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TACE With or Without Sorafenib in Intermediate Stage Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT02529761
Recruitment Status : Recruiting
First Posted : August 20, 2015
Last Update Posted : September 22, 2015
Sponsor:
Information provided by (Responsible Party):
Guohong Han, Fourth Military Medical University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Sorafenib Procedure: TACE Not Applicable

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  (Clinical Trial)
Estimated Enrollment : 330 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Transarterial Chemoembolization (TACE) With or Without Sorafenib in Intermediate Stage Hepatocellular Carcinoma: a Multicenter Prospective Nonrandomized Study
Study Start Date : August 2015
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : October 2018

Resource links provided by the National Library of Medicine


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 Name: •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 Name: 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 Name: conventional transarterial chemeombolization




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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)

  4. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02529761


Contacts
Contact: Guohong Han, MD +862984771528 guohhan@126.com
Contact: Wei Bai, MD chris41532@163.com

Locations
China, Shaanxi
Xijing Hospital of digestive disease, Fourth Military Medical University Recruiting
Xi'an, Shaanxi, China, 710032
Contact: Han       hangh@fmmu.edu.cn   
Principal Investigator: Guohong Han, MD,Ph.D         
Sponsors and Collaborators
Fourth Military Medical University
Investigators
Principal Investigator: Guohong Han, MD Xijing Hospital of Digestive Disease, Fourth Military Medical University

Publications of Results:
Responsible Party: Guohong Han, Director, Fourth Military Medical University
ClinicalTrials.gov Identifier: NCT02529761     History of Changes
Other Study ID Numbers: S-T 002
First Posted: August 20, 2015    Key Record Dates
Last Update Posted: September 22, 2015
Last Verified: September 2015

Keywords provided by Guohong Han, Fourth Military Medical University:
HCC
sorafenib
TACE
overall survival

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Chlorotrianisene
Niacinamide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Estrogens, Non-Steroidal
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal