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

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

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.

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.

Inclusion Criteria:

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

Exclusion Criteria:

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