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Carcinoma, HepatocellularNCT04180072

Atezolizumab Plus Bevacizumab With HCC and HBV Infection

A study testing Atezolizumab and Bevacizumab in people with Carcinoma, Hepatocellular, run by National Health Research Institutes, Taiwan at 7 sites in Taiwan.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is a single-arm clinical trial. The main objective is to determine the efficacy of atezolizumab+bevacizumab therapy in patients with advanced hepatocellular carcinoma and with chronic hepatitis B virus infection. All eligible patients will receive atezolizumab + bevacizumab therapy. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Carcinoma, Hepatocellular
What is being tested?
Atezolizumab and Bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
7 sitesTaiwan
Study dates
12 Mar 2020to 31 Dec 2026
Phase
Interventional
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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 20 years, according to local regulation in Taiwan, at time of signing Informed Consent Form.
  • Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology.
  • Agreement to receive a mandatory tumor biopsy for enrollment into this study.
  • Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies.
  • No prior systemic therapy (including systemic investigational agents) for HCC.
  • Documented chronic HBV infection, defined by positive serum surface antigen (HBsAg), and HBV DNA > 2000 IU/mL obtained within 28 days prior to initiation of study treatment.
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  • Agreement to receive anti-HBV treatment (per local standard of care; e.g., entecavir)
  • 1 to 2 weeks prior to study entry and willingness to continue treatment for the length of the study.
  • At least one measurable (per RECIST 1.1) lesion. Patients who received prior local therapy (e.g., radiofrequency ablation or transarterial chemoembolization, etc.) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST version 1.1.
  • ECOG Performance Status of 0 or 1 within 7 days prior to registration.
  • Child-Pugh class A (see Appendix) within 14 days prior to registration
  • Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 7 days prior to registration, unless otherwise specified:
  • ANC ≥ 1.5 x 109/L (1500/μL) without granulocyte colony-stimulating factor support; platelet count ≥ 75 x 109/L (75,000/μL) without transfusion; and hemoglobin ≥ 90 g/L (9 g/dL)(patients may be transfused to meet this criterion).
  • Liver transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN)
  • Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula)
  • Urine dipstick for proteinuria < 2+ (within 7 days prior to initiation of study treatment).
  • Patients who have ≥ 2+ proteinuria on dipstick urinalysis at baseline will be eligible if he/she have daily protein excretion of < 1 g documented by a 24-hour urine collection.
  • Women of childbearing potential must agree to use contraceptive methods with a failure rate of < 1% per year (e.g., hormonal contraceptives that inhibit ovulation, copper intrauterine devices) during the treatment period and for at least 5 months after the last dose of atezolizumab, and 6 months after the last dose of bevacizumab.
  • Men must agree to use contraceptive measures (condom plus an additional contraceptive method that together result in a failure rate of < 1% per year) during the treatment period and for 6 months after the last dose of bevacizumab.

