Efficacy and Safety of Donafenib in Patients With Advanced Hepatocellular Carcinoma

Efficacy and Safety of Donafenib in Patients With Advanced Hepatocellular Carcinoma: a Controlled,Multicentre,Randomised, Phase 3 Trial

Donafenib versus sorafenib for advanced hepatocellular cancer.

Study Overview

• Status: Completed
• Conditions: HCC
• Intervention / Treatment: Drug: Donafenib; Drug: Sorafenib

Detailed Description

This phase 3 study of donafenib, an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases, is to assess efficacy and safety in patients wiht advanced hepatocellular carcinoma (HCC).The study is a randomised,controlled,multicentre study.The controlled drug is sorafenib(Nexavar).The primary endpoint is overall survival.

• Study Type: Interventional
• Enrollment (Actual): 668
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 025
      • The PLA 81 Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610042
      • West China Hospital Sichuan University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Above 18 years old;
• Patients with measurable, histologically or clinical proven, inoperable HCC;
• Patients wtih measurable lesion and proved by independent radiology committee(IRC);
• Child-Pugh (CP) score of 7 or less；
• Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less;
• Patients had not received prior systemic treatments for HCC;
• Life expectancy at least 3 months;
• Adequate hepatic and renal function;
• Adequate hematologic function (platelet count,≥75×109per liter;hemoglobin ≥9.0g per deciliter;neutrophil≥1.5×109per liter,);
• Prothrombin time international normal.

Exclusion Criteria:

• Patients received operate in 3 months;
• Patients received transcatheter arterial chemoembolization（TACE） in 4 weeks;
• Patients had received systemic therapy;
• Patients had prior treatment with sorafenib;
• Central nervous system(CNS) involvement;
• Severe or mild-degree ascitic fluid;
• Main portal vein tumor thrombus;
• Inferior venae cava tumor thrombus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Donafenib; Drug:Donafenib; Dose:200mg,bid,po.	Drug: Donafenib; Donafenib is an oral multikinase inhibitor with antiproliferative and antiangiogenic effects; Other Names: CM4307
Active Comparator: Sorafenib(Nexavar); Drug:Sorafenib; Dose:400mg,bid,po.	Drug: Sorafenib; Control; Other Names: Nexavar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Patient visits are scheduled every 8 weeks to monitor efficacy.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progress Free Survival	Patient visits are scheduled every 8 weeks to monitor efficacy.Progressive disease is measured from the date of randomization until dead or disease progression according to Response Evaluation Criteria in Solid Tumors(Version 1.1)	2 years
Percentage of adverse events	Patient visits are scheduled every 4 weeks to monitor safety and drug accountability. Patients were monitored for adverse events by use of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) version 4.0	3 years

Collaborators and Investigators

• Sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
• Collaborators: Tigermed Consulting Co., Ltd
• Investigators: Study Chair: Shukui Qin, MD, The PLA 81 Hospital; Study Chair: Feng Bi, MD, West China hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): November 27, 2019
• Study Completion (Actual): December 17, 2019

Study Registration Dates

• First Submitted: December 31, 2015
• First Submitted That Met QC Criteria: January 4, 2016
• First Posted (Estimate): January 5, 2016

Study Record Updates

• Last Update Posted (Actual): January 9, 2020
• Last Update Submitted That Met QC Criteria: January 7, 2020
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Sorafenib; Phase 3; Overall Survival; Donafeinb
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: ZGDH3

Plan for Individual participant data (IPD)

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