This phase III trial studies the effect of hepatitis B antiviral (anti-HBV) therapy in preventing liver complications in patients with chronic or past hepatitis B virus (HBV) who are receiving anti-cancer therapy for solid tumors. People with chronic or past HBV who are undergoing therapy for cancer are at an increased risk for changes in the liver which could be minor or severe. Anti-HBV therapy acts against infections caused by HBV and may help reduce the chance that HBV gets worse or comes back in patients receiving anti-cancer therapy for solid tumors.
Co-Primary Objectives 1. To compare the effect of prophylactic anti-HBV therapy versus upon indication anti-HBV therapy on time-to-adverse liver outcomes of liver failure or liver-related death in patients with chronic HBV infection (HBsAg+ and anti-HBc+) receiving anti-cancer therapy for solid tumors. 2. To compare the effect of upon indication anti-HBV therapy versus usual care on time-to-adverse liver outcomes of liver failure or liver-related death in patients with past HBV infection (HBsAg- and anti-HBc+) receiving anti-cancer therapy for solid tumors. Secondary Objectives 1. Using time-to-event analysis, to compare the effect of anti-HBV therapy versus upon indication anti-HBV therapy on HBV reactivation, on the combined endpoint of adverse liver outcomes (liver failure or liver-related death) and HBV reactivation, and on HBV flare by arm in patients with chronic HBV infection receiving anticancer therapy for solid tumors. 2. Using time-to-event analysis, to compare the effect of upon indication anti-HBV therapy versus usual care on HBV reactivation, on the combined endpoint of adverse liver outcomes (liver failure or liver-related death) and HBV reactivation, and on HBV flare by arm in patients with past HBV infection receiving anti-cancer therapy for solid tumors. Translational Objectives 1. To compare baseline and changes in overall immune status and HBV-specific immune response in patients with solid tumors and chronic or past HBV infection receiving anti-cancer therapy, and to compare the differences in these immune responses by HBV reactivation status. 2. To identify demographic and clinical predictors and correlative immunologic biomarkers of HBV reactivation after receipt of anti-cancer therapy in patients with solid tumors and chronic or past HBV infection. OUTLINE: Patients are recruited in two cohorts (Cohort 1: chronic HBV infection, Cohort 2: past HBV infection), with each cohort randomized equally to one of two potential treatment arms. Chronic HBV Infection (Cohort 1) Arms: Arm 1: Patients receive tenofovir alafenamide (TAF) orally (PO) once daily (QD) or tenofovir disoproxil fumarate (TDF) PO QD or entecavir PO QD immediately or within 42 days after initial dose of chemotherapy. Treatment continues for up to 6 months after the last dose of chemotherapy or a maximum of 24 months in the absence of disease progression or unacceptable toxicity. Arm 2: Patients receive TAF PO QD or TDF PO QD or entecavir PO QD after HBV reactivation during chemotherapy. Treatment continues for up to 6 months after the last dose of chemotherapy or a maximum of 24 months in the absence of disease progression or unacceptable toxicity. Past HBV infection (Cohort 2) Arms: Arm 3: Patients receive TAF PO QD or TDF PO QD or entecavir PO QD after HBV reactivation during chemotherapy. Treatment continues for up to 6 months after the last dose of chemotherapy or a maximum of 24 months in the absence of disease progression or unacceptable toxicity. Arm 4: Patients receive anti-HBV therapy at the discretion of the physician. Any Food and Drug Administration (FDA) approved anti-viral medication for HBV may be used. (Cohort 1: Arm 2 and Cohort 2: Arm 3 follow the same treatment plan, but are considered part of separate parallel studies and are therefore identified as separate arms.) Patients are followed for 24 months: every 4 weeks from randomization to week 24, then every 8 weeks thereafter up to week 104.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Enrollment
4
Mercy Hospital Fort Smith
Fort Smith, Arkansas, United States
Kaiser Permanente-Anaheim
Anaheim, California, United States
Kaiser Permanente-Deer Valley Medical Center
Antioch, California, United States
Kaiser Permanente-Baldwin Park
Baldwin Park, California, United States
Kaiser Permanente-Bellflower
Bellflower, California, United States
Number of Participants With Adverse Liver Outcome
Adverse liver outcome: Defined as liver-related death or liver failure (ascites, hepatic encephalopathy or impaired hepatic synthetic function defined as total bilirubin ≥ 5 mg/dL or INR ≥ 2.0) not due to disease progression in the liver. Assessment of the primary endpoint will be made by sites and subsequently adjudicated by the research oversight team by blinded review.
Time frame: From randomization to 24 months
Number of Participants With Hepatitis B Virus (HBV) Reactivation
HBV reactivation is is defined as one of the following: * ≥ 2 log (100-fold) increase in HBV DNA compared to baseline in patients with detectable HBV DNA at baseline, or * HBV DNA ≥ 3 log (1,000) IU/mL in a patient with previously undetectable HBV DNA, or * HBV DNA ≥ 4 log (10,000) IU/mL if baseline HBV DNA not available, or * HBsAg seroreversion (HBsAg- to HBsAg+) in a patient previously HBsAg-.
Time frame: From randomization up to 24 months
Number of Participants With Hepatitis B Virus (HBV) Flare
Hepatitis flare is defined as ALT \> 3 x baseline and \>100 U/L.
Time frame: From randomization to 24 months
Combined Endpoint of Adverse Liver Outcomes and HBV Reactivation, Number of Participants
Adverse liver outcome: Defined as liver-related death or liver failure (ascites, hepatic encephalopathy or impaired hepatic synthetic function defined as total bilirubin ≥ 5 mg/dL or INR ≥ 2.0) not due to disease progression in the liver. Assessment of the primary endpoint will be made by sites and subsequently adjudicated by the research oversight team by blinded review. HBV reactivation is defined as one of the following: * ≥ 2 log (100-fold) increase in HBV DNA compared to baseline in patients with detectable HBV DNA at baseline, or * HBV DNA ≥ 3 log (1,000) IU/mL in a patient with previously undetectable HBV DNA, or * HBV DNA ≥ 4 log (10,000) IU/mL if baseline HBV DNA not available, or * HBsAg seroreversion (HBsAg- to HBsAg+) in a patient previously HBsAg-. The combined endpoint of adverse liver outcomes and HBV reactivation is the occurrence of either adverse liver outcome or HBV reactivation as defined above.
Time frame: From randomization to 24 months
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