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)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- progression-free survival rate
研究概览
简要总结
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.
详细描述
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:
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Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21day cycle.
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Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21day cycle.
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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.
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Atezolizumab+Bevacizumab:
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Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21day cycle.
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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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Atezolizumab plus bevacizumab, combined EBRT to vascular invasion (Radiation)
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.
干预措施: Atezolizumab plus bevacizumab (Drug)
结局指标
主要结局
progression-free survival rate
时间窗: up to approximately 3 years
Randomization to the first occurrence of disease progression or death from any cause, whichever occurs first
次要结局
- Time to deterioration(through study completion, up to approximately 3 years)
- Objective response(up to approximately 3 years)
- Adverse reaction rate(through study completion, up to approximately 3 years)
- Tumor marker response (AFP, PIVKA-II)(through study completion, up to approximately 3 years)
- Overall survival rate(up to approximately 3 years)
- Duration of response(up to approximately 3 years)
研究者
Ju Hyun Shim
Principal Investigator
Asan Medical Center