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出境医 / 临床实验 / Drug-eluting Bead Transarterial Chemoembolisation (DEB-TACE) Versus (VS) Conventional Transarterial Chemoembolisation (cTACE) for Unresectable Hepatocellualr Carcinoma (HCC)

Drug-eluting Bead Transarterial Chemoembolisation (DEB-TACE) Versus (VS) Conventional Transarterial Chemoembolisation (cTACE) for Unresectable Hepatocellualr Carcinoma (HCC)

Study Description
Brief Summary:
this multi-center prospective cohort study is to evaluate the efficacy and the safety of drug-eluting bead TACE compared with conventional TACE in terms of objective response in unresectable HCC

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Procedure: DEB-TACE Procedure: cTACE Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 344 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Drug-eluting Bead TACE VS Conventional TACE for Unresectable Hepatocellular Carcinoma: a Multicenter, Prospective Cohort Study
Estimated Study Start Date : September 15, 2020
Estimated Primary Completion Date : June 15, 2022
Estimated Study Completion Date : June 15, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: DEB-TACE
172 subjects in this study group will be receive the treatment of drug-eluting bead TACE
Procedure: DEB-TACE
Patients in the DEB-TACE group received a maximum dose of 4 ml of DC bead (diameter 75-500 um) loaded with a maximum dose of 150 mg of anthracyclines drugs, such as doxorubicin. The anticancer agents and the diameter of DC Bead for individual patient will be selected according to the common clinical practice of each center. Treatment endpoint consisted of stasis of flow within feeding vessel(s) or completed delivery of maximum single-session dose of 150 mg doxorubicin. TACE will be repeated "on demand" according to the radiological response.
Other Name: drug-eluting bead transarterial chemoembolisation

Active Comparator: cTACE
172 subjects in this study group will be receive the treatment of conventional TACE
Procedure: cTACE
Patients in the cTACE group were treated with anthracyclines, such as doxorubicin, in a mixture of lipiodol. Administration of the anticancer in oil emulsion was followed by injection of embolic materials such as gelfoam or PVA particles until complete stasis in segmental or subsegmental arterial branches. the tumor-feeding vessels should be superselected whenever possible. The anticancer agents for individual patient will be selected according to the common clinical practice of each center. TACE will be repeated "on demand" according to the radiological response.
Other Name: conventional transarterial chemoembolisation

Outcome Measures
Primary Outcome Measures :
  1. Objective response rate [ Time Frame: Tumor response will be assessed at week 4 and week 12 after initiation of treatment and thereafter every 8 weeks, up to 1 year ]
    the percentage of patients who achieved complete response (CR) and partial response (PR) as the best response, according to the modified Response Evaluation Criteria In Solid Tumours (mRECIST) criteria


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: The last patient has been on study for 1year ]
    Overall survival (OS) is measured from the treatment start until all-cause death or the last follow-up date

  2. Time to progression [ Time Frame: The last patient has been on study for 1year ]
    Time to progression is measured from the treatment start to the radiologically confirmed progression

  3. Adverse event [ Time Frame: The adverse event will be assessed during in hospital and every 4 weeks, up to 1year ]
    The terms and grade of adverse event will be present according to the Common Terminology Criteria for Adverse Event (CTCAE version 4.0)

  4. Progression-free survival [ Time Frame: The last patient has been on study for 1year ]
    Progression-free survival (PFS) is measured from the treatment start until all-cause death or untreatable progression (vascular invasion, extra hepatic spread, the Eastern Cooperative Oncology Group (ECOG) performance status >2, and Child-Pugh grade over C, but except hepatic new nodule)

  5. Time to response [ Time Frame: The last patient has been on study for 1year ]
    Time to response (TTR) is measured from the treatment start to the firstly radiologically confirmed complete response or partial response.

  6. Duration of response [ Time Frame: The last patient has been on study for 1year ]
    Duration of response (DOR) is measured from the first-time confirmed complete response or partial response to the date of radiological progression


Eligibility Criteria
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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. Confirmed Diagnosis of HCC: a. Cirrhotic subjects: Clinical diagnosis by American Association for the Study of Liver Diseases (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. b. Non-cirrhotic subjects: For subjects without cirrhosis, histological or cytological confirmation is mandatory. Documentation of original biopsy for diagnosis is acceptable
  3. Patients with unresectable Barcelona Clinic Liver Cancer (BCLC) stage A and BCLC B, and all patients have a intermediate or high tumor burden (the diameter of largest tumor plus tumor number is more than 6)
  4. Child Pugh class A/B(7) class without decompensated liver cirrhosis.
  5. ECOG Performance Status 0 score
  6. At least one uni-dimensional lesion measurable by MRI or CT according to the RECIST 1.1 criteria
  7. Male or female subject larger than 18 years of age
  8. Life expectance of at least 12 weeks.
  9. 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
  10. 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. Portal vein or any vascular invasion
  2. Presence of extra hepatic spread
  3. Presence of metastasis in biliary tract or obstruction of biliary tract
  4. Presence of metastasis in brain or presence of symptom of the brain metastasis but lack of further examination to exclude brain metastasis
  5. 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
  6. 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
  7. History of cardiac disease:

