Chemoembolization With or Without Antiviral Therapy for Unresectable HBV-related HCC With Low HBV DNA Replication

NCT01894269 | Unknown Phase 4 DMC

• 1 other identifier: sysucc-HCC010
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Although it is commonly accepted that antiviral therapy should be commenced before or during hepatocellular carcinoma (HCC) treatment if the patients have high viral loads and elevated ALT or total bilirubin values with signs of cirrhosis, the dilemma exists when HBV DNA and liver function (such as ALT, AST, TBIL) remains low level. Whether antiviral therapy make sense or not in these patients with no signs of hepatitis or high viral replication remains unclear, especially for the relatively advanced stage HCC patients receiving TACE. Thus, the investigators carried out this prospective control study to compare the survivals for patients after TACE between with or without antiviral therapy.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• overall survival

  1 year

Secondary Outcomes (1)

• HBV reactivation

  1 year

Other Outcomes (1)

• HBV resistance to lamivudine or entecavir

  1 year

Study Arms (2)

Anti-viral treatment

EXPERIMENTAL

Oral antiviral drugs will be commenced after TACE. That is: Lamivudine 100mg once daily; or Entecavir 0.5mg once daily.

Drug: Lamivudine 100mg once daily; or Entecavir 0.5mg once daily.

Control

NO INTERVENTION

No anti-viral therapy after TACE.

Interventions

Lamivudine 100mg once daily; or Entecavir 0.5mg once daily. DRUG

In experimental group, Lamivudine 100mg once daily; or Entecavir 0.5mg once daily will be commenced after TACE.

Also known as: lamivudine 100 mg tablets (GlaxoSmithKline);, Entecavir 0.5mg tablets (Bristol-Myers Squibb)

Anti-viral treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients from 18 to 75 years of age with a diagnosis of HCC. A diagnosis of HCC based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL).
• The patient has not been previously treated with surgery, radiation therapy, radiofrequency ablation, percutaneous ethanol or acetic acid injection, or cryoablation, or any other treatment with chemotherapeutic agents or sorafenib.
• The patient has not been previously treated with any anti-viral agents, including interferon or nucleosides analogs (NAs).
• Adults patients with a diagnosis of HCC which is not amenable to surgical resection ,local ablative therapy or any other radically cured treatment.
• The MDT group of HCC agree to administer TACE in this patient.
• Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria.
• No serious concurrent medical illness.
• Unresectable TNM stage Ⅲ or Ⅳ disease.
• Zubrod-ECOG-WHO performance status: 0 or 1. and the estimated survival more than 4 months.
• Not pregnant or breast-feeding patients
• No significant renal impairment (creatinine clearance \< 30 mL/minute) or patients on dialysis
• No current infections requiring antibiotic therapy
• Not on anticoagulation or suffering from a known bleeding disorder
• No unstable coronary artery disease or recent MI
• Ability to understand the protocol and to agree to and sign a written informed consent document

You may not qualify if:

• \- History of HIV or HCV infection.
• History of organ allograft
• Known or suspected allergy to the investigational agents or any agent given in association with this trial.
• Evidence of bleeding diathesis.
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
• Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 4 weeks of study entry.
• Serious non-healing wound, ulcer, or bone fracture
• Known central nervous system tumors including metastatic brain disease
• Any event \> grade 2 National Cancer Institute \[NCI\]-Common Terminology Criteria for Adverse Events \[CTCAE\] version 3.0
• Severe complication after TACE.
• History of hepatotoxic medication within 8 wk prior to the current treatment.
• History of corticosteroid administration.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (12)

• Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen CJ; Taiwan Community-Based Cancer Screening Project Group. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002 Jul 18;347(3):168-74. doi: 10.1056/NEJMoa013215.

  PMID: 12124405 BACKGROUND

• de Franchis R, Hadengue A, Lau G, Lavanchy D, Lok A, McIntyre N, Mele A, Paumgartner G, Pietrangelo A, Rodes J, Rosenberg W, Valla D; EASL Jury. EASL International Consensus Conference on Hepatitis B. 13-14 September, 2002 Geneva, Switzerland. Consensus statement (long version). J Hepatol. 2003;39 Suppl 1:S3-25. No abstract available.

