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Hepatocellular CarcinomaPhase 2ALERT-HCCNCT05992220

Atezolizumab Plus Bevacizumab Alone or Combined with External Beam Radiotherapy for HCC with Macrovascular Invasion

A Phase 2 study testing Atezolizumab plus bevacizumab, combined EBRT to vascular invasion and Atezolizumab plus bevacizumab in people with Hepatocellular Carcinoma and Hepatocellular Cancer, run by Asan Medical Center at 1 site in South Korea.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The recent global IMbrave150 study evaluated the combination of atezolizumab and bevacizumab versus sorafenib in 501 patients with advanced or metastatic Hepatocellular Carcinoma (HCC). The median overall survival (OS) was notably better in the atezolizumab/bevacizumab group. Read more about this study

Who is it for?
Ages 20 to 79 years
What is being tested?
Atezolizumab plus bevacizumab, combined EBRT to vascular invasion and Atezolizumab plus bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
138 participants
Where
1 siteSouth Korea
Study dates
22 Oct 2022to Mar 2026
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 20 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Older than 19 years of age, lower than 80 years of age
  • Child-Pugh class A hepatic function
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
  • Patients with HCC [diagnosed according to AASLD guidelines] invading the intrahepatic vascular system
  • No prior systemic therapy for HCC
  • At least one measurable HCC lesion with ≥ 1cm diameter
Show all 11Show fewer
  • Adequate hematologic and organ function
  • Hemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count ≥ 1,000 /mm3
  • Platelet ≥ 50,000/ mm3 without transfusion
  • Total bilirubin ≤ 2.5 mg/dL

Who cannot join

  • Treatment history of prior systemic treatment of HCC
  • Liver transplant recipients
  • Patients with peptic ulcer, untreated or incompletely treated varices with bleeding or high-risk for bleeding
  • Any serious illness (e.g., active infection or inflammatory condition) or uncontrolled severe medical comorbidity
  • A history of treated malignancy (other than HCC) is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding two years
  • Abdominal/pelvic radiotherapy within 28 days prior to initiation of study treatment, except palliative radiotherapy to bone lesions within 7 days prior to initiation of study treatment

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jihyun An contact

82-31-560-2209

starlit1@naver.com

Ju Hyun Shim contact

s5854@amc.seoul.kr

South Korea1 site, 1 recruiting

  • Asan Medical Center

    Seoul

    Ju Hyun Shim

    Recruiting

Other trials in South Korea

About this study

Official title: A Randomized, Multicenter, Open-Label, Phase II Trial of Atezolizumab Plus Bevacizumab Alone or Combined with External Beam RadioTherapy for HepatoCellular Carcinoma with Macrovascular Invasion (ALERT-HCC)

The recent global IMbrave150 study evaluated the combination of atezolizumab and bevacizumab versus sorafenib in 501 patients with advanced or metastatic Hepatocellular Carcinoma (HCC). The median overall survival (OS) was notably better in the atezolizumab/bevacizumab group. However, for HCC patients with intrahepatic macrovascular invasion (MVI), the prognosis remains poor, indicating a significant unmet need in this group.

External Beam Radiotherapy (EBRT) has shown promising results in treating HCC with MVI, especially when used in combination with trans-arterial chemoembolization (TACE). It has been reported that radiotherapy may make tumor cells more susceptible to immune-mediated therapy, potentially enhancing the effects of atezolizumab and bevacizumab.

Thus, this study aims to investigate the efficacy and safety of atezolizumab/bevacizumab alone versus atezolizumab/bevacizumab in combination with EBRT in HCC patients with macrovascular invasion.

Read the detailed description

A total of 138 subjects are randomly assigned to one of two treatment groups (69 patients in the atezolizumab+bevacizumab group and 69 patients in the Atezolizumab plus Bevacizumab combined EBRT group).

  • Radiotherapy combination:
  • Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21day cycle.
  • Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21day cycle.
  • The external beam radiotherapy will commence after day 2 of the first cycle of Atezolizumab+Bevacizumab, and will be delivered in accordance with institutional protocol.
  • Atezolizumab+Bevacizumab:
  • Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21day cycle.
  • Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21day cycle.

