Clinical trial No longer in our active list Phase 3 Interventional Ages 18 and up

Comparing proton and photon radiation therapy for liver cancer treatment

Official title: A Phase III Randomized Trial of Protons Versus Photons for Hepatocellular Carcinoma

Run by NRG Oncology · NCT03186898 · Data updated 2026-05-14

This study is no longer in our active list. It may have stopped recruiting or finished. The details below are as of 2026-05-14 and are kept for reference. Check ClinicalTrials.gov for its current status, or see similar studies below.

This study is testing whether proton therapy works better than photon therapy for treating liver cancer by looking at how long patients live and how well they feel during treatment.

Quick facts

PhasePhase 3
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment186 (estimated)
SponsorNRG Oncology
Academic / other
Drugs / interventionschemotherapy, radiation
Locations26 sites (Atlanta, Georgia and 25 other locations)
Trial IDNCT03186898 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Ideal candidates include patients with unresectable or locally recurrent hepatocellular carcinoma who have measurable disease.

Probably not a fit

Patients with resectable liver cancer or those with extensive disease beyond the eligibility criteria may not benefit from this study.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase III trial investigates the effectiveness of proton therapy versus photon therapy in treating patients with liver cancer, specifically focusing on overall survival and progression-free survival rates. Patients will be randomly assigned to receive either proton therapy or photon therapy over a period of 15-24 days. The study also aims to assess differences in local progression, toxicity, fatigue, and quality of life between the two treatment groups. Additionally, biospecimens will be collected for future research.

Why it matters

Potential benefit: If successful, this study could lead to improved survival rates and quality of life for patients with liver cancer.

How similar studies have gone: Other studies have shown promising results with proton therapy in various cancers, suggesting potential benefits in this novel application for liver cancer.

Who can join: the full rules

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Pathologically (histologically or cytologically) or radiographically-proven (based on the American Association for the Study of Liver Diseases \[AALSD\] criteria) unresectable or locally recurrent hepatocellular cancer prior to registration
* Appropriate stage for study entry based on the following diagnostic workup:

  * All patients must have computed tomography (CT) scan chest/abdomen/pelvis with multiphasic liver CT scan prior to registration; if CT contrast is contraindicated, CT chest without contrast and magnetic resonance imaging (MRI) of abdomen is permitted
  * Participants must have measurable disease at study entry, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> 2 cm with conventional techniques or as \> 1 cm with spiral CT scan
  * Patient must have 3 or fewer single or multinodular tumors; for patients with a single lesion, lesion must be 15 cm or less in greatest dimension; for patients with two lesions, no lesion may be greater than 10 cm in greatest dimension; for patients with three lesions, no lesion may be greater than 6 cm in greatest dimension; portal vein involvement or thrombosis combined with a single lesion that is \>= 1 cm and =\< 15 cm in greatest dimension is allowed
* Age \>= 18
* Zubrod performance status 0-1 within 30 days prior to registration
* Negative urine or serum pregnancy test for women of childbearing potential within 7 days prior to study entry
* Absolute neutrophil count (ANC) \>= 1,000 cells/mm\^3
* Platelets \>= 50,000 cells/mm\^3
* Hemoglobin \>= 9.0 g/dl; (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 9.0 g/dl is acceptable)
* Total bilirubin \< 4 x institutional upper limit of normal (ULN)
* Transaminases (aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\]) \< 6 x institutional ULN
* Albumin \>= 2.5 g/dl
* Creatinine \< 2 mg/dl
* Prior chemotherapy, targeted biological therapy (e.g. sorafenib), surgery, transarterial chemoembolization (TACE), ablation for present disease is acceptable
* Must have Child-Turcotte-Pugh (CTP) A or B7
* The patient or a legally authorized representative must provide study-specific informed consent prior to study registration

Exclusion Criteria:

* PRIOR TO STEP ONE REGISTRATION:
* Definitive clinical or radiologic documentation of extrahepatic tumor, defined as extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) \> 3.0 cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastatic lymph node or two 2 cm lung lesions); note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is \> 2.0 cm
* Uncontrolled prior invasive malignancy, excluding the current diagnosis
* Systemic chemotherapy for the study cancer \< 2 weeks prior to registration
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
* HIV positive with CD4 count \< 200 cells/microliter; note that patients who are human immunodeficiency virus (HIV) positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count \>= 200 cells/microliter prior to registration; note also that HIV testing is not required for eligibility for this protocol; this exclusion criterion is necessary because the treatments involved in this protocol may be significantly immunosuppressive
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields (to include Y90)
* Prior liver transplant
* PRIOR TO STEP TWO RANDOMIZATION:
* Unable to obtain confirmation of payment coverage (insurance or other) for either possible treatment

Where it's running

  • Emory Proton Therapy Center
    Atlanta, Georgia, United States
    Recruiting
  • Emory University Hospital Midtown
    Atlanta, Georgia, United States
    Recruiting
  • Emory University Hospital/Winship Cancer Institute
    Atlanta, Georgia, United States
    Recruiting
  • Emory Saint Joseph's Hospital
    Atlanta, Georgia, United States
    Recruiting
  • Maryland Proton Treatment Center
    Baltimore, Maryland, United States
    Recruiting
  • University of Maryland/Greenebaum Cancer Center
    Baltimore, Maryland, United States
    Recruiting
Show 20 more locations
  • Massachusetts General Hospital Cancer Center
    Boston, Massachusetts, United States
    Recruiting
  • Corewell Health Dearborn Hospital
    Dearborn, Michigan, United States
    Recruiting
  • Corewell Health William Beaumont University Hospital
    Royal Oak, Michigan, United States
    Recruiting
  • Corewell Health Beaumont Troy Hospital
    Troy, Michigan, United States
    Recruiting
  • Washington University School of Medicine
    Saint Louis, Missouri, United States
    Recruiting
  • New York Proton Center
    New York, New York, United States
    Recruiting
  • University of Cincinnati Cancer Center-UC Medical Center
    Cincinnati, Ohio, United States
    Recruiting
  • Case Western Reserve University
    Cleveland, Ohio, United States
    Recruiting
  • University of Cincinnati Cancer Center-West Chester
    West Chester, Ohio, United States
    Recruiting
  • M D Anderson Cancer Center
    Houston, Texas, United States
    Recruiting
  • Fred Hutchinson Cancer Center
    Seattle, Washington, United States
    Recruiting
  • University of Washington Medical Center - Montlake
    Seattle, Washington, United States
    Recruiting
  • Northwestern Medicine Cancer Center Warrenville
    Warrenville, Illinois, United States
    Active not recruiting
  • Memorial Sloan Kettering Basking Ridge
    Basking Ridge, New Jersey, United States
    Active not recruiting
  • Memorial Sloan Kettering Monmouth
    Middletown, New Jersey, United States
    Active not recruiting
  • Memorial Sloan Kettering Bergen
    Montvale, New Jersey, United States
    Active not recruiting
  • Memorial Sloan Kettering Commack
    Commack, New York, United States
    Active not recruiting
  • Memorial Sloan Kettering Westchester
    Harrison, New York, United States
    Active not recruiting
  • Memorial Sloan Kettering Cancer Center
    New York, New York, United States
    Active not recruiting
  • Memorial Sloan Kettering Nassau
    Uniondale, New York, United States
    Active not recruiting

Study contacts

  • Principal investigator: Theodore S Hong — NRG Oncology

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 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.