Hepatocellular CarcinomaPhase 2PhotonABNCT06339424
Atezolizumab and Bevacizumab With Photon Radiotherapy for Unresectable Hepatocellular Carcinoma
A Phase 2 study testing Atezolizumab, Bevacizumab and Photon radiotherapy in people with Hepatocellular Carcinoma, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial summary
Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) in conjunction with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) has become the established standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). 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?
- Atezolizumab, Bevacizumab and Photon radiotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteTaiwan
- Study dates
- 30 Mar 2024to 30 Mar 2031
- 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
- Participants must have a diagnosis of HCC that is deemed unsuitable for surgical resection or transplant. Participants may have multiple lesions with a total maximal tumor dimension of < 20 cm, and no one lesion > 15 cm. Diagnosis should be confirmed by at least 1 criterion listed below:
- Histologically or cytologically proven diagnosis of HCC.
- Typical arterial enhancement and delayed washout on multiphasic CT or MRI.
- Age ≥18 years at the time of signing the informed consent document.
- ECOG performance status 0-1.
- Barcelona Clinic Liver Cancer (BCLC) stages Intermediate (B) or Advanced (C).
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- Child-Pugh score 5-6 liver function within 28 days of study registration.
- Documented virology status of hepatitis B virus (HBV), as confirmed by screening HBV serology test.
- Documented virology status of hepatitis C virus (HCV), as confirmed by screening HCV serology test.
- Ability to understand and the willingness to sign a written informed consent document
- Adequate bone marrow, liver, and renal function within 4 weeks before study registration
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count (ANC) ≥ 1,000/mm3
- Platelet count ≥ 50,000/μL
- Total bilirubin < 2.5 mg/dL
- Serum albumin >2.8 g/dL
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN)
- Prothrombin time ≤ 6 seconds prolonged
- Serum creatinine ≤ 1.5 mg/dL
Who cannot join
- Prior invasive malignancy unless disease-free for a minimum of 2 years
- Prior radiotherapy to the region of the liver that would result in overlap of radiation therapy fields
- Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
- Untreated active hepatitis B or hepatitis C
- Moderate to severe or intractable ascites
- Presence of distant metastases that cannot be encompassed by photon radiotherapy
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- Untreated or incompletely treated esophageal or gastric varices
- Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration
- Myocardial infarction within the last 6 months prior to study entry
- Acute bacterial or fungal infection requiring intravenous antibiotics within 28 days prior to study entry
- A bleeding episode within 6 months prior to study entry due to any cause.
- Thrombolytic therapy within 28 days prior to study entry.
- Known bleeding or clotting disorder.
- Uncontrolled psychotic disorder
- Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
- Prior solid organ transplantation.
- Prior or active autoimmune disease (AID) including autoimmune hepatitis, inflammatory bowel disease, myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, and multiple sclerosis.
- Prior or active thrombotic or bleeding disorders, hemoptysis, cerebral vascular accident, significant cardiac disease (ischemic or congestive heart failure), or gastrointestinal perforation.
- Inability to treat all sites of disease by photon radiotherapy (such as extrahepatic metastases or massive liver tumors whereby the liver constraints cannot be met for covering all sites of liver tumors.)
- Known HIV infection.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Taiwan1 site, 1 recruiting
- Recruiting
Chang Gung Memorial Hospital at Linkou
Taoyuan City, Taiwan, 333
Rodney Cheng-En Hsieh, MD, PhD, +88633281200 ext. 7000, rodney445@gmail.com
About this study
Official title: Investigation of Antitumor Immune Response in Patients With Unresectable Hepatocellular Carcinoma Undergoing Photon Radiotherapy Combined With Atezolizumab and Bevacizumab
Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) in conjunction with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) has become the established standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Despite an improved objective response rate (ORR) of 27%, the majority of patients face HCC progression and liver failure [Finn et al., N Engl J Med 2020]. Developing a new combined treatment strategy to overcome resistance to anti-PD-L1 and anti-VEGF is essential to improve patient outcomes.
Radiation treatment (RT) is highly efficacious in controlling localized solid tumors and has become an integral component of the treatment algorithm for unresectable HCC. Importantly, a recent retrospective cohort described that RT combined with atezolizumab plus bevacizumab was associated with favorable median overall survival of 16.1 months (Manzar et al, Cancers 2022). Our preclinical study (Hsieh et al., Science Immunology 2022) revealed that RT combined with PD-L1/PD-1 blockade induces immunogenic cell death and tumor antigen cross-presentation in antigen-presenting cells, thereby potentiating the systemic antitumor T cell responses in murine tumor models. However, whether the combinatorial therapy with RT, atezolizumab, and bevacizumab can trigger synergistic antitumor effects and systemic immune mobilization has not yet been validated in clinical trials for unresectable HCC.
