Immune Checkpoint Therapy vs Target Therapy in Reducing Serum HBsAg Levels in Patients With HBsAg+ Advanced Stage HCC

Sponsor
Humanity & Health Medical Group Limited
Study ID
NCT03899428
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Durvalumab — DRUG
    Durvalumab 1500 mg IV (intravenous infusion)
  • Sorafenib — DRUG
    Prescribed by physician.
  • Lenvatinib — DRUG
    Prescribed by physician.
  • Regorafenib — DRUG
    Prescribed by physician.
  • Cabozantinib — DRUG
    Prescribed by physician.

Study Details

It is estimated that over 50% of HCC cases worldwide are related to chronic HBV. There are approximately 350-400 million people across the world infected with HBV, the majority reside in or originate from Asia. Each year HBV accounts for 749,000 new cases of HCC and 692,000 HCC-related deaths. The annual incidence of HCC is estimated to be \<1% for non-cirrhotic HBV infected patients and 2-3% for those with cirrhosis. While the most approved nucleos(t)ide analogues (NA) suppress HBV replication through inhibition of HBV-DNA polymerase and are reported to reduce the risk of HCC incidence, however, such risk is not completely eliminated under NA treatment. The recent availability of commercial quantitative assays of serum hepatitis B surface antigen (HBsAg) has enabled quantitative HBsAg to be used as a biomarker for prognosis and treatment response in CHB. It has been suggested that HBsAg decline during lamivudine or entecavir therapy is slower and less pronounced compared to interferon treatment, despite a higher effect on HBV DNA suppression. Based on HBsAg kinetics, it has been estimated that the predicted median time to HBsAg loss in patients treated with lamivudine or entecavir is more than 30 years. Thus, treatment that can induce rapid decline of HBsAg would have clear advantage in reducing the treatment duration required to achieve HBsAg-loss. Interestingly, in a recent preliminary study, 12-weeks of treatment with nivolumab has showed the modest effect on HBsAg decline in HBeAg negative CHB patients. Thus, in this clinical trial, the investigator will investigate whether immune checkpoint therapy is more effective in inducing HBsAg decline compared with target therapy in HBsAg-positive patients with advanced stage HCC.

Key Dates

Start date
May 2, 2019
Status verified
Mar 2025
Primary completion
Dec 31, 2025
Completion
Dec 31, 2025

Study Design

Enrollment
30 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Immune Checkpoint Therapy
    The subjects will receive durvalumab 1500 mg Q4W
  • Experimental: Target Therapy
    The subjects will receive tyrosine kinase inhibitors, including sorafenib, lenvatinib, regorafenib, or cabozantinib, daily

Primary Outcome Measure

Time to decline to ≥ 2 log10 IU/mL of serum HBsAg [ Time Frame: Assessed up to 2 years ]

Central Contacts

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