Hepatocellular CarcinomaPhase 2NCT03899428
Immune Checkpoint Therapy vs Target Therapy in Reducing Serum HBsAg Levels in Patients With HBsAg+ Advanced Stage HCC
A Phase 2 study testing Durvalumab, Sorafenib and Lenvatinib in people with Hepatocellular Carcinoma, run by Humanity & Health Medical Group Limited at 1 site in Hong Kong.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Durvalumab, Sorafenib and Lenvatinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteHong Kong
- Study dates
- 2 May 2019to 31 Dec 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HBsAg positive with serum HBsAg levels ≥ 2 log IU/ml
- Age ≥ 18 years old on the day of consent
- Capable of understanding and complying with the protocol requirements and signed informed consent
- Documented histological or cytological diagnosis of HCC within 1 year
- Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C
- Child-Pugh Score class A or B
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- ECOG performance status of 0 or 1 at enrollment.
- Treated with either entecavir or tenofovir or TAF before initiation of anti-PDL1 or TKI
- At least 1 measurable lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. A lesion which progressed after previous ablation or TACE could be measurable if it meets these criteria
- Adequate organ and marrow function, as defined below. Criteria "a," "b," "c," and "f" cannot be met with transfusions, infusions, or growth factor support administered within 14 days of starting the first dose.
- Hemoglobin ≥9 g/dL
- Absolute neutrophil count ≥1000/μL
- Platelet count ≥75000/μL
- Total bilirubin (TBL) ≤2.0× upper limit of normal (ULN)
- AST and ALT ≤5×ULN
- Albumin ≥2.8 g/dL
- International normalized ratio (INR) ≤1.6
- Calculated creatinine clearance ≥50 mL/minute as determined by Cockcroft-Gault (using actual body weight) or 24-hour urine creatinine clearance
Who cannot join
- Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
- Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment (eg, I-131 or Y-90) within 6 weeks of starting treatment. Subject is excluded if there are any clinically relevant ongoing complications from prior radiation therapy
- Prior interferon treatment
- Concomitant anticoagulation, at therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, low molecular weight heparin (LMWH), thrombin or coagulation factor X (FXa) inhibitors, or antiplatelet agents (eg, clopidogrel). Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (≤ 1 mg/day), and low-dose LMWH are permitted.
- The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
- Cardiovascular disorders including i. Symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias ii. Uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment iii. Stroke (including TIA), myocardial infarction, or other ischemic event within 6 months before starting treatment iv. Thromboembolic event within 3 months before starting treatment. Subjects with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumor are eligible b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before starting treatment, Note: Complete healing of an intra-abdominal abscess must be confirmed prior to starting treatment c. Major surgery within 2 months before starting treatment. Complete healing from major surgery must have occurred 1 month before starting treatment. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at least 7 days before starting treatment. Subjects with clinically relevant complications from prior surgery are not eligible d. Cavitating pulmonary lesion(s) or endobronchial disease e. Lesion invading a major blood vessel (eg, pulmonary artery or aorta) f. Clinically significant bleeding risk including the following within 3 months of starting treatment: hematuria, hematemesis, hemoptysis of >0.5 teaspoon (>2.5 mL) of red blood, or other signs indicative of pulmonary hemorrhage, or history of other significant bleeding if not due to reversible external factors g. Other clinically significant disorders such as: i. known infection with human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)-related illness requiring systemic treatment ii. Serious non-healing wound/ulcer/bone fracture iii. Malabsorption syndrome iv. Uncompensated/symptomatic hypothyroidism v. Requirement for hemodialysis or peritoneal dialysis
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- Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding are excluded with the following clarification: subjects with history of prior variceal bleeding must have been treated with adequate endoscopic therapy without any evidence of recurrent bleeding for at least 6 months prior to study entry and must be stable on optimal medical management (e.g. non-selective beta blocker, proton pump inhibitor) at study entry.
- Moderate or severe ascites
- Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 7 days before starting treatment Note: If the QTcF is > 500 ms in first ECG, a total of 3 ECGs should be performed. If the average of these 3 consecutive results for QTcF is ≤ 500 ms, the subject meets eligibility in this regard.
- Inability to swallow tablets
- Previously identified allergy or hypersensitivity to components of the study treatment formulations
- Pregnant or lactating females
- Diagnosis of another malignancy within 2 years before starting treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hong Kong1 site, 1 recruiting
- Recruiting
Humanity & Health Research Centre
Hong Kong, Hong Kong SAR
Danny Wang, 852-28613777, danny.wang@hnhmgl.com
About this study
Official title: A Randomized, Open-label Trial Comparing Immune Checkpoint Therapy vs Target Therapy in Reducing Serum HBsAg Levels in Patients With HBeAg-positive Advanced Stage Hepatocellular Carcinoma (VICI-5)
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.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Durvalumab, Sorafenib, Lenvatinib, Regorafenib, Cabozantinib
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called IMFINZI®
Durvalumab 1500 mg IV (intravenous infusion)
SorafenibDrug
Also called Nexavar, BAY43-9006
Prescribed by physician.
LenvatinibDrug
Also called Lenvima, E7080
Prescribed by physician.
RegorafenibDrug
Also called Stivarga, BAY73-4506
Prescribed by physician.
