Prophylactic or Preemptive Entecavir in Patients With Gastrointestinal Cancer Who Are Inactive Hepatitis B Carriers

Official title

An Open, Multicentre, Phase 3, Randomized Controlled Clinical Trial to Compare the Prophylactic Use or Preemptive Use of an Anti-viral Drug Entecavir in Patients With Gastrointestinal Cancer Who Are Inactive Hepatitis B Carriers

Overview

There has been no report on whether the patients with gastrointestinal cancer who are also inactive hepatitis B carriers should receive prophylactic use or preemptive use of an anti-viral drug entecavir during anti-tumor therapy. This open, multicentre, phase 3, randomized controlled clinical trial aims to compare the impact of the prophylactic use or preemptive use of an anti-viral drug entecavir on the outcomes of patients with gastrointestinal cancer who are also inactive hepatitis B carriers during chemotherapy or immunotherapy and the subsequent follow-ups, including two cohorts of chemotherapy and immunotherapy.

Detailed description

Patients with gastrointestinal cancer who are also inactive hepatitis B carriers are enrolled and randomized into two groups as following. Patients in experimental group are treated with entecavir prophylactically in the dose of 0.5mg p.o. every day from the initiation of chemotherapy or immunotherapy till 6 months after the end of chemotherapy or immunotherapy. Patients in active comparator group are only treated with entecavir in the dose of 0.5mg p.o. every day from the time that the DNA copies of hepatitis B virus become positive till 6 months after the end of chemotherapy or immunotherapy.

Interventions

• Drug Entecavir
  anti hepatitis B virus

Primary outcome measures

• The incidence of hepatitis B virus reactivation [Time frame: through study completion, an average of 1 year]

Secondary outcome measures (6)

• Hepatitis [Time frame: through study completion, an average of 1 year]
• Hepatitis B virus associated hepatitis [Time frame: through study completion, an average of 1 year]
• Interruption of chemotherapy/immunotherapy due to hepatitis [Time frame: through study completion, an average of 1 year]
• Severe HBV associated hepatitis [Time frame: through study completion, an average of 1 year]
• HBV associated acute liver failure [Time frame: through study completion, an average of 1 year]
• HBV related death [Time frame: through study completion, an average of 1 year]

Eligibility criteria

Inclusion criteria

• Patients with age between 18 and 75
• Patient with histology-proven locally advanced unresectable or metastatic gastrointestinal cancers (colorectal cancer, gastric cancer, esophageal cancer, hepatocellular carcinoma, pancreatic cancer, and cholangiocarcinoma)
• Planned to receive first-, second-, or third-line anti-tumor therapy (chemotherapy or PD-1/PD-L1 monoclonal antibody immunotherapy)
• Patients with Eastern Cooperative Oncology Group performance status (ECOG) of 0-2
• Patients planned for at least 4 cycles of chemotherapy or immunotherapy
• Patients with at least 6 months' life expectancy from date of recruitment
• Patients with chronic or past HBV infection (HBsAg-positive or HBcAb-positive), and hepatitis B is inactive
• Patients with normal liver function tests including alanine aminotransferase (ALT), aspartate aminotransferase alkaline (AST), and bilirubin
• Patients with negative HBV-DNA
• Adequate major organ function (laboratory tests 14 days before randomization meeting requirements for anti-tumor therapy)
• Patients who sign the informed consent
• Patients with good compliance during chemotherapy and follow-ups.

Exclusion criteria

• History of liver cirrhosis
• Prior HBV reactivation
• Received anti-HBV therapy for chronic hepatitis B within 6 months before enrollment
• Active co-infection with other hepatitis viruses
• HIV infection
• Autoimmune hepatitis
• History of hepatic radiotherapy
• Scheduled hepatic radiotherapy or radioisotope therapy
• Pregnant or lactating women
• Patients with a history of psychiatric drugs abuse and can't quit or with a mental disorder
• Patients with immunodeficiency, other congenital or acquired immunodeficiency, or transplantation history
• According to the investigators' judgment, patients with concomitant disease that seriously harms patients' safety or the completion of study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Publications

• Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015 Jan;148(1):221-244.e3. doi: 10.1053/j.gastro.2014.10.038. Epub 2014 Oct 31. No abstract available. PMID 25447852
• Huang H, Li X, Zhu J, Ye S, Zhang H, Wang W, Wu X, Peng J, Xu B, Lin Y, Cao Y, Li H, Lin S, Liu Q, Lin T. Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA. 2014 Dec 17;312(23):2521-30. doi: 10.1001/jama.2014.15704. PMID 25514302

Identifiers

NCT: NCT06966232 · GIC-HBV

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