Who cannot join

  • Histological diagnosis of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
  • Imaging finding for HCC corresponding to any of the following:
  • o Clear invasion into the bile duct
  • Co-infection of HBV and HCV. Patients with a history of HCV infection but who are negative for HCV RNA by PCR will be considered non-infected with HCV.
  • Known human immunodeficiency virus (HIV) infection.
  • History of esophageal/gastric varices or active peptic ulcers that are considered to have high risk of bleeding.
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  • History of upper gastrointestinal bleeding within 1 year.
  • Major systemic diseases that the investigator considers inappropriate for participation.
  • History of severe allergic anaphylactic reactions to antibodies or fusion proteins
  • Prior allogeneic stem cell or solid organ transplantation.
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment.
  • Prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
  • Local therapy to liver (e.g., radiofrequency ablation, transarterial chemoembolization, etc.) within 28 days prior to initiation of study treatment or non-recovery from side effects of any such procedure.
  • Radiotherapy within 28 days and abdominal/ pelvic radiotherapy within 60 days prior to initiation of study treatment, except for palliative radiotherapy to bone lesions.
  • Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
  • Presence of central nervous system (CNS) or leptomeningeal metastases. Patients with a history of CNS metastases are eligible for the study if he/she have received radiotherapy or surgery for the CNS metastases, and complete response (no evidence of residual CNS metastases) must be documented by brain CT scan at screening.
  • Any active autoimmune disease or history of known autoimmune disease except for vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • History of drug-induced pneumonitis or idiopathic pneumonitis, or Evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Known active tuberculosis or other active infection.
  • Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment. Core biopsy or other minor surgical procedure within 3 days prior to the first dose of bevacizumab
  • History of malignancy other than HCC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer.
  • Requirement of systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Inadequately controlled arterial hypertension (defined as systolic blood pressure (BP) ≥150 mmHg and/or diastolic blood pressure > 100 mmHg), based on an average of ≥ 3 BP readings on ≥ 2 sessions, despite optimal antihypertensive therapy..
  • Current or recent (within 10 days of first dose of study treatment) use of aspirin (> 325 mg/day), other anti-platelet therapy (e.g., dipyramidole, ticlopidine, clopidogrel, and cilostazol), or full dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose. However, the use of direct oral anticoagulant therapies such as dabigatran (Pradaxa) and rivaroxaban (Xarelto) is not recommended due to bleeding risk.
  • History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to initiation of study treatment
  • Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment), unstable arrhythmia, or unstable angina
  • History of uncorrectable electrolyte disorder affecting serum levels of potassium, calcium, or magnesium
  • Treatment of active infection with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
  • Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or bevacizumab formulation
  • Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding .Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Patients who have undergone an EGD within 6 months of prior to initiation of study treatment do not need to repeat the procedure.
  • A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
  • Moderate or severe ascites
  • History of hepatic encephalopathy
  • Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to initiation of study treatment
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • History of hemoptysis (≥2.5 mL of bright red blood per episode) within 1 month prior to initiation of study treatment
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • Evidence of abdominal free air that is not explained by paracentesis or recent surgical procedure
  • Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fractureMetastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses (<30 mm from the carina) of large volume Patients with vascular invasion of the portal or hepatic veins may be enrolled.
  • History of intra-abdominal inflammatory process within 6 months prior to initiation of study treatment, including but not limited to active peptic ulcer disease, diverticulitis, or colitis
  • Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., PleurX) are allowed.
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
  • Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Medical Monitor approval has been obtained. Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Taiwan7 sites

  • Chang Gung Memorial Hospital

    Linkou District

  • China Medical University Hospital

    Taichung

  • Taichung Veterans General Hospital

    Taichung

  • National Cheng Kung University Hospital

    Tainan

  • Mackay Memorial Hospital

    Taipei

  • National Taiwan University Hospital

    Taipei

  • Taipei Veterans General Hospital

    Taipei

Other trials in Taiwan

About this study

Official title: Atezolizumab Plus Bevacizumab for Patients With Advanced Hepatocellular Carcinoma (HCC) and Chronic Hepatitis B Virus (HBV) Infection

This is a single-arm clinical trial. The main objective is to determine the efficacy of atezolizumab+bevacizumab therapy in patients with advanced hepatocellular carcinoma and with chronic hepatitis B virus infection. All eligible patients will receive atezolizumab + bevacizumab therapy.

Read the detailed description

Combination of atezolizumab, an immune checkpoint inhibitors (ICI), and bevacizumab, an anti-angiogenic antibody, has shown promising anti-tumor activity and good safety profile in patients with advanced hepatocellular carcinoma (HCC) and good liver function reserves (Child-Pugh class A). Currently all trials of ICI-based therapy for HCC enrolled only patients with very low HBV viral loads if they had chronic HBV infection because of the concern of the risk of HBV reactivation on the severity and management of liver-related adverse events, particularly immune-related hepatitis.

The investigators hypothesize that in patients with advanced HCC, chronic HBV infection, and adequate liver function reserves, the safety profile of ICI-based therapy should be similar to those in other patient populations as long as prophylactic anti-HBV treatment is given, regardless the baseline HBV viral load. This is because in patients with patients with lymphoma and chronic HBV infection, who have the highest risk of HBV reactivation after cytotoxic or immunosuppressive therapy, no HBV-related complications of clinical significance were noted as long as prophylactic anti-HBV treatment started before the administration of cytotoxic or immunosuppressive therapy.

This is a single-arm clinical trial. Key eligibility criteria will include the following: histologically proven, locally advanced or metastatic and/or unresectable HCC that is not amenable to curative surgical and/or locoregional therapies; no prior systemic therapy for HCC; documented chronic HBV infection with HBV DNA > 2000 IU/mL obtained within 28 days prior to initiation of study treatment; at least one measurable (per RECIST 1.1) lesion; ECOG Performance Status of 0 or 1; and Child-Pugh class A.