    1. Congestive heart failure >New York Heart Association (NYHA) class 2
    2. Uncontrolled hypertension
  8. Known history of HIV infection
  9. Patients who have previously been receiving any treatments against HCC
  10. Active clinically serious infections (> grade 2 NCI-CTCAE Version 4.0), except for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection
  11. Contraindication of Anthracyclines administration, such as Doxorubicin
  12. Concurrent with other cancer
  13. Pregnant or breast-feeding subjects
  14. Women of childbearing age did not take any contraceptive measures
  15. Clinically significant gastrointestinal bleeding within 12 weeks prior to start of study
  16. Major surgery within 3 weeks prior to start of study drug (e.g. thoracolaparotomy is not allowed, but noninvasive surgery, e.g. biopsy, is allowed)
Contacts and Locations

Contacts
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Contact: Guohong Han, MD PHD +86-2984771528 hangh@fmmu.edu.cn
Contact: Dongdong Xia, MD +86-2984771528 xiadongdong1026@163.com

Locations
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China, Shaanxi
Xijing Hospital of Digestive Diseases, Fourth Military Medical University
Xi'an, Shaanxi, China, 710032
Sponsors and Collaborators
Air Force Military Medical University, China
Tracking Information
First Submitted Date  ICMJE May 29, 2019
First Posted Date  ICMJE May 31, 2019
Last Update Posted Date February 5, 2020
Estimated Study Start Date  ICMJE September 15, 2020
Estimated Primary Completion Date June 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2019)
Objective response rate [ Time Frame: Tumor response will be assessed at week 4 and week 12 after initiation of treatment and thereafter every 8 weeks, up to 1 year ]
the percentage of patients who achieved complete response (CR) and partial response (PR) as the best response, according to the modified Response Evaluation Criteria In Solid Tumours (mRECIST) criteria
Original Primary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
Objective response rate [ Time Frame: Tumor response will be assessed at week 4 and week 12 after initiation of treatment and thereafter every 8 weeks, up to 1 year ]
the percentage of patients who achieved complete response (CR) and partial response (PR) as the best response, according to mRECIST criteria
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2019)
  • Overall survival [ Time Frame: The last patient has been on study for 1year ]
    Overall survival (OS) is measured from the treatment start until all-cause death or the last follow-up date
  • Time to progression [ Time Frame: The last patient has been on study for 1year ]
    Time to progression is measured from the treatment start to the radiologically confirmed progression
  • Adverse event [ Time Frame: The adverse event will be assessed during in hospital and every 4 weeks, up to 1year ]
    The terms and grade of adverse event will be present according to the Common Terminology Criteria for Adverse Event (CTCAE version 4.0)
  • Progression-free survival [ Time Frame: The last patient has been on study for 1year ]
    Progression-free survival (PFS) is measured from the treatment start until all-cause death or untreatable progression (vascular invasion, extra hepatic spread, the Eastern Cooperative Oncology Group (ECOG) performance status >2, and Child-Pugh grade over C, but except hepatic new nodule)
  • Time to response [ Time Frame: The last patient has been on study for 1year ]
    Time to response (TTR) is measured from the treatment start to the firstly radiologically confirmed complete response or partial response.
  • Duration of response [ Time Frame: The last patient has been on study for 1year ]
    Duration of response (DOR) is measured from the first-time confirmed complete response or partial response to the date of radiological progression
Original Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
  • Overall survival [ Time Frame: The last patient has been on study for 1year ]
    Overall survival (OS) is measured from the treatment start until all-cause death or the last follow-up date
  • Time to progression [ Time Frame: The last patient has been on study for 1year ]
    Time to progression is measured from the treatment start to the radiologically confirmed progression
  • Adverse event [ Time Frame: The adverse event will be assessed during in hospital and every 4 weeks, up to 1year ]
    The terms and grade of adverse event will be present according to the Common Terminology Criteria for Adverse Event (CTCAE version 4.0)
  • Progression-free survival [ Time Frame: The last patient has been on study for 1year ]
    Progression-free survival (PFS) is measured from the treatment start until all-cause death or untreatable progression (vascular invasion, extra hepatic spread, ECOG performance status >2, and Child-Pugh grade over C, but except hepatic new nodule)
  • Time to response [ Time Frame: The last patient has been on study for 1year ]
    Time to response (TTR) is measured from the treatment start to the firstly radiologically confirmed complete response or partial response.
  • Duration of response [ Time Frame: The last patient has been on study for 1year ]
    Duration of response (DOR) is measured from the first-time confirmed complete response or partial response to the date of radiological progression
