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Immunotherapy with or without targeted high-dose liver radiation (SBRT) for advanced liver cancer

Phase III Randomized Trial of IO-Based Systemic Treatment +/- Liver SBRT in Hepatocellular Cancer With Macrovascular Invasion (HELIO-RT)

PHASE3 · NRG Oncology · NCT07166406

This trial will see if adding targeted high-dose liver radiation (SBRT) to standard immunotherapy helps people with advanced liver cancer that has invaded blood vessels.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment226 (estimated)
Ages18 Years and up
SexAll
SponsorNRG Oncology (other)
Drugs / interventionsatezolizumab, bevacizumab, immunotherapy, radiation, durvalumab, tremelimumab, ipilimumab, nivolumab
Locations107 sites (Berkeley, California and 106 other locations)
Trial IDNCT07166406 on ClinicalTrials.gov

What this trial studies

This Phase III randomized trial compares standard immunotherapy-based systemic treatment alone versus the same immunotherapy combined with stereotactic body radiation therapy (SBRT) to the liver in patients with hepatocellular carcinoma (HCC) with macrovascular invasion. Standard immunotherapy regimens may include combinations such as atezolizumab plus bevacizumab, durvalumab plus tremelimumab, or ipilimumab plus nivolumab. Primary outcome is overall survival, with secondary endpoints including progression-free survival, objective response rate, vascular recanalization, AFP decline, toxicity, liver decompensation measures, and quality of life; biospecimens will be collected for exploratory correlative studies. Participants are limited to patients meeting HCC diagnostic criteria with macrovascular invasion and a defined number/size of intrahepatic lesions, and extrahepatic disease is permitted per protocol.

Who should consider this trial

Good fit: Adults with hepatocellular carcinoma showing macrovascular invasion, up to five discrete intrahepatic lesions (per protocol limits), and adequate liver function who are eligible for immunotherapy are the intended participants.

Not a fit: Patients with decompensated liver disease, disease burden exceeding the trial's intrahepatic limits, or tumors that do not meet the macrovascular invasion criteria are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding SBRT to immunotherapy could extend survival, improve tumor shrinkage, and help reopen blood vessels blocked by tumor, potentially delaying liver failure.

How similar studies have performed: Early-phase trials and retrospective series have suggested that combining SBRT with immunotherapy can improve local control and response rates, but definitive large randomized phase III evidence is not yet available.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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.
* Age ≥ 18.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
* 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\^3.
* Platelets ≥ 60,000 cells/mm\^3.
* 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.

Where this trial is running

Berkeley, California and 106 other locations

+57 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Advanced Hepatocellular Carcinoma, Stage III Hepatocellular Carcinoma AJCC v8, Stage IV Hepatocellular Carcinoma AJCC v8

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.