Both atezolizumab/bevacizumab and X-ray RT are approved treatment methods for unresectable HCC by the U.S. and Taiwan Food and Drug Administration (FDA). The present phase II non-randomized trial aims to prospectively document the therapeutic efficacy, safety, and immunological responses in patients with unresectable HCC treated with atezolizumab/bevacizumab combined with conventional photon radiotherapy.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Atezolizumab, Bevacizumab, Photon radiotherapy
- Keywords
- Photon Radiotherapy, HCC, PD-L1, VEGF, Atezolizumab, Bevacizumab
- 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
Atezolizumab 1200 mg will be administered as an IV infusion on Day 1 of each cycle, with cycles occurring every 3 weeks. The initial dose will be delivered over 60 (± 15) minutes, and if well-tolerated, subsequent infusions may be given over 30 minutes. For patients who achieve a complete response (CR) within one year of treatment, atezolizumab should be continuously used for a year. For patients who experience a partial response (PR), atezolizumab should be continued until achieving CR or experiencing progressive disease (PD). Patients with stable disease should receive atezolizumab for 6 months. In the case of PD, atezolizumab should be discontinued at the time when PD is confirmed.
BevacizumabDrug
Bevacizumab 15 mg/kg will be administered as an IV infusion on Day 1 of each 3-week cycle. The initial dose will be delivered over 90 minutes (±15 minutes), and if well-tolerated, subsequent infusions may be given over 60 minutes. For patients who achieve a complete response (CR) within one year of treatment, bevacizumab should be continuously used for a year. In the case of patients experiencing a partial response (PR), bevacizumab should be continued until achieving CR or experiencing progressive disease (PD). Patients with stable disease should receive bevacizumab for 6 months. In the event of PD, bevacizumab should be discontinued when PD is confirmed. Temporary withholding or dose reduction of bevacizumab is permitted if patients experience adverse events such as bleeding episodes, severe hypertension, or proteinuria at the discretion of the treating physician.
Photon radiotherapyRadiation
- 39.6-72.6 Gy in 22 fractions for tumors ≤1 cm from the hepatic hilum, bowel, and heart.
- 30-66 Gy in 10 fractions for tumors >1 cm from the hepatic hilum, bowel, and heart.
- 27.5-50 Gy in 5 fractions using stereotactic body radiation therapy (SBRT) techniques
| Study group | Role | What they receive |
|---|---|---|
| Atezolizumab and bevacizumab with photon radiotherapy | Experimental | Patients undergo Atezolizumab and Bevacizumab with photon radiotherapy. Receives: Drug: Atezolizumab; Drug: Bevacizumab; Radiation: Photon radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS)
PFS is defined as the time from signing the informed consent to the first occurrence of disease progression or death from any cause (whichever occurs first) according to RECIST1.1.
Measured: 12 months
Secondary outcomes (5)
Local control (LC)
LC is defined as the time from signing the informed consent to the first occurrence of disease progression in the irradiated field according to RECIST1.1.
Measured: 12 months
Time to progression (TTP)
TTP is defined as the time from signing the informed consent to the first occurrence of disease progression according to RECIST1.1.
Measured: 12 months
Overall Response Rate (ORR)
ORR is defined as a complete or partial response according to RECIST1.1.
Measured: 12 months
Overall survival (OS)
OS is defined as the time from signing the informed consent to death from any cause.
Measured: 12 months
Incidence and severity of adverse events
Adverse events will be graded using CTCAE v5
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2024
- Study start30 Mar 2024
- Primary completion30 Mar 2029 (estimated)
- Study completion30 Mar 2031 (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.
- More trials run by Chang Gung Memorial 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
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06339424
- Sponsor's protocol ID
- 202400156A3
- Acronym
- PhotonAB
- Status last verified
- Sep 2026
- First submitted
- 25 Mar 2024
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Sharing individual participant data (IPD) with other researchers requires IRB review and approval. Presently, we do not have a plan to provide IPD to other researchers
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Antitumor Immune Response in Patients With Unresectable Hepatocellular Carcinoma Undergoing Photon Radiotherapy Combined With Atezolizumab and Bevacizumab
- ClinicalTrials.gov ID
- NCT06339424
- Acronym / sponsor ID
- PhotonAB / 202400156A3
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Photon Radiotherapy, HCC, PD-L1, VEGF, Atezolizumab, Bevacizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- 30 Mar 2024 (actual)
- Primary completion
- 30 Mar 2029 (estimated)
- Study completion
- 30 Mar 2031 (estimated)
- First posted
- 1 Apr 2024 (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.
Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) in conjunction with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) has become the established standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Despite an improved objective response rate (ORR) of 27%, the majority of patients face HCC progression and liver failure [Finn et al., N Engl J Med 2020]. Developing a new combined treatment strategy to overcome resistance to anti-PD-L1 and anti-VEGF is essential to improve patient outcomes.
