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Comparing proton and photon radiation therapy for liver cancer treatment

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

PHASE3 · NRG Oncology · NCT03186898

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

PhasePHASE3
Study typeInterventional
Enrollment186 (estimated)
Ages18 Years and up
SexAll
SponsorNRG Oncology (other)
Drugs / interventionschemotherapy, radiation
Locations26 sites (Atlanta, Georgia and 25 other locations)
Trial IDNCT03186898 on ClinicalTrials.gov

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.

Who should consider this trial

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

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

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

Eligibility criteria

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 this trial is running

Atlanta, Georgia and 25 other locations

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: Recurrent Hepatocellular Carcinoma, Stage III Hepatocellular Carcinoma AJCC v7, Unresectable Hepatocellular Carcinoma

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.