Tenofovir Antiviral Therapy Following Transarterial Chemoembolization for HBV Related Hepatocellular Carcinoma

NCT01872988 | Terminated Phase 3 DMC

• 2 other identifiers: CF12045JIRB11-036-A
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Chronic Hepatitis B; Hepatocellular Carcinoma

Keywords

antiviral therapy; intermediate stage; hepatitis B virus

Outcome Measures

Primary Outcomes (1)

• overall survival

  up to 3-year

Secondary Outcomes (2)

• time to tumor progression

  1- and 3-year

• time to liver decompensation

  1- and 3-year

Study Arms (2)

Tenofovir treatment

ACTIVE COMPARATOR

Start to administer Tenofovir treatment 300mg PO QD within 2 weeks after the 1st TACE. Maximum duration of tenofovir treatment: 3 years.

Drug: Tenofovir

Placebo

PLACEBO COMPARATOR

Start to administer placebo 1 Tab PO QD within 2 weeks after the 1st TACE. Maximum duration of tenofovir treatment: 3 years.

Drug: Placebo

Interventions

Tenofovir DRUG

Administer Tenofovir to HCC patients who are indicated for TACE after randomization

Also known as: Viread

Tenofovir treatment

Placebo DRUG

Administer Placebo to HCC patients who are indicated for TACE after randomization

Placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• any vascular invasion by tumors
• extra-hepatic metastasis
• concurrent any other malignancy
• concomitant immunosuppressive therapy
• HCC recurrence within 2 years of previous curative treatment
• antiviral therapy for chronic hepatitis B within 6 months before HCC diagnosis
• 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) -

Sponsors & Collaborators

• Taichung Veterans General Hospital: lead
• Gilead Sciences: collaborator
• Taipei Institute of Pathology: collaborator

Study Sites (4)

Chia-Yi Christine Hospital

Chiayi City, 539, Taiwan

Location

E-Da Hospital

Kaohsiung City, 824, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 407, Taiwan

Location

Mackay Memorial Hosp

Taipei, 104, Taiwan

Location

Related Publications (2)

• Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Sola R, Rodes J, Bruix J; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1734-9. doi: 10.1016/S0140-6736(02)08649-X.

  PMID: 12049862 BACKGROUND

• Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002 May;35(5):1164-71. doi: 10.1053/jhep.2002.33156.

  PMID: 11981766 BACKGROUND

MeSH Terms

Conditions

Hepatitis B, Chronic; Carcinoma, Hepatocellular; Hepatitis B

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Chun-Ying Wu, MD, PhD, MPH

  Taichung Veterans General Hospital

  PRINCIPAL INVESTIGATOR

• Jaw-Town Lin, MD, PhD

  Fu Jen Catholic University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 30, 2013
• First Posted: June 7, 2013
• Study Start: September 1, 2012
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: September 4, 2014

Record last verified: 2014-09

Locations

TW (4)