Advanced Hepatocellular CarcinomaPhase 2NCT04294498
Durvalumab for Advanced Hepatocellular Carcinoma in Patients With Active Chronic Hepatitis B Virus Infection
A Phase 2 study testing Durvalumab in people with Advanced Hepatocellular Carcinoma, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Advanced Hepatocellular Carcinoma
- What is being tested?
- Durvalumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteTaiwan
- Study dates
- 2 Nov 2020to 29 Jun 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 21Show fewer
- 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)
- Serum bilirubin ≤2 x institutional upper limit of normal (ULN).
- AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless active liver malignancies are present, in which case it must be ≤5x ULN
- Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Must have a life expectancy of at least 12 weeks
Who cannot join
- 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
Show all 25Show fewer
- 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 unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- 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
- History of leptomeningeal carcinomatosis
- Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry
- History of active primary immunodeficiency or HIV infection
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), and hepatitis C
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
- Prior randomisation or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study of Durvalumab (MEDI 4736) for Advanced Hepatocellular Carcinoma in Patients With Active Chronic Hepatitis B Virus Infection
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.
Read the detailed description
Although durvalumab has not been approved as treatment for HCC, similar PD1 blockade agents such as nivolumab and pembrolizumab have gain approval as salvage therapy for advanced HCC. The investigators will enroll 43 patients with active (defined as serum viral load > 2000 IU/mL) chronic HBV infection (defined as positive serum HBV surface antigen). All patients would receive entecavir within 7 days of initiation of durvalumab treatment. Durvalumab 1500 mg would be given intravenously every 4 weeks until confirmed disease progression, intolerable side effects, or completion of 24 treatment. Tumor assessment will be performed every 8-12 weeks. HBV viral load will be monitored at least once per month. Entecavir treatment will be continued at least 6 months after discontinuation of durvalumab treatment.
- Conditions
- Advanced Hepatocellular Carcinoma
- Being tested
- Durvalumab
- Keywords
- Checkpoint inhibitor, Hepatocellular carcinoma, Chronic Hepatitis B
- Medical subject headings
- Carcinoma, Hepatocellular, Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called Entecavir
Entecavir treatment for chronic hepatitis B will be started within one week before initiation of durvalumab treatment for advanced hepatocellulcar carcinoma
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab | Experimental | Durvalumab Receives: Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 months
Secondary outcomes (7)
The rate of hepatitis flare during durvalumab treatment
To assess the rate of hepatitis flare, defined as an ALT increase to ≥3 times the baseline level and >100 U/L, during durvalumab treatment.
Measured: 30 months
To assess the rate of HBV-associated hepatitis during durvalumab treatment.
To assess the rate of HBV-associated hepatitis, defined as HBV reactivation plus hepatitis flare, during durvalumab treatment.
Measured: 30 months
To assess the efficacy of durvalumab treatment
To assess the efficacy of durvalumab treatment, as determined by the objective tumor response rates per RECIST v1.1.
Measured: 30 months
To assess the efficacy of durvalumab treatment
To assess the efficacy of durvalumab treatment, as determined by time to tumor progression.
Measured: 30 months
To assess the efficacy of durvalumab treatment
To assess the efficacy of durvalumab treatment, as determined by progression-free survival.
Measured: 30 months
To assess the efficacy of durvalumab treatment
To assess the efficacy of durvalumab treatment, as determined by overall survival.
Measured: 30 months
To assess the adverse events during durvalumab treatment.
To assess the adverse events, defined by CTC-AE version 5.0, during durvalumab treatment.
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2020
- Study start2 Nov 2020
- Primary completion1 Sep 2024
- Study completion29 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Science and Technology, Taiwan, AstraZeneca
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04294498
- Sponsor's protocol ID
- 201910075MIPD
- Status last verified
- Jun 2026
- First submitted
- 25 Feb 2020
- Last updated
- 30 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 40128285
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Durvalumab (MEDI 4736) for Advanced Hepatocellular Carcinoma in Patients With Active Chronic Hepatitis B Virus Infection
- ClinicalTrials.gov ID
- NCT04294498
- Acronym / sponsor ID
- 201910075MIPD
- Conditions
- Advanced Hepatocellular Carcinoma
- Keywords
- Checkpoint inhibitor, Hepatocellular carcinoma, Chronic Hepatitis B
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- Ministry of Science and Technology, Taiwan, AstraZeneca
- Study start
- 2 Nov 2020 (actual)
- Primary completion
- 1 Sep 2024 (actual)
- Study completion
- 29 Jun 2026 (actual)
- First posted
- 4 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Although durvalumab has not been approved as treatment for HCC, similar PD1 blockade agents such as nivolumab and pembrolizumab have gain approval as salvage therapy for advanced HCC. The investigators will enroll 43 patients with active (defined as serum viral load > 2000 IU/mL) chronic HBV infection (defined as positive serum HBV surface antigen). All patients would receive entecavir within 7 days of initiation of durvalumab treatment. Durvalumab 1500 mg would be given intravenously every 4 weeks until confirmed disease progression, intolerable side effects, or completion of 24 treatment. Tumor assessment will be performed every 8-12 weeks. HBV viral load will be monitored at least once per month. Entecavir treatment will be continued at least 6 months after discontinuation of durvalumab treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Durvalumab | Experimental | Drug: DurvalumabDurvalumab |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurvalumabAlso: EntecavirEntecavir treatment for chronic hepatitis B will be started within one week before initiation of durvalumab treatment for advanced hepatocellulcar carcinoma | Drug | Durvalumab |
Primary outcome
The rate of HBV reactivation during durvalumab treatment
Time frame: 30 months
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.
7 secondary outcomes
The rate of hepatitis flare during durvalumab treatment
Time frame: 30 months
To assess the rate of HBV-associated hepatitis during durvalumab treatment.
Time frame: 30 months
To assess the efficacy of durvalumab treatment
Time frame: 30 months
To assess the efficacy of durvalumab treatment
Time frame: 30 months
To assess the efficacy of durvalumab treatment
Time frame: 30 months
To assess the efficacy of durvalumab treatment
Time frame: 30 months
To assess the adverse events during durvalumab treatment.
Time frame: 30 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2026.
- Derived from this study: PubMed 40128285Shao 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.
Related trials for Advanced Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Not yet recruitingPhase 2
A Clinical Study Evaluating the Safety and Efficacy of Ivonescimab as Second-line Treatment in Patients With Advanced Hepatocellular Carcinoma
Hepatocellular Carcinoma (HCC), HCC - Hepatocellular Carcinoma
Active, not recruitingPhase 2
Durvalumab and Tremelimumab in Combination With Propranolol and Chemotherapy for Treatment of Advanced Hepatopancreabiliary Tumors (BLOCKED)
Pancreatic Cancer, Hepatocellular Cancer
RecruitingPhase 1/2
A Phase 1 and 2 Study of VMD-102 in Hepatocellular Carcinoma and Other Solid Tumors
Hepatocellular Carcinoma (HCC), Metastatic Uveal Melanoma
Not yet recruitingPhase 2
Study Evaluating the Efficacy and Safety of BGB-B2033 in Participants With Advanced Hepatocellular Carcinoma
Hepatocellular Cancer, Liver Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Durvalumab in people with Advanced Hepatocellular Carcinoma, run by National Taiwan University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The rate of HBV reactivation during durvalumab treatment (time frame: 30 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04294498, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2026.