Tenofovir Antiviral Therapy Following Transarterial Chemoembolization for HBV Related Hepatocellular Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Taichung Veterans General Hospital
Sponsor:
Collaborators:
Gilead Sciences
Taipei Institute of Pathology, Taiwan
Information provided by (Responsible Party):
Chun-Ying Wu, Taichung Veterans General Hospital
ClinicalTrials.gov Identifier:
NCT01872988
First received: January 30, 2013
Last updated: June 7, 2013
Last verified: June 2013
  Purpose

Hepatocellular carcinoma (HCC) is one of the most common solid cancers worldwide, and chronic hepatitis B virus (HBV) infection is the most common etiology of HCC in Asia. Transarterial chemoembolization (TACE) is the standard treatment for patients with unresectable HCC in the BCLC intermediate stage, but the HCC recurrence rates and long-term mortality rates are quite high. These intermediate-staged HCC patients usually need repeated TACE due to tumor recurrence, and they may die of HCC progression or liver decompensation after repeated TACE. Improved liver function and decreased liver disease progression due to oral antiviral therapy have been proven to be effective for chronic hepatitis B, and oral antiviral therapy may keep better liver reserve and provide better chance for HCC patients received TACE. In addition, chronic HBV infection is one of the most important factors for HCC development, and antiviral therapy can improve the outcomes after curative treatment. However, the evidence of improving outcomes of HCC patients underwent TACE by oral antiviral therapy is lacking. Moreover, Tenofovir Disoproxil Fumarate (TDF) is one of the most potent oral antiviral agents, and its safety and very low long-term viral resistance rate have been also reported. There is no study to evaluate the impacts of TDF for HBV-related HCC patients underwent TACE. Until now, routine antiviral therapy for HBV-related HCC patients underwent TACE has still not been recommended by current guidelines. The hypothesis of this study is that a potent oral antiviral therapy for patients with HBV-related HCC patients receiving TACE improve patients' outcomes


Condition Intervention Phase
Chronic Hepatitis B
Hepatocellular Carcinoma
Drug: Tenofovir
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Tenofovir Disoproxil Fumarate Improves Outcomes Following Palliative Transarterial Chemoembolization for Hepatitis B Virus Related Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Taichung Veterans General Hospital:

Primary Outcome Measures:
  • overall survival [ Time Frame: up to 3-year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • time to tumor progression [ Time Frame: 1- and 3-year ] [ Designated as safety issue: No ]
  • time to liver decompensation [ Time Frame: 1- and 3-year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 320
Study Start Date: September 2012
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tenofovir treatment
Start to administer Tenofovir treatment 300mg PO QD within 2 weeks after the 1st TACE. Maximum duration of tenofovir treatment: 3 years.
Drug: Tenofovir
Administer Tenofovir to HCC patients who are indicated for TACE after randomization
Other Name: Viread
Placebo Comparator: Placebo
Start to administer placebo 1 Tab PO QD within 2 weeks after the 1st TACE. Maximum duration of tenofovir treatment: 3 years.
Drug: Placebo
Administer Placebo to HCC patients who are indicated for TACE after randomization
Other Name: Placebo

Detailed Description:

This is randomized double-blind placebo-controlled trial that will be conducted in referral teaching hospitals in Taiwan. This trial will recruit 320 patients fulfilling all of the following criteria: patients more than 20 years old, HCCs diagnosed by AASLD image criteria or pathology, medium-sized HCCs in BCLC intermediate stage and not more than 5 cm in maximum diameter and not more than 5 tumors that TACE is indicated, chronic HBV carrier (HBsAg+) with detectable HBV DNA in blood, ECOG performance status (PST) 0-2, Child-Pugh score ≦7, serum bilirubin < 2 mg/dL and prothrombin time (PT) prolongation < 3 seconds, and willingness to adhere to treatment and follow-up plans. Patients are ineligible if they have any of the following exclusion criteria: any vascular invasion by tumors, extra-hepatic metastasis, concurrent any other malignancy, concomitant immunosuppressive therapy, previous any HCC treatment, previous or current any antiviral therapy for HBV, concomitant other therapies for HCC except TACE, liver cirrhosis with severe gastroesophageal varices (EVF3 or with red color sign), poorly-controlled ascites or hepatic encephalopathy, contraindication for invasive procedures such as recent gastrointestinal bleeding or cerebral hemorrhage, contraindication to TACE such as allergy to contrast, pregnancy, sepsis, etc., chronic renal failure with eGFR < 60, concurrent any other chronic viral hepatitis with HCV, HDV, or HIV). The Primary endpoints of this study will be 1-, 3-year overall survival, and the secondary endpoints of this study will be time to tumor progression and time to liver decompensation.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. more than 20 years old
  2. HCCs diagnosed by AASLD image criteria or pathology
  3. Intermediate-stage HCCs that TACE is indicated
  4. chronic HBV carrier with detectable HBV DNA in blood
  5. ECOG performance status (PST) 0-2
  6. Child-Pugh score ≦7
  7. serum bilirubin < 2 mg/dL
  8. prothrombin time prolongation < 3 seconds
  9. willingness to adhere to treatment and follow-up plans -

