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

5 novembre 2026 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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).

Type d'étude

Interventionnel

Inscription (Réel)

138

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

20 ans à 79 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Radiation: 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.
Comparateur actif: 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.
Médicament: Atezolizumab plus bevacizumab

Atezolizumab plus bevacizumab q3w

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
progression-free survival rate
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Overall survival rate
Délai: up to approximately 3 years

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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Asan Medical Center

Collaborateurs

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

Les enquêteurs

  • Chercheur principal: Ju Hyun Shim, Asan Medical Center

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

22 octobre 2022

Achèvement primaire (Réel)

25 février 2026

Achèvement de l'étude (Réel)

25 février 2026

Dates d'inscription aux études

Première soumission

27 juillet 2023

Première soumission répondant aux critères de contrôle qualité

7 août 2023

Première publication (Réel)

15 août 2023

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

9 novembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

5 novembre 2026

Dernière vérification

1 juillet 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • KCT0007365
  • KCT0007365 (Identificateur de registre: CRIS (International Clinical Trials Registry Platform))

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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