All eligible patients will receive atezolizumab 1200 mg IV plus bevacizumab 15 mg/kg IV on day 1 every 3 weeks. Study treatment will continue until documented tumor progression or occurrence of unacceptable toxicity. All eligible subjects will receive anti-HBV treatment (per local standard of care; e.g., entecavir) prior to start of study treatment and continue anti-HBV treatment for the length of the study. The primary endpoint is overall response rate defined as a complete or partial response, as determined by the investigator according to RECIST v1.1. The secondary endpoints will include safety measures (e.g., the proportion of subjects with ≥ grade 3 liver-related adverse events (AE) (according to NCI CTCAE v5.0), incidence and severity of all adverse events/ immune-related adverse events, incidence of HBV reactivation/ HBV-related hepatitis flare) and efficacy measures (e.g., objective response rate, progression-free survival, duration of response, and overall survival). This study plan to enroll 48 evaluable subjects, defined as subjects who receive 3 cycles of study treatment and the first image evaluation for tumor response. The estimated time of enrollment will be 2 years.

Keywords
Carcinoma, Hepatocellular
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called Tecentriq

    Atezolizumab 1200 mg IV on day 1 every 3 weeks

  • BevacizumabDrug

    Also called Avastin

    Bevacizumab 15 mg/kg IV on day 1 every 3 weeks

Study groups in NCT04180072
Study groupRoleWhat they receive
Atezolizumab plus bevacizumabExperimentalAtezolizumab 1200 mg IV plus bevacizumab 15 mg/kg IV on day 1 every 3 weeks. Study treatment will continue until documented tumor progression or occurrence of unacceptable toxicity.
Receives: Drug: Atezolizumab; Drug: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Best overall response rate

    Complete or partial response, as determined by the investigator according to RECIST v1.1

    Measured: The last patient in has been treated for 6 months. All patients who have a PR or CR before that are responders

Secondary outcomes (10)

  1. Proportion of subjects with ≥ grade 3 liver-related adverse events (AE)

    Proportion of subjects with ≥ grade 3 liver-related adverse events (AE) according to NCI CTCAE v5.0

    Measured: 12 weeks after the first drug administration.

  2. Incidence and severity of total AE, liver related AE, and liver immune-related AE

    Any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment

    Measured: 30 days after the last dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first

  3. HBV reactivation

    (1) HBV DNA increase of ≧ 100 folds than baseline level, regardless of alanine aminotransferase (ALT) changes; (2) HBV DNA increase of ≧ 10 folds than baseline level, associated with significant ALT changes (defined as ≧ 3-fold increase in ALT, compared with baseline levels, and increase in ≧ 1 grade defined by CTCAE5.0); and (3) 2 consecutive increase in HBV DNA of ≧ 100 folds than previous nadir level, regardless of ALT changes.

    Measured: Baseline up to approximately 2.5years.

  4. HBV-related hepatitis flare

    HBV reactivation plus ≧ 3-fold increase in alanine aminotransferase (ALT), compared with baseline levels, and increase in ≧ 1 grade defined by CTCAE v 5.0

    Measured: Every 4 weeks for 6 months in permanent discontinuation of study drug treatment

  5. Progression-free survival

    The time from registration to the first occurrence of disease progression or death from any cause (whichever occurs first)

    Measured: The time from registration to the first occurrence of disease progression or death from any cause (whichever occurs first assessed up to 100 months)

  6. Time to tumor progression

    The time from registration to the first occurrence of disease progression

    Measured: The time from registration to the first occurrence of disease progression assessed up to 100 months

  7. Duration of response

    The time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first)

    Measured: The time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first assessed up to 100 months)

  8. Disease stabilization rate

    Complete response + partial response + stable disease lasting for ≧16 weeks

    Measured: Complete response + partial response + stable disease lasting for ≧16 weeks approximately1years.

  9. AFP response

    ≥ 20% decrease from baseline at the first response assessment

    Measured: 9 weeks ± 1 week after the first drug administration

  10. Overall survival

    The time from registration to death from any cause

    Measured: The time from registration to death from any cause assessed up to 100 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Nov 2019
  2. Study start12 Mar 2020
  3. Primary completion31 Dec 2025
  4. Study completion31 Dec 2026 (estimated)

Resources

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 N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04180072
Sponsor's protocol ID
T2219
Status last verified
Dec 2025
First submitted
24 Nov 2019
Last updated
9 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing Atezolizumab and Bevacizumab in people with Carcinoma, Hepatocellular, run by National Health Research Institutes, Taiwan at 7 sites 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 19 inclusion and 46 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: under way, not looking for participants, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites 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.

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?

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?

Best overall response rate (time frame: The last patient in has been treated for 6 months. All patients who have a PR or CR before that are responders). 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 NCT04180072.

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 9 Apr 2026.

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