Unresectable Hepatocellular CarcinomaNCT07824765
Heterogeneity of Treatment Effects of Adding Locoregional Therapies to Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma (ISMIO-026)
An observational study of Unresectable Hepatocellular Carcinoma, run by Zhongda Hospital at 1 site in China.
Trial summary
uHCC imposes a substantial disease burden in China and the Asia-Pacific region. Atezo+Bev is an important first-line regimen for patients who have not received prior systemic therapy; however, not all patients achieve adequate and durable tumor control. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unresectable Hepatocellular Carcinoma
- How many people
- 2,658 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2026to 31 Dec 2027
- How long will I take part?
- 36 Months
- Phase
- Observational
- 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
Study population: Adults with uHCC who initiate first-line Atezo+Bev and have received no prior systemic therapy for HCC.
Who may be able to join
- Age ≥18 years on the index date.
- Receipt of at least one dose each of atezolizumab and bevacizumab as part of the same first-line combination regimen, with an interval of ≤28 days between the first administrations of the two drugs.
- At least one intrahepatic lesion amenable to a protocol-specified LRT on the index date, with no absolute contraindication to Atezo+Bev or to all feasible LRTs.
- A clinical, radiologic, or pathologic diagnosis of uHCC on or before the index date; baseline EHS is permitted.
- Survival status or the date last known alive after the index date can be ascertained.
- No systemic therapy for HCC before the regimen initiation date.
Show all 9Show fewer
- No LRT within 60 days before the index date or between baseline imaging and the index date; earlier prior LRTs are permitted provided that an untreated, measurable intrahepatic lesion remains.
- A technically adequate baseline contrast-enhanced CT/MRI examination and at least one untreated intrahepatic lesion that can be delineated and evaluated.
- Baseline ECOG performance status of 0-2.
Who cannot join
- Another primary malignancy requiring active systemic treatment on the index date, except for a malignancy that has been cured and has a low risk of recurrence.
- Participation on the index date in an interventional study that could affect treatment allocation or outcome assessment.
- Suitability for immediate curative resection or liver transplantation following multidisciplinary assessment.
- An absolute contraindication to Atezo+Bev or to all feasible LRTs.
- Active autoimmune disease or immunodeficiency requiring systemic immunosuppression or constituting a contraindication to atezolizumab.
- Inadequately controlled high-risk esophageal/gastric varices, recent variceal bleeding, an uncorrected bleeding tendency, or clinically significant coagulopathy.
- Inability to determine the index date, primary treatment strategy, OS outcome/censoring date, or absence of a technically adequate baseline contrast-enhanced CT/MRI examination.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Zhongda hospital
Nanjing, Jiangsu, 213003
Jun-Hao Mei, 15052007938, jh_mei240225@126.com
About this study
Official title: Heterogeneity of Treatment Effects of Adding Locoregional Therapies to Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma Based on Clinical and Multiregional, Multiphase Contrast-Enhanced CT/MRI Features (ISMIO-026)
uHCC imposes a substantial disease burden in China and the Asia-Pacific region. Atezo+Bev is an important first-line regimen for patients who have not received prior systemic therapy; however, not all patients achieve adequate and durable tumor control. In clinical practice, ablation, radiotherapy, or transarterial therapy is often added to Atezo+Bev to intensify intrahepatic disease control. The indications, timing, efficacy, and risk of liver-function impairment vary across LRTs. Most existing studies report average treatment effects and often use TACE as a fixed backbone, and therefore do not directly identify which patients receiving Atezo+Bev should receive early LRTs.
Using target trial emulation and HTE analysis, this study will integrate baseline clinical variables with pretreatment contrast-enhanced CT/MRI features to estimate the CATE of early LRT initiation and identify patients likely to achieve greater survival benefit.
- Conditions
- Unresectable Hepatocellular Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Training Cohort | Not described | |
| Retrospective validation cohort | Not described | |
| Prospective validation cohort | Not described | |
| Biological validation cohort | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
With OS as the primary outcome, to estimate the overall treatment effect and CATE of initiating LRTs within 60 days after Atezo+Bev initiation versus not initiating LRTs within 60 days; and to integrate baseline clinical variables with multiregional radiomic, dynamic/habitat, and deep representation features from pretreatment contrast-enhanced CT/MRI to develop and validate an HTE decision model.
Measured: through study completion, an average of 1 year
Secondary outcomes (3)
Model calibration
Measured: through study completion, an average of 1 year
Benefit ranking
Measured: through study completion, an average of 1 year
PFS/mPFS
Defined as the time from index date to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1 or mRECIST.