Exclusion Criteria:

  1. any vascular invasion by tumors
  2. extra-hepatic metastasis
  3. concurrent any other malignancy
  4. concomitant immunosuppressive therapy
  5. HCC recurrence within 2 years of previous curative treatment
  6. antiviral therapy for chronic hepatitis B within 6 months before HCC diagnosis
  7. concomitant other therapies for HCC except TACE
  8. liver cirrhosis with severe gastroesophageal varices (EVF3 or with red color sign), poorly-controlled ascites or hepatic encephalopathy
  9. contraindication for invasive procedures such as recent gastrointestinal bleeding or cerebral hemorrhage
  10. contraindication to TACE such as allergy to contrast, pregnancy, sepsis, etc.
  11. chronic renal failure with eGFR < 60
  12. concurrent any other chronic viral hepatitis with HCV, HDV, or HIV) -
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01872988

Contacts
Contact: Chun-Ying Wu, MD, PhD, MPH 886-4-23592525 ext 3304 chun@vghtc.gov.tw
Contact: Teng-Yu Lee, MD 886-4-23592525 ext 3316 tengyulee@gmail.com

Locations
Taiwan
Chia-Yi Christine Hospital Not yet recruiting
Chia-Yi, Taiwan, 539
Contact: Chi-Yi Chen, MD    886-5-2765041    01290@cych.org.tw   
Principal Investigator: Chi-Yi Chen, MD         
E-Da Hospital Recruiting
Kaohsiung, Taiwan, 824
Contact: Yao-Chun Hsu, MD    886-7-6150011 ext 2980    gatsbyhsu@yahoo.com.tw   
Principal Investigator: Yao-Chun Hsu, MD, MSc         
Taichung Veterans General Hospital Recruiting
Taichung, Taiwan, 407
Contact: Chun-Ying Wu, MD    886-4-23592525 ext 3304    chun@vghtc.gov.tw   
Contact: Teng-Yu Lee, MD    886-4-23592525 ext 3316    tengyulee@gmail.com   
Principal Investigator: Chun-Ying Wu, MD         
Sub-Investigator: Teng-Yu Lee, MD         
Sub-Investigator: Jen-I Hwang, MD         
Mackay Memorial Hosp Not yet recruiting
Taipei, Taiwan, 104
Contact: Wen-Hsiung Chang, MD    02-2543-3535    d220533864@yahoo.com.tw   
Principal Investigator: Wen-Hsiung Chang, MD         
Sponsors and Collaborators
Taichung Veterans General Hospital
Gilead Sciences
Taipei Institute of Pathology, Taiwan
Investigators
Principal Investigator: Chun-Ying Wu, MD, PhD, MPH Taichung Veterans General Hospital
Study Chair: Jaw-Town Lin, MD, PhD Fu Jen Catholic University
  More Information

Additional Information:
Publications:
Responsible Party: Chun-Ying Wu, Professor, Taichung Veterans General Hospital
ClinicalTrials.gov Identifier: NCT01872988     History of Changes
Other Study ID Numbers: CF12045, JIRB11-036-A
Study First Received: January 30, 2013
Last Updated: June 7, 2013
Health Authority: Taiwan: Department of Health

Keywords provided by Taichung Veterans General Hospital:
antiviral therapy
intermediate stage
hepatitis B virus

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Hepatitis, Viral, Human
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Antiviral Agents
Tenofovir
Tenofovir disoproxil
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014