TACE With or Without Sorafenib in Intermediate Stage Hepatocellular Carcinoma

July 31, 2019 updated by: Guohong Han, Air Force Military Medical University, China

Transarterial Chemoembolization (TACE) With or Without Sorafenib in Intermediate Stage Hepatocellular Carcinoma: a Multicenter Prospective Nonrandomized Study

This multicenter prospective nonrandomized study is to evaluate the efficacy of TACE combined with sorafenib compared with TACE monotherapy in term of overall survival in intermediate-stage HCC.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Sorafenib, a multikinase inhibitor, has been successfully applied for solid tumors such as renal cancer and HCC.

According to the Barcelona Clinic Liver Cancer (BCLC) staging classification, transarterial chemoembolization (TACE) has been recommended as a first line-therapy for patients at intermediate stage - BCLC B class (multinodular asymptomatic tumors without an invasive pattern).

Because sorafenib may improve the efficacy of locoregional therapy by decreasing post-TACE angiogenesis, sorafenib in combination with TACE has attracted considerable attention as a promising therapy

Study Type

Interventional

Enrollment (Anticipated)

330

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shaanxi
      • Xi'an, Shaanxi, China, 710032
        • Recruiting
        • Xijing Hospital of digestive disease, Fourth Military Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  1. Prior informed consent
  2. Intermediate stage HCC/ BCLC B stage

  3. Confirmed Diagnosis of HCC:

    1. Cirrhotic subjects: Clinical diagnosis by AASLD criteria. HCC can be defined in cirrhotic subjects by one imaging technique (CT scan, MRI, or second generation contrast ultrasound) showing a nodule larger than 2 cm with contrast uptake in the arterial phase and washout in venous or late phases or two imaging techniques showing this radiological behavior for nodules of 1-2 cm in diameter. Cytohistological confirmation is required for subjects who do not fulfill these eligibility criteria.
    2. Non-cirrhotic subjects: For subjects without cirrhosis, histological or cytological confirmation is mandatory. Documentation of original biopsy for diagnosis is acceptable
  4. Child Pugh class A/B(7) class without ascites or hepatic encephalopathy
  5. ECOG Performance Status of 0-1

  6. At least one uni-dimensional lesion measurable by CT-scan or MRI according to the RECIST 1.1, mRECIST and EASL criteria, respectively.

    1. Single lesion>5cm
    2. 2-3 lesions, at least one lesion>3cm; if more than 4 lesions, no limitation of the tumor size, but the sum of size of all tumor lesions should be less than 50% of liver parenchyma.
  7. Male or female subject ≥ 18 years of age
  8. Ability to swallow oral medications
  9. Life expectancy of at least 12 weeks
  10. Pregnancy test negative within 14 days before treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 4 weeks after the completion of trial

  11. Adequate bone marrow, liver and renal functions as assessed by central lab by means of the following laboratory requirements from samples within 7 days prior to randomization:

    1. Hemoglobin > 9.0 g/dl
    2. Absolute neutrophil count (ANC) >1,500/mm3
    3. Platelet count ≥50x109/L
    4. ALB ≥28g/L
    5. Total bilirubin < 2 mg/dL
    6. ALT and AST < 5 x upper limit of normal
    7. BUN and creatinine < 1.5 x upper limit of normal
    8. INR < 1.7, or PT < 4 seconds above control

Exclusion Criteria:

  1. Diffuse HCC or tumor size ≥50% of liver parenchyma
  2. Vascular invasion
  3. Presence of extrahepatic metastasis
  4. Poor blood supply for the liver tumor lesions; poor blood supply refers that the tumor lesions fail to show obvious contrast uptake in the arterial phase and washout in venous or late phases by CT scan or MRI

  5. Any contraindications for hepatic embolization procedures:

    1. Known hepatofugal blood flow
    2. Known porto-systemic shunt
    3. Renal failure / insufficiency requiring hemo-or peritoneal dialysis
  6. Target lesions having previously been treated with local therapy such as resection of HCC, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI)
  7. Investigational drugs or other molecular target drugs ongoing or completed < 4 weeks prior to the baseline scan
  8. Prior transarterial embolization or anti-tumor systemic chemotherapy
  9. Any ≥ CTC AE grade 2 acute toxic effects of any prior local treatment
  10. Patients with untreated varices or active bleeding

