Testing Immunotherapy With or Without Stereotactic Body Radiation Therapy in Patients With Advanced Liver Cancer, HELIO-RT Trial
Phase III Randomized Trial of IO-Based Systemic Treatment +/- Liver SBRT in Hepatocellular Cancer With Macrovascular Invasion (HELIO-RT)
3 other identifiers
interventional
226
1 country
107
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Feb 2026
Typical duration for phase_3
107 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 3, 2025
CompletedFirst Posted
Study publicly available on registry
September 10, 2025
CompletedStudy Start
First participant enrolled
February 26, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 10, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 10, 2029
May 4, 2026
April 1, 2026
3 years
September 3, 2025
April 28, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Overall survival (OS)
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).
From the date of randomization to the date of death or last follow-up, assessed up to 5 years
Secondary Outcomes (8)
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
Selected long-term treatment-related toxicity
Up to 18 months after randomization
- +3 more secondary outcomes
Other Outcomes (6)
Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) mean total score at 6 Months
At 6 months
FACT-Hep total score over time
At baseline and at 3, 6, and 12 months from randomization
Quality-adjusted survival
At baseline and at 3, 6, and 12 months post treatment completion
- +3 more other outcomes
Study Arms (2)
Arm 1 (IO-based systemic therapy alone [Treatment A/B/C])
ACTIVE COMPARATORTreatment 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.
Arm 2 (SBRT + IO-based systemic therapy [Treatment A/B/C])
EXPERIMENTALPatients 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.
Interventions
Given IV
Given IV
Undergo blood sample collection
Given IV
Undergo MRI
Given IV
Undergo PET/CT
Undergo liver SBRT
Given IV
Undergo CT and PET/CT
Given IV
Ancillary studies
Eligibility Criteria
You may qualify if:
- 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.
- 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.
- Age ≥ 18.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Not pregnant and not nursing
- +21 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NRG Oncologylead
Study Sites (107)
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, 94704, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
Cameron Park, California, 95682, United States
Palo Alto Medical Foundation-Fremont
Fremont, California, 94538, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
Palo Alto Medical Foundation-Camino Division
Mountain View, California, 94040, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Palo Alto Medical Foundation Health Care
Palo Alto, California, 94301, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville, California, 95661, United States
Sutter Roseville Medical Center
Roseville, California, 95661, United States
Sutter Medical Center Sacramento
Sacramento, California, 95816, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
California Pacific Medical Center-Pacific Campus
San Francisco, California, 94115, United States
Sutter Pacific Medical Foundation
Santa Rosa, California, 95403, United States
Palo Alto Medical Foundation-Sunnyvale
Sunnyvale, California, 94086, United States
Poudre Valley Hospital
Fort Collins, Colorado, 80524, United States
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, 80528, United States
Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado, 81501, United States
UCHealth Greeley Hospital
Greeley, Colorado, 80631, United States
Medical Center of the Rockies
Loveland, Colorado, 80538, United States
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, 06418, United States
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, 06824, United States
Smilow Cancer Hospital Care Center at Glastonbury
Glastonbury, Connecticut, 06033, United States
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut, 06830, United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437, United States
Smilow Cancer Hospital-Hamden Care Center
Hamden, Connecticut, 06518, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510, United States
Yale University
New Haven, Connecticut, 06520, United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, 06473, United States
Smilow Cancer Hospital Care Center at Long Ridge
Stamford, Connecticut, 06902, United States
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut, 06790, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611, United States
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut, 06708, United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, 06385, United States
Grady Health System
Atlanta, Georgia, 30303, United States
Emory Proton Therapy Center
Atlanta, Georgia, 30308, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
UChicago Medicine Northwest Indiana
Crown Point, Indiana, 46307, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023, United States
Mercy Cancer Center-West Lakes
Clive, Iowa, 50325, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325, United States
Greater Regional Medical Center
Creston, Iowa, 50801, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309, United States
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263, United States
Mercy Medical Center-West Lakes
West Des Moines, Iowa, 50266, United States
The Iowa Clinic PC
West Des Moines, Iowa, 50266, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183, United States
Henry Ford Medical Center-Fairlane
Dearborn, Michigan, 48126, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Allegiance Health
Jackson, Michigan, 49201, United States
Henry Ford Medical Center-Columbus
Novi, Michigan, 48377, United States
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, 48322, United States
Henry Ford Wyandotte Hospital
Wyandotte, Michigan, 48192, United States
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, 56401, United States
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636, United States
Essentia Health Cancer Center
Duluth, Minnesota, 55805, United States
Essentia Health Saint Mary's Medical Center
Duluth, Minnesota, 55805, United States
Miller-Dwan Hospital
Duluth, Minnesota, 55805, United States
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746, United States
Essentia Health Sandstone
Sandstone, Minnesota, 55072, United States
Essentia Health Virginia Clinic
Virginia, Minnesota, 55792, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106, United States
Mount Sinai Hospital
New York, New York, 10029, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Clackamas Radiation Oncology Center
Clackamas, Oregon, 97015, United States
Providence Newberg Medical Center
Newberg, Oregon, 97132, United States
Providence Willamette Falls Medical Center
Oregon City, Oregon, 97045, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Providence Saint Vincent Medical Center
Portland, Oregon, 97225, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania, 17837, United States
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711, United States
Inova Alexandria Hospital
Alexandria, Virginia, 22304, United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031, United States
Inova Fair Oaks Hospital
Fairfax, Virginia, 22033, United States
Inova Fairfax Hospital
Falls Church, Virginia, 22042, United States
Inova Loudoun Hospital
Leesburg, Virginia, 20176, United States
Duluth Clinic Ashland
Ashland, Wisconsin, 54806, United States
Northwest Wisconsin Cancer Center
Ashland, Wisconsin, 54806, United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701, United States
Essentia Health-Hayward Clinic
Hayward, Wisconsin, 54843, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
ProHealth D N Greenwald Center
Mukwonago, Wisconsin, 53149, United States
ProHealth Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin, 53066, United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868, United States
Essentia Health-Spooner Clinic
Spooner, Wisconsin, 54801, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482, United States
Essentia Health Saint Mary's Hospital - Superior
Superior, Wisconsin, 54880, United States
UW Cancer Center at ProHealth Care
Waukesha, Wisconsin, 53188, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jennifer Y Wo
NRG Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 3, 2025
First Posted
September 10, 2025
Study Start
February 26, 2026
Primary Completion (Estimated)
March 10, 2029
Study Completion (Estimated)
March 10, 2029
Last Updated
May 4, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.