Atezolizumab Plus Bevacizumab Alone or Combined With External Beam Radiotherapy for HCC With Macrovascular Invasion (ALERT-HCC)
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.
Обзор исследования
Статус
Условия
Подробное описание
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).
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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.
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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).
Тип исследования
Регистрация (Действительный)
Фаза
- Фаза 2
Контакты и местонахождение
Места учебы
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-
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Seoul, Южная Корея
- Asan Medical Center
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Inclusion Criteria:
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Older than 19 years of age, lower than 80 years of age
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Child-Pugh class A hepatic function
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Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
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Patients with HCC [diagnosed according to AASLD guidelines] invading the intrahepatic vascular system
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No prior systemic therapy for HCC
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At least one measurable HCC lesion with ≥ 1cm diameter
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Adequate hematologic and organ function
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count ≥ 1,000 /mm3
- Platelet ≥ 50,000/ mm3 without transfusion
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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
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
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Экспериментальный: Radiotherapy combination
Atezolizumab+Bevacizumab, combined EBRT to vascular invasion
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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. |
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Активный компаратор: Atezolizumab+Bevacizumab
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Atezolizumab plus bevacizumab q3w |
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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progression-free survival rate
Временное ограничение: up to approximately 3 years
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Randomization to the first occurrence of disease progression or death from any cause, whichever occurs first |
up to approximately 3 years
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Overall survival rate
Временное ограничение: up to approximately 3 years
|
Randomization to death from any cause, through the end of study |
up to approximately 3 years
|
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Objective response
Временное ограничение: 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
|
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Adverse reaction rate
Временное ограничение: through study completion, up to approximately 3 years
|
Adverse reaction rate assessed by CTCAE version 5 |
through study completion, up to approximately 3 years
|
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Time to deterioration
Временное ограничение: through study completion, up to approximately 3 years
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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
|
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Duration of response
Временное ограничение: up to approximately 3 years
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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
|
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Tumor marker response (AFP, PIVKA-II)
Временное ограничение: through study completion, up to approximately 3 years
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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
|
Соавторы и исследователи
Спонсор
Соавторы
Следователи
- Главный следователь: Ju Hyun Shim, Asan Medical Center
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Действительный)
Завершение исследования (Действительный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Дополнительные соответствующие термины MeSH
- Новообразования по локализации
- Новообразования
- Новообразования по гистологическому типу
- Новообразования пищеварительной системы
- Заболевания пищеварительной системы
- Заболевания печени
- Новообразования железистые и эпителиальные
- Аденокарцинома
- Карцинома
- Карцинома, гепатоцеллюлярная
- Новообразования печени
- Аминокислоты, пептиды и белки
- Белки
- Антитела, моноклональные, гуманизированные
- Антитела, моноклональные
- Антитела
- Иммуноглобулины
- Иммунопротеины
- Белки крови
- Сывороточные глобулины
- Глобулины
- Бевацизумаб
- Атезолизумаб
Другие идентификационные номера исследования
- KCT0007365
- KCT0007365 (Идентификатор реестра: CRIS (International Clinical Trials Registry Platform))
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
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