Phase III Randomized Trial of IO-Based Systemic Treatment +/- Liver SBRT in Hepatocellular Cancer With Macrovascular Invasion (HELIO-RT)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- NRG Oncology
- 入组人数
- 226
- 试验地点
- 139
- 主要终点
- Overall survival (OS)
研究概览
简要总结
This phase III trial compares the effect of immunotherapy (IO) with stereotactic body radiation therapy (SBRT) to IO alone in treating patients with liver cancer (hepatocellular cancer) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). The usual approach is treatment with IO-based drug combinations, such as atezolizumab and bevacizumab, durvalumab and tremelimumab, or ipilimumab and nivolumab. IO with monoclonal antibodies, such as durvalumab, tremelimumab, atezolizumab, nivolumab and ipilimumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor cells. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Giving IO with SBRT may be more effective than IO alone in helping patients with advanced hepatocellular cancer live longer.
详细描述
PRIMARY OBJECTIVE:
I. To determine if liver SBRT in combination with IO-based systemic therapy improves survival compared to IO-based systemic therapy alone, in patients with hepatocellular cancer with macrovascular invasion.
SECONDARY OBJECTIVES:
I. To evaluate and compare progression-free survival between treatment arms. II. To evaluate and compare objective response rate between treatment arms. III. To evaluate and compare vascular recanalization between treatment arms. IV. To evaluate and compare biochemical decline in alpha-fetoprotein (AFP) between treatment arms.
V. To evaluate and compare toxicity within and between treatment arms. VI. To evaluate and compare liver decompensation per Child Pugh score between treatment arms.
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
盲法说明
No Data Available
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
- •PRIOR TO STEP 1 REGISTRATION:
- •Diagnosis of hepatocellular carcinoma (HCC) by at least 1 criterion listed below:
- •Pathologically (histologically or cytologically) proven diagnosis of HCC (strongly recommended)
- •Radiographically proven (American Association for the Study of Liver Diseases [AASLD] criteria) diagnosis of HCC by multiphasic MRI and/or CT scan is allowed.
- •For patients with a prior or concurrent malignancy, pathologic confirmation of hepatocellular cancer is required.
- •HCC macrovascular invasion, defined as enhancing vascular thrombosis demonstrating arterial enhancement and venous or delayed venous washout on multiphasic MRI and/or CT is required.
- •Presence of extrahepatic metastatic disease on CT chest and CT or MRI pelvis, or PET/CT chest/abdomen/pelvis is permitted.
- •5 or fewer discrete intrahepatic parenchymal foci of HCC.
- •Total maximal sum of hepatocellular carcinoma tumors, as a single conglomerate, multiple lesions, or infiltrative HCC < 20 cm in total summed diameter.
- •No direct primary tumor extension into the stomach, duodenum, small bowel, or large bowel.
- •No known fibrolamellar HCC, sarcomatoid HCC, or biphenotypic HCC.
- •Child-Pugh class A or B7 liver function.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Not pregnant and not nursing
- •Negative urine or serum pregnancy test (in persons of childbearing potential) within 30 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal.
- •Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^
- •Platelets ≥ 60,000 cells/mm^
- •Hemoglobin ≥ 8g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] ≥ 8g/dl is acceptable).
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 6 x institutional upper limit of normal (ULN).
- •Total bilirubin < 4 x institutional ULN.
- •Creatinine clearance (CrCL) ≥ 30 mL/min/1.73 m^2 by the Cockcroft-Gault formula.
- •For treatment of HCC:
- •Prior surgical resection, transarterial chemoembolization (TACE), and ablation are permitted.
- •No prior systemic therapy or transarterial radioembolization (TARE) for HCC.
- •No history of liver transplantation.
- •For prior treatment for any malignancy:
- •Prior systemic therapy for a different cancer is allowable, except for prior immunotherapy.
- •No prior radiotherapy to the region of the study cancer that would result in significant overlap of radiation therapy fields that would lead to excessive cumulative toxicity at the discretion of the investigator.
- •No medical contraindication to the standard of care immunotherapy.
- •For patients to be treated with atezolizumab/bevacizumab:
- •No history of a gastrointestinal (GI) bleed or other clinically significant bleeding event within 6 months prior to study registration.
- •Systemic immunostimulatory agents (including, but not limited to, interferons and interleukin-2 [IL-2]) are prohibited within 4 weeks or five drug elimination half-lives (whichever is longer) prior to registration and during the study period.
- •No history of allergic reaction to the systemic therapy agent(s), compounds of similar chemical or biologic composition to the systemic therapy agent(s) (or any of its excipients).
- •PRIOR TO STEP 2 RANDOMIZATION:
- •Obtain confirmation of payment coverage (insurance or other) for both possible treatment arms.
排除标准
- 未提供
研究组 & 干预措施
Arm 1 (IO-based systemic therapy alone [Treatment A/B/C])
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Biospecimen Collection (Procedure)
Arm 1 (IO-based systemic therapy alone [Treatment A/B/C])
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Computed Tomography (Procedure)
Arm 1 (IO-based systemic therapy alone [Treatment A/B/C])
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm 1 (IO-based systemic therapy alone [Treatment A/B/C])
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Questionnaire Administration (Other)
Arm 2 (SBRT + IO-based systemic therapy [Treatment A/B/C])
Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks in addition to one of the treatment regimens described below.