Radiation treatment (RT) is highly efficacious in controlling localized solid tumors and has become an integral component of the treatment algorithm for unresectable HCC. Importantly, a recent retrospective cohort described that RT combined with atezolizumab plus bevacizumab was associated with favorable median overall survival of 16.1 months (Manzar et al, Cancers 2022). Our preclinical study (Hsieh et al., Science Immunology 2022) revealed that RT combined with PD-L1/PD-1 blockade induces immunogenic cell death and tumor antigen cross-presentation in antigen-presenting cells, thereby potentiating the systemic antitumor T cell responses in murine tumor models. However, whether the combinatorial therapy with RT, atezolizumab, and bevacizumab can trigger synergistic antitumor effects and systemic immune mobilization has not yet been validated in clinical trials for unresectable HCC.
Both atezolizumab/bevacizumab and X-ray RT are approved treatment methods for unresectable HCC by the U.S. and Taiwan Food and Drug Administration (FDA). The present phase II non-randomized trial aims to prospectively document the therapeutic efficacy, safety, and immunological responses in patients with unresectable HCC treated with atezolizumab/bevacizumab combined with conventional photon radiotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Atezolizumab and bevacizumab with photon radiotherapy | Experimental | Drug: Atezolizumab, Drug: Bevacizumab, Radiation: Photon radiotherapyPatients undergo Atezolizumab and Bevacizumab with photon radiotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Participants must have a diagnosis of HCC that is deemed unsuitable for surgical resection or transplant. Participants may have multiple lesions with a total maximal tumor dimension of < 20 cm, and no one lesion > 15 cm. Diagnosis should be confirmed by at least 1 criterion listed below:
- Age ≥18 years at the time of signing the informed consent document.
- ECOG performance status 0-1.
- Barcelona Clinic Liver Cancer (BCLC) stages Intermediate (B) or Advanced (C).
- Child-Pugh score 5-6 liver function within 28 days of study registration.
Key exclusion criteria (21 listed)
- Prior invasive malignancy unless disease-free for a minimum of 2 years
- Prior radiotherapy to the region of the liver that would result in overlap of radiation therapy fields
- Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
- Untreated active hepatitis B or hepatitis C
- Moderate to severe or intractable ascites
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 |
|---|---|---|
| AtezolizumabAtezolizumab 1200 mg will be administered as an IV infusion on Day 1 of each cycle, with cycles occurring every 3 weeks. The initial dose will be delivered over 60 (± 15) minutes, and if well-tolerated, subsequent infusions may be given over 30 minutes. For patients who achieve a complete response (CR) within one year of treatment, atezolizumab should be continuously used for a year. For patients who experience a partial response (PR), atezolizumab should be continued until achieving CR or experiencing progressive disease (PD). Patients with stable disease should receive atezolizumab for 6 months. In the case of PD, atezolizumab should be discontinued at the time when PD is confirmed. | Drug | Atezolizumab and bevacizumab with photon radiotherapy |
| BevacizumabBevacizumab 15 mg/kg will be administered as an IV infusion on Day 1 of each 3-week cycle. The initial dose will be delivered over 90 minutes (±15 minutes), and if well-tolerated, subsequent infusions may be given over 60 minutes. For patients who achieve a complete response (CR) within one year of treatment, bevacizumab should be continuously used for a year. In the case of patients experiencing a partial response (PR), bevacizumab should be continued until achieving CR or experiencing progressive disease (PD). Patients with stable disease should receive bevacizumab for 6 months. In the event of PD, bevacizumab should be discontinued when PD is confirmed. Temporary withholding or dose reduction of bevacizumab is permitted if patients experience adverse events such as bleeding episodes, severe hypertension, or proteinuria at the discretion of the treating physician. | Drug | Atezolizumab and bevacizumab with photon radiotherapy |
| Photon radiotherapy* 39.6-72.6 Gy in 22 fractions for tumors ≤1 cm from the hepatic hilum, bowel, and heart. * 30-66 Gy in 10 fractions for tumors >1 cm from the hepatic hilum, bowel, and heart. * 27.5-50 Gy in 5 fractions using stereotactic body radiation therapy (SBRT) techniques | Radiation | Atezolizumab and bevacizumab with photon radiotherapy |
Primary outcome
Progression free survival (PFS)
Time frame: 12 months
PFS is defined as the time from signing the informed consent to the first occurrence of disease progression or death from any cause (whichever occurs first) according to RECIST1.1.
5 secondary outcomes
Local control (LC)
Time frame: 12 months
Time to progression (TTP)
Time frame: 12 months
Overall Response Rate (ORR)
Time frame: 12 months
Overall survival (OS)
Time frame: 12 months
Incidence and severity of adverse events
Time frame: 12 months
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 1 Oct 2026.
- Individual participant dataSharing planned: No. Sharing individual participant data (IPD) with other researchers requires IRB review and approval. Presently, we do not have a plan to provide IPD to other researchers
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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.
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 Atezolizumab, Bevacizumab and Photon radiotherapy in people with Hepatocellular Carcinoma, run by Chang Gung Memorial 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 19 inclusion and 21 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 1 Oct 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?
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 Rodney Cheng-En Hsieh, MD, PhD (+886-3-3281200 ext. 7000, rodney445@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) (time frame: 12 months). 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 1 Oct 2026.