A Phase II, Open-label, Multi-cohort, Multicenter Study in Patients With Unresectable Hepatocellular Carcinoma and Child-pugh B7 and B8 Cirrhosis
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 30
- 试验地点
- 111
- 主要终点
- Percentage of Participants With Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to assess the safety of atezolizumab and bevacizumab, or atezolizumab alone, as first-line treatment in participants with unresectable, locally advanced or metastatic hepatocellular carcinoma (HCC) with Child-pugh B7 or B8 cirrhosis.
详细描述
This is a Phase II, open-label, multicohort, multicenter study in participants with unresectable, locally advanced, or metastatic HCC who have Child-pugh B7 or B8 liver cirrhosis and have received no prior systemic therapy in this treatment setting. The study is designed to non-comparatively evaluate the safety of atezolizumab plus bevacizumab (Cohort A) or atezolizumab monotherapy (Cohort B) in this population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •General Inclusion Criteria:
- •Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants
- •Disease that is not amenable to curative surgical and/or locoregional therapies
- •No prior systemic treatment (including systemic investigational agents) for locally advanced or metastatic and/or unresectable HCC
- •Measurable disease (at least one untreated target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 7 days prior to initiation of study treatment
- •Child-pugh B7 or B8 cirrhosis at screening and within 7 days prior to study treatment
- •Adequate hematologic and end-organ function
- •Life expectancy of at least 12 weeks
- •Female participants of childbearing potential must be willing to avoid pregnancy and egg donation
- •Absolute neutrophil count ≥1.0 x 10^9 per liter (/L) (≥1000 per microliter [/μL]) without granulocyte colony-stimulating factor support
- •Platelet count ≥ 50 × 109/L (50,000/μL) without transfusion
- •Hemoglobin ≥ 80 grams per liter (g/L) (8 grams per deciliter [g/dL]) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × upper limit of normal (ULN)
- •Serum bilirubin ≤ 3 × ULN
- •Creatinine clearance ≥ 50 milliliters per minute (mL/min) (calculated using the Cockcroft-gault formula)
- •Serum albumin ≥ 20 g/L (2.0 g/dL) without transfusion in the prior 3 months
- •International normalized ratio (INR) ≤2.3
排除标准
- •Pregnancy or breastfeeding
- •Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies
- •Treatment with investigational therapy within 28 days prior to initiation of study treatment
- •Treatment with locoregional therapy to liver within 28 days prior to initiation of study treatment, or non-recovery from side effects of any such procedure
- •Treatment with systemic immunostimulatory agents
- •Treatment with systemic immunosuppressive medication
- •Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment
- •Inadequately controlled hypertension
- •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 computed tomography (CT) scan
- •Participants who have a known concurrent malignancy that is progressing or requires active treatment, who have not completely recovered from treatment, or who have a significant malignancy history that, in the opinion of the investigator, should preclude participation
- •Participants on preventative hormonal therapies (i.e., tamoxifen and other hormonal inhibitors) are not excluded
- •Known fibrolamellar HCC, sarcomatoid HCC, other rare HCC variant, or mixed cholangiocarcinoma and HCC
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- •Prior allogeneic stem cell or solid organ transplantation
- •Actively listed for liver transplantation
- •Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV)
- •Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding
- •A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
- •Grade ≥3 hemorrhage or bleeding event within 6 months prior to initiation of study treatment
- •Hepatic encephalopathy is allowed if no active symptoms or stable within 3 months of study treatment
- •History, planned, or recommended placement of transjugular intrahepatic portosystemic shunt (TIPS) is excluded from Cohort A only. TIPS is acceptable in Cohort B
- •Diagnostic paracentesis is allowed. Therapeutic paracentesis: one large volume paracentesis prior to enrollment with diuretic controlled ascites is allowed.
- •Participants with ascites controlled on diuretics are allowed
- •History of spontaneous bacterial peritonitis within last 12 months
研究组 & 干预措施
Cohort B: Atezolizumab
Participants will receive atezolizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator.
干预措施: Atezolizumab (Drug)
Cohort A: Atezolizumab+Bevacizumab
Participants will receive atezolizumab plus bevacizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator.
干预措施: Atezolizumab (Drug)
Cohort A: Atezolizumab+Bevacizumab
Participants will receive atezolizumab plus bevacizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events (AEs)
时间窗: Baseline through the end of the study (up to approximately 36 months)
An AE is any untoward medical occurrence in a participant or clinical study participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Severity is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) in Cohorts A and B.
次要结局
未报告次要终点