Clinical trial NCT06966232: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Gastrointestinal Cancers
Keywords: Gastrointestinal Cancers
Entecavir
Hepatitis B Carrier
Chemotherapy
Immunotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2025-05-11
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The incidence of hepatitis B virus reactivation
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Hepatitis
timeFrame: through study completion, an average of 1 year
measure: Hepatitis B virus associated hepatitis
timeFrame: through study completion, an average of 1 year
measure: Interruption of chemotherapy/immunotherapy due to hepatitis
timeFrame: through study completion, an average of 1 year
measure: Severe HBV associated hepatitis
timeFrame: through study completion, an average of 1 year
measure: HBV associated acute liver failure
timeFrame: through study completion, an average of 1 year
measure: HBV related death
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Xu Rui-hua, M.D. Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.