Clinical Trials /

Sorafenib Chemoembolization Evaluation Controlled Trial

NCT01906216

Description:

This prospective, multicenter, randomized, controlled study aims to evaluate the efficacy and safety of sorafenib combined with transarterial chemoembolization (TACE) in advanced hepatocellular carcinoma (HCC) patients compared with sorafenib alone, and to determine the prognostic factors that influence the survival. Data on the efficacy and safety of sorafenib in combination with TACE in patients with advanced HCC are lacking. Because in western countries, advanced HCC is considered as a contraindication for TACE treatment. However, clinical practice patterns differ markedly between Asia and western countries: in Asia TACE is performed in selected advanced HCC patients. We consider sorafenib combined with TACE could achieve better survival benefit than sorafenib alone in selected advanced HCC patients.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Sorafenib Chemoembolization Evaluation Controlled Trial
  • Official Title: Sorafenib With or Without Transarterial Chemoembolization (TACE) in Advanced Hepatocellular Carcinoma : A Multicenter, Randomized, Controlled Trial

Clinical Trial IDs

  • ORG STUDY ID: XHDD-001
  • NCT ID: NCT01906216

Conditions

  • Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
SorafenibBay 43-9006, Sorafenib (Nexavar®)Sorafenib

Purpose

This prospective, multicenter, randomized, controlled study aims to evaluate the efficacy and safety of sorafenib combined with transarterial chemoembolization (TACE) in advanced hepatocellular carcinoma (HCC) patients compared with sorafenib alone, and to determine the prognostic factors that influence the survival. Data on the efficacy and safety of sorafenib in combination with TACE in patients with advanced HCC are lacking. Because in western countries, advanced HCC is considered as a contraindication for TACE treatment. However, clinical practice patterns differ markedly between Asia and western countries: in Asia TACE is performed in selected advanced HCC patients. We consider sorafenib combined with TACE could achieve better survival benefit than sorafenib alone in selected advanced HCC patients.

Detailed Description

      PRIMARY OBJECTIVE:

      To compare the overall survival of selected advanced HCC patients treated with sorafenib
      combined with TACE with sorafenib alone.

      SECONDARY OBJECTIVES:

        1. To compare the time to progression(TTP).

        2. To compare the tumor response and disease control rate according to Response Evaluation
           Criteria in Solid Tumors(RECIST), modified Response Evaluation Criteria in Solid
           Tumors(mRECIST) and European Association of Liver Disease(EASL) criteria.

        3. To compare the safety.

      OTHER OBJECTIVES:

      1. To explore the prognostic value of AFP response after treatment.

      OUTLINE: This is a multicenter, phase 3, prospective, randomized, controlled trial. Patients
      are stratified according to

        1. ECOG ( 0 vs. 1)

        2. Child-Pugh (A vs. B7)

        3. Tumor burden

             1. single vs. multiple lesions

             2. tumor size (>8cm vs. ≤8cm)

             3. vascular invasion (yes vs. no)

             4. extrahepatic metastasis (yes vs. no)

        4. Alpha fetoprotein(AFP)(≤ 200 ng/mL vs. > 200 ng/mL) Patients are randomized to 1 of 2
           treatment arms.

      ARM I: Patients receive two tablets of sorafenib (200 mg tablets) twice daily (each morning
      and evening). Patients undergo the first conventional transarterial chemoembolization (TACE)
      within 3-7 days after the first administration of sorafenib. The conventional TACE consists
      of an injection containing a mixture of chemotherapeutic agents (doxorubicin) and lipiodol
      followed by embolization with polyvinyl alcohol (PVA) or beads 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.

      ARM II: Patients receive two tablets of sorafenib (200 mg tablets) twice daily (each morning
      and evening).

      MAINTENANCE THERAPY: Standard follow-up evaluations include contrast-enhanced CT scan and
      laboratory assessment. Laboratory assessment will be performed every 4 weeks. Radiological
      follow-up (contrast-enhanced CT scan in liver and chest X-ray) will be performed during week
      4 and week 8 after initiation of treatment and thereafter every 8 weeks.
    