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2026
- Study start1 Sep 2026 (estimated)
- Primary completion1 Sep 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,658 participants (estimated)
- Target duration
- 36 Months
Sponsor and investigators
- Lead sponsor
- Zhongda Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jian Lu, Zhongda Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07824765
- Sponsor's protocol ID
- ISMIO-026
- Status last verified
- Sep 2026
- First submitted
- 1 Sep 2026
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Heterogeneity of Treatment Effects of Adding Locoregional Therapies to Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma Based on Clinical and Multiregional, Multiphase Contrast-Enhanced CT/MRI Features (ISMIO-026)
- ClinicalTrials.gov ID
- NCT07824765
- Acronym / sponsor ID
- ISMIO-026
- Conditions
- Unresectable Hepatocellular Carcinoma
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 2,658 participants (estimated)
- Lead sponsor
- Zhongda HospitalUniversity, hospital or other
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 1 Sep 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 17 Sep 2026 (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.
uHCC imposes a substantial disease burden in China and the Asia-Pacific region. Atezo+Bev is an important first-line regimen for patients who have not received prior systemic therapy; however, not all patients achieve adequate and durable tumor control. In clinical practice, ablation, radiotherapy, or transarterial therapy is often added to Atezo+Bev to intensify intrahepatic disease control. The indications, timing, efficacy, and risk of liver-function impairment vary across LRTs. Most existing studies report average treatment effects and often use TACE as a fixed backbone, and therefore do not directly identify which patients receiving Atezo+Bev should receive early LRTs.
Using target trial emulation and HTE analysis, this study will integrate baseline clinical variables with pretreatment contrast-enhanced CT/MRI features to estimate the CATE of early LRT initiation and identify patients likely to achieve greater survival benefit.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 36 Months
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Training Cohort | – | – |
| Retrospective validation cohort | – | – |
| Prospective validation cohort | – | – |
| Biological validation cohort | – | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults with uHCC who initiate first-line Atezo+Bev and have received no prior systemic therapy for HCC.
Key inclusion criteria (9 listed)
- Age ≥18 years on the index date.
- Receipt of at least one dose each of atezolizumab and bevacizumab as part of the same first-line combination regimen, with an interval of ≤28 days between the first administrations of the two drugs.
- At least one intrahepatic lesion amenable to a protocol-specified LRT on the index date, with no absolute contraindication to Atezo+Bev or to all feasible LRTs.
- A clinical, radiologic, or pathologic diagnosis of uHCC on or before the index date; baseline EHS is permitted.
- Survival status or the date last known alive after the index date can be ascertained.
Key exclusion criteria (7 listed)
- Another primary malignancy requiring active systemic treatment on the index date, except for a malignancy that has been cured and has a low risk of recurrence.
- Participation on the index date in an interventional study that could affect treatment allocation or outcome assessment.
- Suitability for immediate curative resection or liver transplantation following multidisciplinary assessment.
- An absolute contraindication to Atezo+Bev or to all feasible LRTs.
- Active autoimmune disease or immunodeficiency requiring systemic immunosuppression or constituting a contraindication to atezolizumab.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Overall survival
Time frame: through study completion, an average of 1 year
With OS as the primary outcome, to estimate the overall treatment effect and CATE of initiating LRTs within 60 days after Atezo+Bev initiation versus not initiating LRTs within 60 days; and to integrate baseline clinical variables with multiregional radiomic, dynamic/habitat, and deep representation features from pretreatment contrast-enhanced CT/MRI to develop and validate an HTE decision model.
3 secondary outcomes
Model calibration
Time frame: through study completion, an average of 1 year
Benefit ranking
Time frame: through study completion, an average of 1 year
PFS/mPFS
Time frame: through study completion, an average of 1 year
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 17 Sep 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Unresectable Hepatocellular Carcinoma
Not yet recruitingPhase 2
PEARL Trial: Partial TACE Enhancing Anti-tumor Response With Lenvatinib in Unresectable HCC
Hepatocellular Carcinoma
Active, not recruitingPhase 3
Radiation Therapy With Protons or Photons in Treating Patients With Liver Cancer
Recurrent Hepatocellular Carcinoma, Stage III Hepatocellular Carcinoma AJCC v7
Active, not recruitingPhase 1/2
Nivolumab, Fluorouracil, and Interferon Alpha 2B for the Treatment of Unresectable Fibrolamellar Cancer
Stage III Hepatocellular Carcinoma AJCC v8, Stage IIIA Hepatocellular Carcinoma AJCC v8
Not yet recruitingObservational study
Immune-Related Adverse Events and Clinical Outcomes of First-Line Immunotherapy in Egyptian Patients With Unresectable Hepatocellular Carcinoma
Hepatocellular Carcinoma, Hepatocellular Carcinoma (HCC)
Active, not recruiting
BioPearl™ Microspheres Loaded With Doxorubicin for the Treatment of Unresectable Hepatocellular Carcinoma (HCC)
Hepatocellular Carcinoma Non-resectable
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?
An observational study of Unresectable Hepatocellular Carcinoma, run by Zhongda Hospital at 1 site in China.
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 9 inclusion and 7 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: opening soon, as of the sponsor's last update on 17 Sep 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 China. 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?
Contact Jian Lu (13616106021, lujian43307131@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: through study completion, an average of 1 year). 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 17 Sep 2026.