  11. History of cardiac disease:

    1. Congestive heart failure >New York Heart Association (NYHA) class 2
    2. Uncontrolled hypertension
  12. Known history of HIV infection
  13. Active clinically serious infections (> grade 2 NCI-CTCAE Version 4.0), except for HBV and HCV infection
  14. Clinically significant gastrointestinal bleeding within 4 weeks prior to start of study drug
  15. Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months prior to the first dose of study drug
  16. Previous or concurrent cancer that is distinct in primary site or histology from HCC. Any cancer curatively treated >3 years prior to entry is permitted
  17. Any contraindication for sorafenib or doxorubicin administration
  18. Pregnant or breast-feeding subjects
  19. Any disease which could affect the evaluation of the study drug: unstable angina, active CAD, uncontrolled arrhythmias, and myocardial infarction
  20. Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study
  21. Major surgery within 4 weeks prior to start of study drug (e.g. thoracolaparotomy is not allowed, but noninvasive surgery, e.g. biopsy, is allowed)
  22. Autologous bone marrow transplant or stem cell rescue within 1 year prior to start of study drug
  23. History of organ allograft

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sorafenib combined with TACE
220 subjects in this study group will receive the treatment of sorafenib combined with conventional TACE.
Drug: Sorafenib
Sorafenib will be supplied as 200 mg tablets. All subjects will take two tablets of sorafenib (200 mg tablets) twice daily (each morning and evening).
Other Names:
  • •Bay 43-9006, Sorafenib (Nexavar®)
Procedure: TACE
The first treatment of TACE should be completed within 3-7 days after the administration of sorafenib started. In all cases, TACE consists of an injection containing a mixture of chemotherapeutic agents and lipiodol followed by embolization with polyvinyl alcohol (PVA) particles until complete stasis was achieved in the tumor-feeding vessels.Tumor-feeding vessels should be selected/superselected whenever possible. TACE will be repeated "on demand" depending on the radiological response.
Other Names:
  • conventional transarterial chemeombolization
Active Comparator: TACE monotherapy
110 subjects in this study group will receive the treatment of conventional TACE monotherapy.
Procedure: TACE
The first treatment of TACE should be completed within 3-7 days after the administration of sorafenib started. In all cases, TACE consists of an injection containing a mixture of chemotherapeutic agents and lipiodol followed by embolization with polyvinyl alcohol (PVA) particles until complete stasis was achieved in the tumor-feeding vessels.Tumor-feeding vessels should be selected/superselected whenever possible. TACE will be repeated "on demand" depending on the radiological response.
Other Names:
  • conventional transarterial chemeombolization

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: The last patient has been on study for 1.5 year
Overall survival analysis is measured from the treatment start until death occurred from any cause
The last patient has been on study for 1.5 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to progression
Time Frame: The time to progression will be assessed at the end of the study, up to 3 years
The time to progression is measured from the treatment start to the radiologically confirmed progression
The time to progression will be assessed at the end of the study, up to 3 years
Tumor response
Time Frame: Tumor response will be assessed at week 4 and week 8 after initiation of treatment and thereafter every 8 weeks (±7 days), up to 3 years
Tumor response will be evaluated according to RECIST, mRECIST and EASL criteria, respectively. Tumor response will be presented in the terms of complete response, partial response, stable disease and progression disease
Tumor response will be assessed at week 4 and week 8 after initiation of treatment and thereafter every 8 weeks (±7 days), up to 3 years
Adverse events
Time Frame: The adverse events will be assessed every 4 weeks, up to 3 years
The terms and grade of adverse events will be presented according to the Common Terminology Criteria for Adverse Events(CTCAE:version 4.0)
The adverse events will be assessed every 4 weeks, up to 3 years
Prognostic factor
Time Frame: The analysis will be perfomed when the last patient has been on study for 1.5 year
The Cox proportional model will be used to assess the prognostic factors
The analysis will be perfomed when the last patient has been on study for 1.5 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Air Force Military Medical University, China

Investigators

  • Principal Investigator: Guohong Han, MD, Xijing Hospital of digestive disease, Fourth Military Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2015

Primary Completion (Anticipated)

August 1, 2021

Study Completion (Anticipated)

October 1, 2021

Study Registration Dates

First Submitted

August 18, 2015

First Submitted That Met QC Criteria

August 19, 2015

First Posted (Estimate)

August 20, 2015

Study Record Updates

Last Update Posted (Actual)

August 1, 2019

Last Update Submitted That Met QC Criteria

July 31, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • S-T 002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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