenvatinib and PD-1 antibody; Hepatic arterial infusion chemotherapy plus lenvatinib and programmed cell death protein-1 antibody	Drug: Lenvatinib; 12 mg (or 8 mg) once daily (QD) oral dosing.; Drug: PD-1 antibody; 3mg/kg intravenously every 2 weeks; Drug: Folfox Protocol; Oxaliplatin , fluorouracil, and leucovorin; Procedure: Hepatic arterial infusion chemotherapy; administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries
Active Comparator: HAIC plus lenvatinib; Hepatic arterial infusion chemotherapy plus lenvatinib	Drug: Lenvatinib; 12 mg (or 8 mg) once daily (QD) oral dosing.; Drug: Folfox Protocol; Oxaliplatin , fluorouracil, and leucovorin; Procedure: Hepatic arterial infusion chemotherapy; administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), or date of death, whichever occurred first.	12 months
Objective Response Rate (ORR)	ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on mRECIST. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference to the baseline sum of the diameters of target lesions.	12 months
Adverse Events	Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03	12 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Guangzhou No.12 People's Hospital; Kaiping Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2019
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: January 11, 2019
• First Submitted That Met QC Criteria: January 11, 2019
• First Posted (Actual): January 14, 2019

Study Record Updates

• Last Update Posted (Actual): May 6, 2019
• Last Update Submitted That Met QC Criteria: May 2, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Hepatic arterial infusion chemotherapy; Lenvatinib; PD-1 Antibody; Oxaliplatin, 5-Fluorouracil and Leucovorin
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Protein Kinase Inhibitors; Antibodies; Lenvatinib
• Other Study ID Numbers: HCC-S058

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No