Durvalumab for Advanced Hepatocellular Carcinoma in Patients With Active Chronic Hepatitis B Virus Infection

NCT04294498 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 201910075MIPD
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

PD1 blockade has been approved as salvage therapy for advanced hepatocellular carcinoma (HCC). Although there is not solid evidence that PD1 blockade would induce hepatitis B virus (HBV) reactivation, previous clinical trials of PD1 blockade required enrolled patients to receive anti-HBV medications and control the viral load to be under 100-2000 IU/mL before initiation of PD1 blockade therapy. Such a requirement may not be necessary and could delay the treatment. Guidelines for prevention of chemotherapy induced HBV reactivation only suggest combining anti-HBV medications during the chemotherapy course without such a requirement of very load HBV viral load. The investigators hypothesized that under anti-HBV medications, patients with advanced HCC and active chronic hepatitis B virus (HBV) infection can receive durvalumab treatment without increased risks of HBV reactivation and related complications.

Conditions

Advanced Hepatocellular Carcinoma

Keywords

Checkpoint inhibitor; Hepatocellular carcinoma; Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• The rate of HBV reactivation during durvalumab treatment

  To assess the rate of HBV reactivation during durvalumab treatment, defined as a ≥2 log (100-fold) increase in serum HBV DNA compared to the baseline level.

  30 months

Secondary Outcomes (7)

• The rate of hepatitis flare during durvalumab treatment

  30 months

• To assess the rate of HBV-associated hepatitis during durvalumab treatment.

  30 months

• To assess the efficacy of durvalumab treatment

  30 months

• To assess the efficacy of durvalumab treatment

  30 months

• To assess the efficacy of durvalumab treatment

  30 months

Study Arms (1)

Durvalumab

EXPERIMENTAL

Durvalumab

Drug: Durvalumab

Interventions

Durvalumab DRUG

Entecavir treatment for chronic hepatitis B will be started within one week before initiation of durvalumab treatment for advanced hepatocellulcar carcinoma

Also known as: Entecavir

Durvalumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Histologically or clinically (typical HCC imaging findings by multi-phase CT or MRI) diagnosed HCC.
• Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy.
• HBeAg (-) active chronic HBV infection, defined by positive serum HBsAg AND serum HBV DNA ≥ 2,000 IU/mL.
• No previous immune checkpoint inhibitor treatment
• The patient refuses, has disease progression on, or does not tolerate treatment kinase inhibitors such as sorafenib or lenvatinib
• Age \> 20 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Child-Pugh class A
• ≥1 measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
• Body weight \>30 kg
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1.0 x 109/L (\> 1,000 per mm3)
• Platelet count ≥75 x 109/L (\>75,000 per mm3)

You may not qualify if:

• Serum HBeAg (+)
• Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
• Active or prior documented GI variceal bleed or history of upper GI bleeding, ulcers, or esophageal varices with bleeding within 12 months; adequate endoscopic therapy according to institutional standards is required for patients with history of esophageal variceal bleeding or assessed as high risk for esophageal variceal by the treating investigator.
• Previous organ transplants
• Participation in another clinical study with an investigational product during the last 2 weeks
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤14 days prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by the principal investigator
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study treatment.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]).
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection (except HBV infection), symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• Ministry of Science and Technology, Taiwan: collaborator
• AstraZeneca: collaborator

Study Sites (1)

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Related Publications (1)

• Shao YY, Chen CT, Chuang CH, Su TH, Ho MC, Tseng TC, Liu TH, Wu TC, Cheng AL, Hsu CH. Prompt initiation of durvalumab and tremelimumab for unresectable hepatocellular carcinoma in patients with chronic active hepatitis B: a phase 2 clinical trial. Br J Cancer. 2025 May;132(9):822-827. doi: 10.1038/s41416-025-02978-7. Epub 2025 Mar 24.

  PMID: 40128285 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Hepatitis B, Chronic

Interventions

durvalumab; entecavir

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2020
• First Posted: March 4, 2020
• Study Start: November 2, 2020
• Primary Completion: September 1, 2024
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 26, 2025

Record last verified: 2025-03

Locations

TW (1)