Radiation Therapy With Protons or Photons in Treating Patients With Liver Cancer
A Phase III Randomized Trial of Protons Versus Photons for Hepatocellular Carcinoma
3 other identifiers
interventional
186
1 country
27
Brief Summary
This phase III trial studies how well radiation therapy with protons works compared with photons in treating patients with liver cancer. Radiation therapy, such as photon therapy, uses high energy x-rays to send the radiation inside the body to the tumor while proton therapy uses a beam of proton particles. Proton therapy can stop shortly after penetrating through the tumor and may cause less damage to the surrounding healthy organs and result in better survival in patients with liver cancer.
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 Jan 2018
Longer than P75 for phase_3
27 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
June 12, 2017
CompletedFirst Posted
Study publicly available on registry
June 14, 2017
CompletedStudy Start
First participant enrolled
January 26, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2027
February 13, 2026
February 1, 2026
9.4 years
June 12, 2017
February 10, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Overall survival (OS)
Will be estimated by the Kaplan-Meier method. The distributions of OS between treatment arms will be compared using the log rank test. The final analysis will occur after at least 125 deaths have occurred and will include: tabulation of all cases entered and those excluded from the analyses with the reasons for exclusion, distributions of important prognostic baseline variables, the frequencies and severity of adverse events by treatment arm, treatment delivery compliance, observed results with respect to the primary endpoint of OS. Will be tested with a 2-sided significance level of 0.049.
From the date of randomization to the date of death due to any cause assessed up to 4 years
Treatment effect
Will be performed using the Cox proportional hazard regression model.
Up to 4 years
Secondary Outcomes (7)
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
Local progression (LP)
From the date of randomization to the date of first LP or date of last follow-up for patients without an LP event reported assessed up to 4 years
Incidence of adverse events
Up to 4 years
Fatigue
Baseline up to 6 months
Change in fatigue
Baseline up to 1 month
- +2 more secondary outcomes
Other Outcomes (1)
Overall quality of life by Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) version 4
Baseline up to 12 months
Study Arms (2)
Arm I (proton therapy)
EXPERIMENTALPatients undergo proton therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
Arm II (photon therapy)
EXPERIMENTALPatients undergo photon therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.
Interventions
Undergo blood sample collection
Undergo CT scan
Undergo MRI
Ancillary studies
Undergo proton therapy
Eligibility Criteria
You may qualify if:
- 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
- +3 more criteria
You may not qualify if:
- 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
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NRG Oncologylead
- National Cancer Institute (NCI)collaborator
Study Sites (27)
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
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
Maryland Proton Treatment Center
Baltimore, Maryland, 21201, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Corewell Health Dearborn Hospital
Dearborn, Michigan, 48124, United States
Corewell Health William Beaumont University Hospital
Royal Oak, Michigan, 48073, United States
Corewell Health Beaumont Troy Hospital
Troy, Michigan, 48085, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
New York Proton Center
New York, New York, 10035, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
University of Washington Medical Center - Montlake
Seattle, Washington, 98195, United States
Related Publications (1)
Duda DG. Targeting Tumor Microenvironment in Liver Cancers: Rationale, Current Progress, and Future Perspective. Keio J Med. 2022;71(3):71. doi: 10.2302/kjm.71-004-ABST.
PMID: 36155490DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Theodore S Hong
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
June 12, 2017
First Posted
June 14, 2017
Study Start
January 26, 2018
Primary Completion (Estimated)
June 30, 2027
Study Completion (Estimated)
June 30, 2027
Last Updated
February 13, 2026
Record last verified: 2026-02