Sorafenib VS TACE in HCC Patients With Portal Vein Invasion

An Open Label, Phase 2 Trial Comparing Sorafenib And TACE in Advanced Hepatocellular Carcinoma With Portal Vein Invasion

The investigators are going to compare the therapeutic effect of sorafenib and transarterial chemoembolization in advanced hepatocellular carcinoma with major branch of portal vein invasion.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Sorafenib; Procedure: TACE for HCC with portal vein invasion

Detailed Description

TACE is an established therapy for patients with unresectable hepatocellular carcinoma (HCC) and has been shown to significantly improve survival in these patients compared to no treatment. Moreover, TACE can be performed safely and may improve the overall survival of patients with HCC and major branch of portal vein invasion. Sorafenib, already approved for HCC, could lead to significantly improvement in tumor control and survival in patients with advanced stage HCC. So far there are no head to head comparison reports about the efficacy of Sorafenib and TACE. Here the investigators evaluate the efficacy of sorafenib and TACE in advanced HCC with major branch of portal vein invasion.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 80 > Age >= 18 years.
2. Child-Pugh class A (class B could be included when Childs score is 7).

3. Hepatocellular carcinoma with major branch of portal vein invasion on dynamic CT or MRI

   • not only newly diagnosed treatment-naive patients,
   • but also HCC patients previously treated with other therapies in case of development of major branch of portal vein invasion

4. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements:

   • White blood cell counts (WBC) >= 2,000 /μl, Absolute neutrophil count (ANC) > 1,200/μl
   • Hemoglobin >= 8.0 g/dl
   • Platelet count > 50,000/μl
   • Serum creatinine < 1.7 mg/dl
   • Total bilirubin =< 3.0 mg/dl
   • Prothrombin Time (PT)-international normalized ratio (INR) =< 2.3 or Prothrombin Time (PT)-sec =< 6 sec
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

Exclusion Criteria:

1. Child-Pugh score >= 8.
2. Age < 18 or >= 80 years.
3. ECOG Performance Status >= 3.
4. Recipient of living donor or deceased donor liver transplantation
5. Patients unable to understand the contents of informed consent or refuse to sign the informed consent.
6. Patients with evidence of uncontrolled or severe medical conditions requiring treatment.

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
Active Comparator: Sorafenib; Sorafenib 400mg po bid	Drug: Sorafenib; Sorafenib 400mg po bid; Other Names: Nexavar
Experimental: TACE for HCC with portal vein invasion; Antineoplastic agents are directly injected into the hepatic artery, allowing high intratumoral concentrations of drugs and thereby reducing systemic side effects. The mixture of chemotherapeutic agents and iodized oil is almost completely retained in neoplastic nodules and can remain in HCC tissue for a long time. Subsequent mechanical embolization of the artery feeding the neoplasm causes ischemic damage to the tumor and prolongs the duration of the effects of chemotherapeutic agents.	Procedure: TACE for HCC with portal vein invasion; The volume of iodized oil ranged from 2 to 12 mL, and the amount of doxorubicin ranged from 10 to 60 mg. Gelatin sponge particles were mixed with mitomycin and contrast material.Cisplatin was infused at the tumor feeder vessels as a solution with a concentration of 0.5 mg/mL at a rate of 5-10 mL/min. The total amount of cisplatin used ranged from 50 to 100 mg depending on the patient's body weight and the level of infusion.; Other Names: TACE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to Progression (Efficacy)	every 6 weeks up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival		every 6 weeks up to 3 years
objective tumor response rate	Determined by dynamic-perfusion CT scan at the end of each cycle	every 6 weeks up to 3 years
objective tumor control rate	Determined by dynamic-perfusion CT scan at the end of each cycle	every 6 weeks up to 3 years
progression-free survival		every 6 weeks up to 3 years
the adverse event rate and examine the toxicities	The investigators will evaluate the adverse event according to Common Toxicity Criteria(version 4.0)by National Cancer Institute of National Institutes of Health	every 6 weeks up to 3 years
Change of perfusion parameter		every 6 weeks up to 3 years
Alpha feto protein (AFP) responsiveness	AFP responder : 20% reduction from baseline AFP level after 6 weeks of treatment	every 6 weeks up to 3 years

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: November 20, 2011
• First Submitted That Met QC Criteria: November 24, 2011
• First Posted (Estimate): November 29, 2011

Study Record Updates

• Last Update Posted (Estimate): April 29, 2016
• Last Update Submitted That Met QC Criteria: April 28, 2016
• Last Verified: December 1, 2013

More Information

Terms related to this study

• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: STAP