NCT04102098已完成3 期
A Phase III, Multicenter, Randomized, Open-Label Study of Atezolizumab (Anti-PD-L1 Antibody) Plus Bevacizumab Versus Active Surveillance as Adjuvant Therapy in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Surgical Resection or Ablation
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 668
- 试验地点
- 255
- 主要终点
- Recurrence-Free Survival (RFS), as Determined by IRF
研究概览
简要总结
This study will evaluate the efficacy and safety of adjuvant therapy with atezolizumab plus bevacizumab compared with active surveillance in participants with completely resected or ablated hepatocellular carcinoma (HCC) who are at high risk for disease recurrence.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with a first diagnosis of HCC who have undergone either a curative resection or ablation (radiofrequency ablation [RFA] or microwave ablation [MVA] only) within 4-12 weeks prior to randomization
- •Documented diagnosis of HCC that has been completely resected or ablated (RFA or MVA only)
- •Absence of major macrovascular invasion (except Vp1/Vp2) and extrahepatic spread
- •Absence of extrahepatic spread as confirmed by CT or MRI scan of the chest, abdomen, pelvis, and head prior to and following curative procedure
- •Full recovery from surgical resection or ablation within 4 weeks prior to randomization
- •High risk for HCC recurrence after resection or ablation
- •For patients who received post-operative transarterial chemoembolization: full recovery from the procedure within 4 weeks prior to randomization
- •For patients with resected HCC, availability of a representative baseline tumor tissue sample
- •ECOG Performance Status of 0 or 1
- •Child-Pugh Class A status
- •Adequate hematologic and end-organ function
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods
- •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm
排除标准
- •Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- •Evidence of residual, recurrent, or metastatic disease at randomization
- •Clinically significant ascites
- •History of hepatic encephalopathy
- •Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization
- •Have received more than 1 cycle of adjuvant TACE following surgical resection
- •Active or history of autoimmune disease or immune deficiency
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
- •Significant cardiovascular disease within 3 months prior to Day 1 of Cycle 1, unstable arrhythmia, or unstable angina
- •History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
- •Active tuberculosis
- •Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
- •Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of atezolizumab or within 6 months after the final dose of bevacizumab. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to Day 1 of Cycle
- •Co-infection with HBV and HCV
- •Co-infection with HBV and hepatitis D viral infection
- •Clinical significant uncontrolled or symptomatic hypercalcemia
- •Any treatment for HCC prior to resection or ablation, including systemic therapy and locoregional therapy such as TACE
- •Treatment with systemic immunostimulatory or immunosuppressive agents
- •Inadequately controlled arterial hypertension
- •History of hypertensive crisis or hypertensive encephalopathy
- •Significant vascular disease
- •Evidence of bleeding diathesis or significant coagulopathy
- •Current or recent use of aspirin or full-dose oral or parenteral anticoagulants
- •Core biopsy within 3 days of Day 1 of Cycle 1
- •History of GI fistula, GI perforation, or intra-abdominal abscess
- •Serious non-healing or dehiscing wound
- •Major surgical procedure within four weeks
- •Chronic daily treatment with a non-steroidal anti-inflammatory drug
研究组 & 干预措施
Arm A (atezolizumab plus bevacizumab)
Experimental
Participants will receive Atezolizumab + Bevacizumab until disease recurrence or unacceptable toxicity.
干预措施: Bevacizumab (Drug)
Arm A (atezolizumab plus bevacizumab)
Experimental
Participants will receive Atezolizumab + Bevacizumab until disease recurrence or unacceptable toxicity.
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Recurrence-Free Survival (RFS), as Determined by IRF
时间窗: Baseline up to approximately 33 months
RFS is defined as the time from randomization to the first documented occurrence of intrahepatic or extrahepatic HCC as determined by an IRF, or death from any cause (whichever occurs first).
次要结局
- RFS as Determined by the Investigator(Baseline up to approximately 91 months)
- RFS Rate at 24 and 36 Months, as Assessed by the IRF(Randomization up to 24 months and up to 36 months)
- OS Rate at 24 and 36 Months(Baseline to 24 and 36 months)
- Overall Survival (OS)(Baseline up to approximately 91 months)
- RFS Rate at 24 and 36 Months, as Assessed by the Investigator(Randomization up to 24 months and up to 36 months)
- RFS in Pd-L1-High Subgroup(Baseline up to approximately 91 months)
- Percentage of Participants With Adverse Events(Baseline up to approximately 91 months)
- Time to Recurrence (TTR)(Baseline up to approximately 91 months)
- Time to Extrahepatic Spread (EHS) or Macrovascular Invasion(Baseline up to approximately 91 months)
- Serum Concentration of Atezolizumab(Prior to any drug administration on Day 1 of Cycles 1, 2, 3, 4, 8, 12, and 16, and 30 minutes after end of atezolizumab infusion on Day 1 of Cycle 1 (each cycle is 21 days))
- Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab(Prior to any drug administration up to approximately 33 month)
研究者
研究点 (255)
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