Gastrointestinal Cancers
Conditions
Keywords
Gastrointestinal Cancers, Entecavir, Hepatitis B Carrier, Chemotherapy, Immunotherapy
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.
Interventions
DRUGEntecavir
anti hepatitis B virus
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The incidence of hepatitis B virus reactivation | through study completion, an average of 1 year | HBV reactivation is defined as (1) an increase in HBV-DNA levels by ≥2 log10 (100-fold) compared to baseline or conversion from negative serum HBV-DNA to positive HBV-DNA; (2) if baseline HBV-DNA was undetectable, achieving HBV-DNA levels ≥3 log10 (1,000 IU/mL); or (3) if baseline levels were unknown or unavailable, reaching HBV-DNA levels ≥4 log10 (10,000 IU/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hepatitis B virus associated hepatitis | through study completion, an average of 1 year | Hepatitis B virus associated hepatitis is defined as hepatitis B virus (HBV) reactivation occurring prior to or concurrent with hepatitis during or following chemotherapy/immunotherapy , in the absence of clinical or laboratory evidence of acute infection by other hepatitis viruses or systemic diseases. |
| Interruption of chemotherapy/immunotherapy due to hepatitis | through study completion, an average of 1 year | Chemotherapy/immunotherapy disruption due to hepatitis is defined as either premature termination or a delay of at least 7 days between therapy cycles due to hepatitis . |
| Hepatitis | through study completion, an average of 1 year | Hepatitis is defined as a 3-fold or greater increase in the serum ALT level that exceeded the reference range or an absolute increase in the level of ALT of greater than 100 U/L compared with the baseline level |
| HBV associated acute liver failure | through study completion, an average of 1 year | HBV associated acute liver failure, also termed HBV associated fulminant hepatic failure , is defined as acute hepatic decompensation linked to HBV reactivation or acute exacerbation of HBV infection. It manifests within days to weeks, leading to severe complications such as coagulopathy, hepatic encephalopathy, and multiorgan failure, with a high 28-day mortality rate . Delayed initiation of nucleotide analogues may contribute to rapid disease progression and poor prognosis. |
| HBV related death | through study completion, an average of 1 year | HBV related death is defined as mortality directly attributable to HBV reactivation |
| Severe HBV associated hepatitis | through study completion, an average of 1 year | Severe HBV associated hepatitis is defined as grade 3 or higher HBV associated hepatitis according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
Countries
China
Contacts
Primary ContactXu Rui-hua, M.D. Ph.D
Backup ContactWang Feng, M.D. Ph.D
Outcome results
None listed