  PMID: 14708673 BACKGROUND

• Ho J, Wu PC, Kung TM. An autopsy study of hepatocellular carcinoma in Hong Kong. Pathology. 1981 Jul;13(3):409-16. doi: 10.3109/00313028109059059.

  PMID: 6272177 BACKGROUND

• Lok AS, Lai CL, Wu PC, Wong VC, Yeoh EK, Lin HJ. Hepatitis B virus infection in Chinese families in Hong Kong. Am J Epidemiol. 1987 Sep;126(3):492-9. doi: 10.1093/oxfordjournals.aje.a114681.

  PMID: 3618581 BACKGROUND

• Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73. doi: 10.1001/jama.295.1.65.

  PMID: 16391218 BACKGROUND

• Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004 Oct 7;351(15):1521-31. doi: 10.1056/NEJMoa033364.

  PMID: 15470215 BACKGROUND

• Shuqun C, Mengchao W, Han C, Feng S, Jiahe Y, Wenming C, Zhengfeng Y, Yuxiang Z, Peijun W. Antiviral therapy using lamivudine and thymosin alpha1 for hepatocellular carcinoma coexisting with chronic hepatitis B infection. Hepatogastroenterology. 2006 Mar-Apr;53(68):249-52.

  PMID: 16608033 BACKGROUND

• Jang JW, Choi JY, Bae SH, Yoon SK, Chang UI, Kim CW, Cho SH, Han JY, Lee YS. A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization. Hepatology. 2006 Feb;43(2):233-40. doi: 10.1002/hep.21024.

  PMID: 16440357 BACKGROUND

• Piao CY, Fujioka S, Iwasaki Y, Fujio K, Kaneyoshi T, Araki Y, Hashimoto K, Senoh T, Terada R, Nishida T, Kobashi H, Sakaguchi K, Shiratori Y. Lamivudine treatment in patients with HBV-related hepatocellular carcinoma--using an untreated, matched control cohort. Acta Med Okayama. 2005 Oct;59(5):217-24. doi: 10.18926/AMO/31969.

  PMID: 16286955 BACKGROUND

• Lao XM, Wang D, Shi M, Liu G, Li S, Guo R, Yuan Y, Chen M, Li J, Zhang Y, Lin X. Changes in hepatitis B virus DNA levels and liver function after transcatheter arterial chemoembolization of hepatocellular carcinoma. Hepatol Res. 2011 Jun;41(6):553-63. doi: 10.1111/j.1872-034X.2011.00796.x. Epub 2011 Mar 29.

  PMID: 21615643 BACKGROUND

• Lao XM, Luo G, Ye LT, Luo C, Shi M, Wang D, Guo R, Chen M, Li S, Lin X, Yuan Y. Effects of antiviral therapy on hepatitis B virus reactivation and liver function after resection or chemoembolization for hepatocellular carcinoma. Liver Int. 2013 Apr;33(4):595-604. doi: 10.1111/liv.12112. Epub 2013 Feb 13.

  PMID: 23402625 BACKGROUND

• Lao XM, Xia HH, Lin XJ, Li SP. Antiviral therapy in patients with hepatitis B virus-related hepatocellular carcinoma: is it ready for universal application? J Viral Hepat. 2013 Dec;20(12):e148-9. doi: 10.1111/jvh.12147. Epub 2013 Jul 17. No abstract available.

  PMID: 24304460 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Lamivudine; entecavir; halofantrine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• Xiao-Jun Lin, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

• Xiang-Ming Lao, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiang-Ming Lao, MD

CONTACT

8620-87343114; laoxming@mail.sysu.edu.cn

Xiao-Jun Lin, MD

CONTACT

8620-87343017; linxj@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 3, 2013
• First Posted: July 10, 2013
• Study Start: July 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2016
• Last Updated: July 23, 2013

Record last verified: 2013-07

Locations

CN (1)