Testing Immunotherapy With or Without Stereotactic Body Radiation Therapy in Patients With Advanced Liver Cancer, HELIO-RT Trial
- Conditions
- Advanced Hepatocellular CarcinomaStage III Hepatocellular Carcinoma AJCC v8Stage IV Hepatocellular Carcinoma AJCC v8
- Interventions
- Procedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: Magnetic Resonance ImagingProcedure: Positron Emission TomographyOther: Questionnaire AdministrationRadiation: Stereotactic Body Radiation Therapy
- Registration Number
- NCT07166406
- Lead Sponsor
- NRG Oncology
- Brief Summary
This phase III trial compares the effect 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. Durvalumab and tremelimumab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). IO with monoclonal antibodies, such as 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.
- Detailed Description
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.
VII. To evaluate and compare liver decompensation per modified albumin-bilirubin (ALBI) (mALBI) score between treatment arms.
HEALTH-RELATED QUALITY OF LIFE (HRQOL) OBJECTIVES:
I. To compare Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) total score at 6 months between the treatment arms. (Primary) II. To evaluate and compare quality-adjusted survival using European Quality of Life Five Dimension (EQ-5D) between treatment arms. (Secondary) III. To evaluate FACT-Hep total scores over time between the treatment arms. (Exploratory)
EXPLORATORY OBJECTIVES:
I. Biospecimen collection for future correlative analyses.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients receive 1 of 3 IO-based systemic treatments per physicians decision.
TREATMENT A: Patients receive atezolizumab and bevacizumab intravenously (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.
ARM 2: Patients receive 1 of 3 IO-based systemic treatments per physicians decision.
TREATMENT A: Patients undergo liver SBRT once daily (QD), once every other day (QOD), or twice weekly for 5 fractions over up to 3 weeks. Patients also receive atezolizumab and bevacizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
TREATMENT B: Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive tremelimumab IV once and durvalumab IV every 4 weeks in the absence of disease progression or unacceptable toxicity.
TREATMENT C: Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. 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 computed tomography (CT) and CT and/or magnetic resonance imaging (MRI) throughout the study and may also undergo positron emission tomography (PET)/CT prior to registration.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years then yearly.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 252
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 treatment A (atezolizumab, bevacizumab) Atezolizumab Patients receive atezolizumab and bevacizumab IV every 3 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. Arm 1 treatment A (atezolizumab, bevacizumab) Bevacizumab Patients receive atezolizumab and bevacizumab IV every 3 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. Arm 1 treatment A (atezolizumab, bevacizumab) Biospecimen Collection Patients receive atezolizumab and bevacizumab IV every 3 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. Arm 1 treatment A (atezolizumab, bevacizumab) Computed Tomography Patients receive atezolizumab and bevacizumab IV every 3 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. Arm 1 treatment A (atezolizumab, bevacizumab) Magnetic Resonance Imaging Patients receive atezolizumab and bevacizumab IV every 3 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. Arm 1 treatment A (atezolizumab, bevacizumab) Positron Emission Tomography Patients receive atezolizumab and bevacizumab IV every 3 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. Arm 1 treatment A (atezolizumab, bevacizumab) Questionnaire Administration Patients receive atezolizumab and bevacizumab IV every 3 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. Arm 1 treatment B (tremelimumab, durvalumab) Biospecimen Collection Patients receive tremelimumab IV once and durvalumab 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. Arm 1 treatment B (tremelimumab, durvalumab) Computed Tomography Patients receive tremelimumab IV once and durvalumab 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. Arm 1 treatment B (tremelimumab, durvalumab) Magnetic Resonance Imaging Patients receive tremelimumab IV once and durvalumab 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. Arm 1 treatment B (tremelimumab, durvalumab) Positron Emission Tomography Patients receive tremelimumab IV once and durvalumab 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. Arm 1 treatment B (tremelimumab, durvalumab) Questionnaire Administration Patients receive tremelimumab IV once and durvalumab 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. Arm 1 treatment B (tremelimumab, durvalumab) Tremelimumab Patients receive tremelimumab IV once and durvalumab 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. Arm 1 treatment B (tremelimumab, durvalumab) Durvalumab Patients receive tremelimumab IV once and durvalumab 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. Arm 1 treatment C (nivolumab, ipilimumab) Biospecimen Collection 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. Arm 1 treatment C (nivolumab, ipilimumab) Computed Tomography 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. Arm 1 treatment C (nivolumab, ipilimumab) Magnetic Resonance Imaging 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. Arm 1 treatment C (nivolumab, ipilimumab) Positron Emission Tomography 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. Arm 1 treatment C (nivolumab, ipilimumab) Questionnaire Administration 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. Arm 1 treatment C (nivolumab, ipilimumab) Nivolumab 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. Arm 1 treatment C (nivolumab, ipilimumab) Ipilimumab 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. Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Atezolizumab Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive atezolizumab and bevacizumab IV every 3 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. Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Bevacizumab Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive atezolizumab and bevacizumab IV every 3 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. Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Biospecimen Collection Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive atezolizumab and bevacizumab IV every 3 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. Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Computed Tomography Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive atezolizumab and bevacizumab IV every 3 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. Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Magnetic Resonance Imaging Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive atezolizumab and bevacizumab IV every 3 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. Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Positron Emission Tomography Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive atezolizumab and bevacizumab IV every 3 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. Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Questionnaire Administration Arm 2 treatment A (atezolizumab, bevacizumab, SBRT) Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive atezolizumab and bevacizumab IV every 3 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. Arm 2 treatment B (tremelimumab, durvalumab, SBRT) Biospecimen Collection Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive tremelimumab IV once and durvalumab 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. Arm 2 treatment B (tremelimumab, durvalumab, SBRT) Computed Tomography Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive tremelimumab IV once and durvalumab 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. Arm 2 treatment B (tremelimumab, durvalumab, SBRT) Magnetic Resonance Imaging Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive tremelimumab IV once and durvalumab 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. Arm 2 treatment B (tremelimumab, durvalumab, SBRT) Positron Emission Tomography Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive tremelimumab IV once and durvalumab 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. Arm 2 treatment B (tremelimumab, durvalumab, SBRT) Questionnaire Administration Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive tremelimumab IV once and durvalumab 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. Arm 2 treatment B (tremelimumab, durvalumab, SBRT) Tremelimumab Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive tremelimumab IV once and durvalumab 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. Arm 2 treatment B (tremelimumab, durvalumab, SBRT) Durvalumab Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive tremelimumab IV once and durvalumab 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. Arm 2 treatment B (tremelimumab, durvalumab, SBRT) Stereotactic Body Radiation Therapy Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. Patients also receive tremelimumab IV once and durvalumab 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. Arm 2 treatment C (nivolumab, ipilimumab, SBRT) Biospecimen Collection Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. 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. Arm 2 treatment C (nivolumab, ipilimumab, SBRT) Computed Tomography Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. 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. Arm 2 treatment C (nivolumab, ipilimumab, SBRT) Magnetic Resonance Imaging Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. 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. Arm 2 treatment C (nivolumab, ipilimumab, SBRT) Positron Emission Tomography Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. 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. Arm 2 treatment C (nivolumab, ipilimumab, SBRT) Questionnaire Administration Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. 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. Arm 2 treatment C (nivolumab, ipilimumab, SBRT) Nivolumab Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. 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. Arm 2 treatment C (nivolumab, ipilimumab, SBRT) Ipilimumab Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. 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. Arm 2 treatment C (nivolumab, ipilimumab, SBRT) Stereotactic Body Radiation Therapy Patients undergo liver SBRT QD, QOD, or twice weekly for 5 fractions over up to 3 weeks. 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.
- Primary Outcome Measures
Name Time Method Overall survival (OS) 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.
- Secondary Outcome Measures
Name Time Method 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 Will be estimated by the Kaplan-Meier method (Kaplan 1958) and estimates between treatment arms will be compared using the log-rank test (Mantel 1966). The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with PFS (Cox 1972).
Objective response rate (ORR) Up to 4 years Will be defined as having a complete or partial response. ORR will be compared between treatment arms using a chi-squared test. Duration of response will also be reported.
Vascular recanalization (VR) Up to 4 years Will be defined as having a complete or partial vascular thrombosis response. The VR proportion for each treatment arm will be determined and compared between treatment arms using a chi-squared test. Time to best VR response before progression and duration of VR response will be reported, but no statistical testing will be done.
Incidence of grade >= 4 adverse events (AEs) (Experimental arm Up to 90 days from randomization Will be compared between the treatment arms using a Z-test.
Safety of stereotactic body radiation therapy with immunotherapy-based systemic therapy Up to 90 days from randomization Will be defined as grade \>= 4 AEs definitely related to protocol treatment. Will be compared between the treatment arms using a Z-test.
Selected long-term treatment-related toxicity Up to 18 months after randomization Will focus on grade \>=4 hepatobiliary or gastrointestinal AEs and any grade 5 AE. The percentage of patients with the above-specified treatment related AEs will be compared between the treatment arms using a Z-test.
Biochemical decline in alpha-fetoprotein (BD-AFP) Up to 4 years Will be defined as a ≥ 20% decrease in AFP from baseline. The BD-AFP proportion for each treatment arm will be determined and compared between treatment arms using a chi-squared test.
Liver decompensation rate per Child Pugh score (LDR-CP) Up to 4 years The LDR-CP proportion for each treatment arm will be determined and compared between treatment arms using a chi-squared test.
Liver decompensation rate per modified albumin-bilirubin (ALBI) score (LDR-mALBI) Up to 4 years The LDR-mALBI proportion for each treatment arm will be determined and compared between treatment arms using a chi-squared test.