Additional study identifiers: This study was also registered on the WHO's International Clinical Trials Registry Platform, CRIS, before the first participant was enrolled (ID: KCT0007365, Date of registration: 2022-06-08).

Being tested
Atezolizumab plus bevacizumab, combined EBRT to vascular invasion, Atezolizumab plus bevacizumab
Keywords
HCC; vascular invasion; portal vein tumor thrombosis; BCLC stage C
Medical subject headings
Carcinoma, Hepatocellular, Liver Neoplasms

What participants receive

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

  • Atezolizumab plus bevacizumab, combined EBRT to vascular invasionRadiation

    The external beam radiotherapy will commence after day 2 of the first cycle of atezolizumab+bevacizumab, and will be delivered in accordance with institutional protocol.

    3D-conformal radiotherapy technique is used to determine target volumes, radiation ports, and dose prescriptions by using a 3D radiotherapy planning system.

    The gross tumor volume (GTV) includes vascular invasion and a 2-cm margin into the contiguous HCC. The GTV can consist of the entire HCC and vascular invasion at the discretion of the investigator.

    The target dose is 45 Gy, however, the total dose can be reduced as low as 30 Gy according to the liver function, liver volumes, or the maximum dose to the stomach/duodenum during the planning process according to the judgment of the radiation oncologist of each participating sites.

  • Atezolizumab plus bevacizumabDrug

    Atezolizumab plus bevacizumab q3w

Study groups in NCT05992220
Study groupRoleWhat they receive
Radiotherapy combinationExperimentalAtezolizumab+Bevacizumab, combined EBRT to vascular invasion * Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21day cycle. * Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21day cycle. * The external beam radiotherapy will commence after day 2 of the first cycle of A+B, and will be delivered in accordance with institutional protocol.
Receives: Radiation: Atezolizumab plus bevacizumab, combined EBRT to vascular invasion
Atezolizumab+BevacizumabActive comparator* Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21day cycle. * Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21day cycle.
Receives: Drug: Atezolizumab plus bevacizumab

What is being measured

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

  1. progression-free survival rate

    Randomization to the first occurrence of disease progression or death from any cause, whichever occurs first

    Measured: up to approximately 3 years

Secondary outcomes (6)

  1. Overall survival rate

    Randomization to death from any cause, through the end of study

    Measured: up to approximately 3 years

  2. Objective response

    complete response or partial response as determined by the Investigator according to RECIST V1.1

    Measured: up to approximately 3 years

  3. Adverse reaction rate

    Adverse reaction rate assessed by CTCAE version 5

    Measured: through study completion, up to approximately 3 years

  4. Time to deterioration

    The time from randomization to first deterioration (decrease from baseline of ≥10 points) in the patient-reported global health status (GHS) / Quality of life (QoL), physical function, or role function scales of the EORTC QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks

    Measured: through study completion, up to approximately 3 years

  5. Duration of response

    the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression or death is documented, whichever occurs first. DOR will be assessed in patients who had an objective response.

    Measured: up to approximately 3 years

  6. Tumor marker response (AFP, PIVKA-II)

    The decrease of >20% in serum concentration of each marker from baseline across all time points during study period.

    Measured: through study completion, up to approximately 3 years

Timeline

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

  1. First posted15 Aug 2023
  2. Study start22 Oct 2022
  3. Primary completionMar 2026 (estimated)
  4. Study completionMar 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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
randomized, multicenter, open-label study
Masking
None (open label)
Enrolment
138 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05992220
Sponsor's protocol ID
KCT0007365
Other IDs
KCT0007365
Acronym
ALERT-HCC
Status last verified
Jan 2025
First submitted
27 Jul 2023
Last updated
21 Feb 2025
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 Phase 2 study testing Atezolizumab plus bevacizumab, combined EBRT to vascular invasion and Atezolizumab plus bevacizumab in people with Hepatocellular Carcinoma and Hepatocellular Cancer, run by Asan Medical Center at 1 site in South Korea.

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 11 inclusion and 6 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 21 Feb 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 South Korea. 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 Jihyun An (82-31-560-2209, starlit1@naver.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

progression-free survival rate (time frame: up to approximately 3 years). 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 NCT05992220.

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 21 Feb 2025.

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