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Biospecimen Collection (Procedure)
Arm 2 (SBRT + IO-based systemic therapy [Treatment A/B/C])
Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks in addition to one of the treatment regimens described below.
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Computed Tomography (Procedure)
Arm 2 (SBRT + IO-based systemic therapy [Treatment A/B/C])
Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks in addition to one of the treatment regimens described below.
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm 2 (SBRT + IO-based systemic therapy [Treatment A/B/C])
Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks in addition to one of the treatment regimens described below.
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Questionnaire Administration (Other)
Arm 2 (SBRT + IO-based systemic therapy [Treatment A/B/C])
Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks in addition to one of the treatment regimens described below.
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Stereotactic Body Radiation Therapy (Radiation)
Arm 1 (IO-based systemic therapy alone [Treatment A/B/C])
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Durvalumab (Biological)
Arm 1 (IO-based systemic therapy alone [Treatment A/B/C])
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Ipilimumab (Biological)
Arm 1 (IO-based systemic therapy alone [Treatment A/B/C])
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Nivolumab (Biological)
Arm 1 (IO-based systemic therapy alone [Treatment A/B/C])
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Tremelimumab (Biological)
Arm 1 (IO-based systemic therapy alone [Treatment A/B/C])
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Bevacizumab (Biological)
Arm 1 (IO-based systemic therapy alone [Treatment A/B/C])
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Atezolizumab (Biological)
Arm 2 (SBRT + IO-based systemic therapy [Treatment A/B/C])
Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks in addition to one of the treatment regimens described below.
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Bevacizumab (Biological)
Arm 2 (SBRT + IO-based systemic therapy [Treatment A/B/C])
Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks in addition to one of the treatment regimens described below.
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Durvalumab (Biological)
Arm 2 (SBRT + IO-based systemic therapy [Treatment A/B/C])
Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks in addition to one of the treatment regimens described below.
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Atezolizumab (Biological)
Arm 2 (SBRT + IO-based systemic therapy [Treatment A/B/C])
Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks in addition to one of the treatment regimens described below.
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Ipilimumab (Biological)
Arm 2 (SBRT + IO-based systemic therapy [Treatment A/B/C])
Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks in addition to one of the treatment regimens described below.
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Nivolumab (Biological)
Arm 2 (SBRT + IO-based systemic therapy [Treatment A/B/C])
Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks in addition to one of the treatment regimens described below.
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Tremelimumab (Biological)
Arm 2 (SBRT + IO-based systemic therapy [Treatment A/B/C])
Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks in addition to one of the treatment regimens described below.
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Positron Emission Tomography (Procedure)
Arm 1 (IO-based systemic therapy alone [Treatment A/B/C])
Treatment A: Patients receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment B: Patients receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment C: Patients receive nivolumab and ipilimumab IV every 3 weeks for up to 4 doses followed by nivolumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood sample collection, chest CT and CT and/or MRI throughout the study and may also undergo PET/CT prior to registration.
干预措施: Positron Emission Tomography (Procedure)
结局指标
主要结局
Overall survival (OS)
时间窗: From the date of randomization to the date of death or last follow-up, assessed up to 4 years
Will be estimated by the Kaplan-Meier method (Kaplan 1958). The distributions of the OS estimates between the two arms will be compared using a log-rank test. The Cox regression model will be used to analyze the effects of factors, in addition to treatment, including, but not limited to stratification factors, which may be associated with OS.
Overall survival (OS)
时间窗: From the date of randomization to the date of death or last follow-up, assessed up to 5 years
Will be estimated by the Kaplan-Meier method (Kaplan 1958). The distributions of the OS estimates between the two arms will be compared using a log-rank test. The Cox regression model will be used to analyze the effects of factors, in addition to treatment, including, but not limited to stratification factors, which may be associated with OS. The primary analysis will happen after at least 150 OS events (deaths) have occurred and will be tested with a 1-sided significance level of 0.022 (level based on not having stopped at either of the 2 planned interim analyses).
次要结局
- Progression-free survival (PFS)(From the date of randomization to the date of first PFS failure or last follow-up for patients without a reported PFS event, assessed up to 4 years)
- Objective response rate (ORR)(Up to 4 years)
- Vascular recanalization (VR)(Up to 4 years)
- Incidence of grade >= 4 adverse events (AEs) (Experimental arm(Up to 90 days from randomization)
- Safety of stereotactic body radiation therapy with immunotherapy-based systemic therapy(Up to 90 days from randomization)
- Biochemical decline in alpha-fetoprotein (BD-AFP)(Up to 4 years)
- Liver decompensation rate per Child Pugh score (LDR-CP)(Up to 4 years)
- Liver decompensation rate per modified albumin-bilirubin (ALBI) score (LDR-mALBI)(Up to 4 years)
- Selected long-term treatment-related toxicity(Up to 18 months after randomization)
- Progression-free survival (PFS)(From the date of randomization to the date of first PFS failure or last follow-up for patients without a reported PFS event, assessed up to 5 years)
- Objective response rate (ORR)(Up to 5 years)
- Vascular recanalization (VR)(Up to 5 years)
- Short-term toxicity(Up to 90 days from randomization)
- Biochemical decline in alpha-fetoprotein (BD-AFP)(Up to 5 years)
- Liver decompensation rate per Child Pugh score (LDR-CP)(Up to 5 years)
- Liver decompensation rate per modified albumin-bilirubin (ALBI) score (LDR-mALBI)(Up to 5 years)