TACE Combinated With Sorafenib in Treating Patients With Unresectable Hepatocellular Carcinoma

Phase II Trail of TACE Combinated With Sorafenib in Treating Patients With Unresectable Hepatocellular Carcinoma

TACE is widely used in patients with unresectable HCC. However, it is a non-curative approach; thus ,strategies to further improve the survival of these patients are needed. Sorafenib is regarded as standard treatment for advanced HCC. It is the first systemic therapy to demonstrate a significant survival benefit in HCC patients.The hypothesis is that the combination of TACE with sorafenib could improve the survival of patients with unresectable HCC.

Study Overview

• Status: Unknown
• Conditions: Carcinoma, Hepatocellular; PHENYTOIN/SORAFENIB [VA Drug Interaction]
• Intervention / Treatment: Procedure: TACE; Drug: sorafenib combined with TACE

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital and Institute
    • Jinan, Shandong, China, 250021
      • Shandong Medical Imaging Research Institute
    • Jinan, Shandong, China, 250114
      • Qilu Hospital of Shandong University
    • Qingdao, Shandong, China, 266003
      • The Affiliated Hospital of Medical College Qingdao University
    • Yantai, Shandong, China, 264000
      • Yantai Yuhuangding 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:

• Patients newly diagnosed as HCC according to European Association for Study of the Liver criteria.
• BCLC stage B or C
• Child-Pugh class score≤8
• ECOG performance status ≤2
• Etiology: Hepatitis B virus(HBV) infection
• Written informed consent (approved by the Institutional Review Board [IRB]obtained prior to any study specific screening procedures
• Patient must be able to comply with the protocol
• Age 18-75 years
• Haematology:Absolute neutrophil count (ANC) > 1.5 x 109/L, Platelet count > 50 x 109/L, Haemoglobin > 9 g/dL (may be transfused to maintain or exceed this level) Prothrombin time international normalized ratio < 1.5
• Biochemistry:Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)< 5 x the upper limit of normal,Total bilirubin < 3 x the upper limit of normal,Serum creatinine < 1.5 x the upper limit of normal,Cholinesterase>0.5x the lower limit of normal，Prealbumin>0.5x the lower limit of normal.
• Life expectancy of > 3 months

Exclusion Criteria:

• BCLC stage D
• Child-Pugh Score≥9
• Clinically severe gastrointestinal bleeding within 4 weeks of the start of treatment
• Preexisting or history of hepatic encephalopathy
• uncontrolled hypertension
• Pregnancy (positive serum pregnancy test) or lactation
• Serious, non-healing wound, ulcer, or bone fracture
• Currently or recent (within the 30 days prior to starting study treatment) treatment of another investigational drug or participation in another investigational study
• Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents ( ≤ 6 months prior to study entry), myocardial infarction ( ≤ 6 months prior to study entry), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
• Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of Sorafenib/TACE or patient at high risk from treatment complications
• Other severe concomitant disease that may reduce life expectancy
• Risk of allergic reactions to the study drugs
• Drug abuse or other physical, psychological , or social problems that may interfere with the participation in the study or evaluation of study results

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group TACE; TACE will be carried out with chemotherapeutic agents and lipiodol; additional embolisation will be carried out with gelatin sponge particles. TACE will be repeated if clinically indicated	Procedure: TACE; After obtaining arterial access,a diagnostic visceral arteriogram will be performed to demonstrate arterial supply to the tumor and the presence of variant arterial anatomy.After having positioned the catheter within the artery feeding tumor,the chemoembolization mixture will be infused into th e artery until stagnant flow is observed.
Experimental: Group Combination; All patients will receive Sorafenib (800 mg/day) p.o. beginning four weeks after the first TACE and every day thereafter until patient death or premature withdrawal from study	Drug: sorafenib combined with TACE; All patients will receive Sorafenib (800 mg/day) p.o. beginning four weeks after the first TACE and every day thereafter until patient death or premature withdrawal from study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression	Time to progression is defined as time from randomization to radiological progression and will be evaluated every 8 week	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FACT-Hep	FACT-Hep is a chart established to evaluate the life quality of patients with HCC every 4 weeks	six months
Disease control rate	CR+PR+SD	six months after TACE
Safety	Number of participants with adverse events as a measure of safety and tolerability(According to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0)	six months
PFS and OS	The overall survival is defined as time from randomization to death due to any cause, and will be evaluated every 8 weeks in the protocol treatment, and every one year in the follow-up period,respectively	two years
Number of TACE sessions and the interval time between two TACE sessions		2 years
AFP		six months

Collaborators and Investigators

• Sponsor: Shandong Cancer Hospital and Institute
• Investigators: Principal Investigator: Jinlong Song, MD, Shandong Cancer Hospital and Institute

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Anticipated): December 1, 2013
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: May 11, 2012
• First Submitted That Met QC Criteria: May 21, 2012
• First Posted (Estimate): May 25, 2012

Study Record Updates

• Last Update Posted (Estimate): May 25, 2012
• Last Update Submitted That Met QC Criteria: May 21, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; sorafenib; transarterial chemoembolization
• 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; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Estrogens, Non-Steroidal; Estrogens; Protein Kinase Inhibitors; Chlorotrianisene; Sorafenib
• Other Study ID Numbers: ShandongCHI-002