Trial Arms

NameTypeDescriptionInterventions
SorafenibActive ComparatorAll subjects will take two tablets of sorafenib (200 mg tablets) twice daily (each morning and evening). Sorafenib may be taken either with a low/moderate fat meal or without food. Subjects are to continue sorafenib according to the study protocol if the adverse events could be safely controlled.
  • Sorafenib
Sorafenib combined with TACEExperimentalSorafenib will be supplied as 200 mg tablets. All subjects will take two tablets of sorafenib (200 mg tablets) twice daily (each morning and evening). In addition, the subjects in this arm will receive the treatment of conventional transarterial chemoembolization. In all cases, TACE consists of an injection containing a mixture of chemotherapeutic agents(doxorubicin) and lipiodol followed by embolization with polyvinyl alcohol (PVA) or beads.
  • Sorafenib

Eligibility Criteria

        Inclusion Criteria:

          1. Prior informed consent

          2. Advanced stage HCC/ Barcelona Clinic Liver Cancer(BCLC) C stage

          3. Confirmed Diagnosis of HCC:

               1. Cirrhotic subjects: Clinical diagnosis by Asian Pacific Association for the Study
                  of the Liver(AASLD) criteria.

               2. Non-cirrhotic subjects: for subjects without cirrhosis, histological or
                  cytological confirmation is mandatory

               3. Documentation of original biopsy for diagnosis is acceptable

          4. Child Pugh class A without ascites or hepatic encephalopathy

          5. Eastern Cooperative Oncology Group(ECOG) Performance Status of 0-1

          6. At least one uni-dimensional lesion measurable by CT-scan or MRI according to the
             RECIST, 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 subjects ≥ 18 years of age

          8. Ability to swallow oral medications

          9. Life expectancy of at least 12 weeks

         10. 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 function 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. Alanine aminotransferase(ALT) and aspartate aminotransferase(AST) < 5 x upper
                  limit of normal

               7. Blood urea nitrogen(BUN) and creatinine < 1.5 x upper limit of normal

               8. International normalized ratio(INR) < 1.7, or prothrombin time(PT) < 4 seconds
                  above control

        Exclusion Criteria:

          1. Diffuse HCC or tumor burden ≥50% of liver parenchyma

          2. Main portal vein obstruction, vascular invasion in hepatic vein or inferior vena cava

          3. Presence of metastasis in biliary tract,brain or bone

          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. Other molecular target drugs ongoing or completed < 4 weeks prior to the baseline scan

          8. Prior transarterial embolization or systemic chemotherapy

          9. Any ≥ CTC adverse events(AEs) 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 3.0), except for
             Hepatitis B virus(HBV) and hepatitis C virus(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(within 6 months of randomization)which could affect the evaluation of the
             study drug

         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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival
Time Frame:The final analysis will occur when the expected number of death (173 events) is reached. Up to 2.5 years
Safety Issue:
Description:Overall survival (OS) analysis is measured from the time of randomization until death occurred from any cause.

Secondary Outcome Measures

Measure:Time to progression
Time Frame:The time to progression will be assessed at the end of the study, up to 2.5 years
Safety Issue:
Description:The time to progression is measured from the time of randomization to the radiologically confirmed progression.
Measure:Tumor response
Time Frame:Tumor response will be assessed up to 2.5 years
Safety Issue:
Description: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.
Measure:Adverse events
Time Frame:The adverse events will be assessed up to 2.5 years.
Safety Issue:
Description:The terms and grade of adverse events will be presented according to the Common Terminology Criteria for Adverse Events(CTCAE:version 4.0)

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fourth Military Medical University

Trial Keywords

  • Hepatocellular carcinoma
  • sorafenib
  • transarterial chemoembolization

Last Updated

July 31, 2019