CabozantinibDrug
Also called Cabometyx, XL184
Prescribed by physician.
| Study group | Role | What they receive |
|---|---|---|
| Immune Checkpoint Therapy | Experimental | The subjects will receive durvalumab 1500 mg Q4W Receives: Drug: Durvalumab |
| Target Therapy | Experimental | The subjects will receive tyrosine kinase inhibitors, including sorafenib, lenvatinib, regorafenib, or cabozantinib, daily Receives: Drug: Sorafenib; Drug: Lenvatinib; Drug: Regorafenib; Drug: Cabozantinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to decline to ≥ 2 log10 IU/mL of serum HBsAg
Measured: Assessed up to 2 years
Secondary outcomes (6)
Time to loss of serum HBsAg
Measured: Assessed up to 2 years
Time to development of anti-HBsAg
Measured: Assessed up to 2 years
Progression-free survival (PFS) per RECIST 1.1
Measured: From date of starting treatment until the date of objective disease progression or death, assessed up to 2 years.
Objective response rate (ORR) per RECIST 1.1
Measured: From date of starting treatment until the date of objective disease progression or death, assessed up to 2 years.
Overall survival (OS)
Measured: From the date of starting treatment until death due to any cause, assessed up to 2 years.
Adverse events assessed in terms of seriousness, severity, and relationship to the study material according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Measured: From the time of signature of informed consent, throughout the treatment period, and up to the follow-up period, assessed up to 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2019
- Study start2 May 2019
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Humanity & Health Medical Group Limited
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- George Lau, PhD, Principal investigator, Humanity & Health Research Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03899428
- Sponsor's protocol ID
- VICI-5
- Status last verified
- Mar 2025
- First submitted
- 26 Mar 2019
- Last updated
- 24 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label Trial Comparing Immune Checkpoint Therapy vs Target Therapy in Reducing Serum HBsAg Levels in Patients With HBeAg-positive Advanced Stage Hepatocellular Carcinoma (VICI-5)
- ClinicalTrials.gov ID
- NCT03899428
- Acronym / sponsor ID
- VICI-5
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Humanity & Health Medical Group LimitedUniversity, hospital or other
- Study start
- 2 May 2019 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 2 Apr 2019 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immune Checkpoint Therapy | Experimental | Drug: DurvalumabThe subjects will receive durvalumab 1500 mg Q4W |
| Target Therapy | Experimental | Drug: Sorafenib, Drug: Lenvatinib, Drug: Regorafenib, Drug: CabozantinibThe subjects will receive tyrosine kinase inhibitors, including sorafenib, lenvatinib, regorafenib, or cabozantinib, daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- HBsAg positive with serum HBsAg levels ≥ 2 log IU/ml
- Age ≥ 18 years old on the day of consent
- Capable of understanding and complying with the protocol requirements and signed informed consent
- Documented histological or cytological diagnosis of HCC within 1 year
- Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C
Key exclusion criteria (13 listed)
- Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
- Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment (eg, I-131 or Y-90) within 6 weeks of starting treatment. Subject is excluded if there are any clinically relevant ongoing complications from prior radiation therapy
- Prior interferon treatment
- Concomitant anticoagulation, at therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, low molecular weight heparin (LMWH), thrombin or coagulation factor X (FXa) inhibitors, or antiplatelet agents (eg, clopidogrel). Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (≤ 1 mg/day), and low-dose LMWH are permitted.
- The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
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: IMFINZI®Durvalumab 1500 mg IV (intravenous infusion) | Drug | Immune Checkpoint Therapy |
| SorafenibAlso: Nexavar, BAY43-9006Prescribed by physician. | Drug | Target Therapy |
| LenvatinibAlso: Lenvima, E7080Prescribed by physician. | Drug | Target Therapy |
| RegorafenibAlso: Stivarga, BAY73-4506Prescribed by physician. | Drug | Target Therapy |
| CabozantinibAlso: Cabometyx, XL184Prescribed by physician. | Drug | Target Therapy |
Primary outcome
Time to decline to ≥ 2 log10 IU/mL of serum HBsAg
Time frame: Assessed up to 2 years
6 secondary outcomes
Time to loss of serum HBsAg
Time frame: Assessed up to 2 years
Time to development of anti-HBsAg
Time frame: Assessed up to 2 years
Progression-free survival (PFS) per RECIST 1.1
Time frame: From date of starting treatment until the date of objective disease progression or death, assessed up to 2 years.
Objective response rate (ORR) per RECIST 1.1
Time frame: From date of starting treatment until the date of objective disease progression or death, assessed up to 2 years.
Overall survival (OS)
Time frame: From the date of starting treatment until death due to any cause, assessed up to 2 years.
Adverse events assessed in terms of seriousness, severity, and relationship to the study material according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: From the time of signature of informed consent, throughout the treatment period, and up to the follow-up period, assessed up to 2 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2025.
- Individual participant dataSharing planned: No
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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.
George Lau, PhD principal investigator
Humanity & Health Research Centre
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, Sorafenib and Lenvatinib in people with Hepatocellular Carcinoma, run by Humanity & Health Medical Group Limited at 1 site in Hong Kong.
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 18 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 24 Mar 2025. 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 Hong Kong. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact George Lau, MD (+852-28613777, gkklau@netvigator.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to decline to ≥ 2 log10 IU/mL of serum HBsAg (time frame: Assessed up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Mar 2025.