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Atezolizumab Plus Bevacizumab Alone or Combined With External Beam Radiotherapy for HCC With Macrovascular Invasion (ALERT-HCC)

5 november 2026 uppdaterad av: Ju Hyun Shim, Asan Medical Center

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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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).

Studietyp

Interventionell

Inskrivning (Faktisk)

138

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Sydkorea
      • Seoul, Sydkorea
        • Asan Medical Center

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

20 år till 79 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  • 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

  • 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

Exclusion Criteria:

  • 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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Radiotherapy combination

Atezolizumab+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.
Strålning: Atezolizumab plus bevacizumab, combined EBRT to vascular invasion

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.
Aktiv komparator: 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.
Läkemedel: Atezolizumab plus bevacizumab

Atezolizumab plus bevacizumab q3w

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
progression-free survival rate
Tidsram: up to approximately 3 years

Randomization to the first occurrence of disease progression or death from any cause, whichever occurs first
up to approximately 3 years

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Overall survival rate
Tidsram: up to approximately 3 years

Randomization to death from any cause, through the end of study
up to approximately 3 years
Objective response
Tidsram: up to approximately 3 years

complete response or partial response as determined by the Investigator according to RECIST V1.1
up to approximately 3 years
Adverse reaction rate
Tidsram: through study completion, up to approximately 3 years

Adverse reaction rate assessed by CTCAE version 5
through study completion, up to approximately 3 years
Time to deterioration
Tidsram: through study completion, up to approximately 3 years

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
through study completion, up to approximately 3 years
Duration of response
Tidsram: up to approximately 3 years

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.
up to approximately 3 years
Tumor marker response (AFP, PIVKA-II)
Tidsram: through study completion, up to approximately 3 years

The decrease of >20% in serum concentration of each marker from baseline across all time points during study period.
through study completion, up to approximately 3 years

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Asan Medical Center

Samarbetspartners

Seoul National University Hospital
Soon Chun Hyang University
Hanyang University Guri Hospital

Utredare

  • Huvudutredare: Ju Hyun Shim, Asan Medical Center

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

22 oktober 2022

Primärt slutförande (Faktisk)

25 februari 2026

Avslutad studie (Faktisk)

25 februari 2026

Studieregistreringsdatum

Först inskickad

27 juli 2023

Först inskickad som uppfyllde QC-kriterierna

7 augusti 2023

Första postat (Faktisk)

15 augusti 2023

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

9 november 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

5 november 2026

Senast verifierad

1 juli 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • KCT0007365
  • KCT0007365 (Registeridentifierare: CRIS (International Clinical Trials Registry Platform))

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Nej

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

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