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Drug-eluting Bead Transarterial Chemoembolisation (DEB-TACE) Versus (VS) Conventional Transarterial Chemoembolisation (cTACE) for Unresectable Hepatocellualr Carcinoma (HCC)
Official Title  ICMJE Efficacy and Safety of Drug-eluting Bead TACE VS Conventional TACE for Unresectable Hepatocellular Carcinoma: a Multicenter, Prospective Cohort Study
Brief Summary this multi-center prospective cohort study is to evaluate the efficacy and the safety of drug-eluting bead TACE compared with conventional TACE in terms of objective response in unresectable HCC
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Hepatocellular Carcinoma
Intervention  ICMJE
  • Procedure: DEB-TACE
    Patients in the DEB-TACE group received a maximum dose of 4 ml of DC bead (diameter 75-500 um) loaded with a maximum dose of 150 mg of anthracyclines drugs, such as doxorubicin. The anticancer agents and the diameter of DC Bead for individual patient will be selected according to the common clinical practice of each center. Treatment endpoint consisted of stasis of flow within feeding vessel(s) or completed delivery of maximum single-session dose of 150 mg doxorubicin. TACE will be repeated "on demand" according to the radiological response.
    Other Name: drug-eluting bead transarterial chemoembolisation
  • Procedure: cTACE
    Patients in the cTACE group were treated with anthracyclines, such as doxorubicin, in a mixture of lipiodol. Administration of the anticancer in oil emulsion was followed by injection of embolic materials such as gelfoam or PVA particles until complete stasis in segmental or subsegmental arterial branches. the tumor-feeding vessels should be superselected whenever possible. The anticancer agents for individual patient will be selected according to the common clinical practice of each center. TACE will be repeated "on demand" according to the radiological response.
    Other Name: conventional transarterial chemoembolisation
Study Arms  ICMJE
  • Experimental: DEB-TACE
    172 subjects in this study group will be receive the treatment of drug-eluting bead TACE
    Intervention: Procedure: DEB-TACE
  • Active Comparator: cTACE
    172 subjects in this study group will be receive the treatment of conventional TACE
    Intervention: Procedure: cTACE
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 29, 2019)
344
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 15, 2022
Estimated Primary Completion Date June 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Prior informed consent
  2. Confirmed Diagnosis of HCC: a. Cirrhotic subjects: Clinical diagnosis by American Association for the Study of Liver Diseases (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. b. Non-cirrhotic subjects: For subjects without cirrhosis, histological or cytological confirmation is mandatory. Documentation of original biopsy for diagnosis is acceptable
  3. Patients with unresectable Barcelona Clinic Liver Cancer (BCLC) stage A and BCLC B, and all patients have a intermediate or high tumor burden (the diameter of largest tumor plus tumor number is more than 6)
  4. Child Pugh class A/B(7) class without decompensated liver cirrhosis.
  5. ECOG Performance Status 0 score
  6. At least one uni-dimensional lesion measurable by MRI or CT according to the RECIST 1.1 criteria
  7. Male or female subject larger than 18 years of age
  8. Life expectance of at least 12 weeks.
  9. 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
  10. 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. Portal vein or any vascular invasion
  2. Presence of extra hepatic spread
  3. Presence of metastasis in biliary tract or obstruction of biliary tract
  4. Presence of metastasis in brain or presence of symptom of the brain metastasis but lack of further examination to exclude brain metastasis
  5. 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
  6. 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
  7. History of cardiac disease:

    1. Congestive heart failure >New York Heart Association (NYHA) class 2
    2. Uncontrolled hypertension
  8. Known history of HIV infection
  9. Patients who have previously been receiving any treatments against HCC
  10. Active clinically serious infections (> grade 2 NCI-CTCAE Version 4.0), except for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection
  11. Contraindication of Anthracyclines administration, such as Doxorubicin
  12. Concurrent with other cancer
  13. Pregnant or breast-feeding subjects
  14. Women of childbearing age did not take any contraceptive measures
  15. Clinically significant gastrointestinal bleeding within 12 weeks prior to start of study
  16. Major surgery within 3 weeks prior to start of study drug (e.g. thoracolaparotomy is not allowed, but noninvasive surgery, e.g. biopsy, is allowed)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Guohong Han, MD PHD +86-2984771528 hangh@fmmu.edu.cn
Contact: Dongdong Xia, MD +86-2984771528 xiadongdong1026@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03969576
Other Study ID Numbers  ICMJE DEB-TACE-HCC
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Guohong Han, Air Force Military Medical University, China
Study Sponsor  ICMJE Air Force Military Medical University, China
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Air Force Military Medical University, China
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP