Radiation Therapy With Protons or Photons in Treating Patients With Liver Cancer

NCT ID: NCT03186898

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

186 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-26

Study Completion Date

2027-06-30

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVE:

I. To determine if overall survival (OS) is different for hepatocellular carcinoma patients treated with protons compared to photons.

SECONDARY OBJECTIVES:

I. To determine the difference in progression-free-survival (PFS) in patients with hepatocellular carcinoma (HCC) treated with protons compared to patients with HCC treated with photons.

II. To determine the difference in local progression (LP) in patients with HCC treated with protons compared to patients with HCC treated with photons.

III. To determine differences in toxicity in patients with HCC treated with protons versus photons.

IV. To determine differences in fatigue, as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue in patients with HCC treated with protons, versus photons; as well as quality-adjusted survival, if the primary endpoint is met.

V. To determine if there are correlations between the baseline values of hepatocyte growth factor (HGF) and outcomes (OS/PFS/fatigue).

EXPLORATORY OBJECTIVES:

I. To determine differences in overall quality of life, measured by Functional Assessment of Cancer Therapy-Hepatobiliary Cancer (FACT-Hep) in patients with HCC treated with protons.

II. Biospecimen collection for future correlative science projects.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo proton therapy over 15-24 days for 5 or 15 fractions.

ARM II: Patients undergo photon therapy over 15-24 days for 5 or 15 fractions.

Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI) and blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for up to 5 years.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I (proton therapy)

Patients undergo proton therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Radiation Therapy

Intervention Type RADIATION

Undergo proton therapy

Arm II (photon therapy)

Patients undergo photon therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Radiation Therapy

Intervention Type RADIATION

Undergo photon therapy

Interventions

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Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT scan

Intervention Type PROCEDURE

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Radiation Therapy

Undergo proton therapy

Intervention Type RADIATION

Radiation Therapy

Undergo photon therapy

Intervention Type RADIATION

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan tomography Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Quality of Life Assessment Cancer Radiotherapy Energy Type ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation Cancer Radiotherapy Energy Type ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

NRG Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Theodore S Hong

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

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Emory Proton Therapy Center

Atlanta, Georgia, United States

Site Status RECRUITING

Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status RECRUITING

Emory Saint Joseph's Hospital

Atlanta, Georgia, United States

Site Status RECRUITING

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States

Site Status ACTIVE_NOT_RECRUITING

Maryland Proton Treatment Center

Baltimore, Maryland, United States

Site Status RECRUITING

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status RECRUITING

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status RECRUITING

Corewell Health Dearborn Hospital

Dearborn, Michigan, United States

Site Status RECRUITING

Corewell Health William Beaumont University Hospital

Royal Oak, Michigan, United States

Site Status RECRUITING

Corewell Health Beaumont Troy Hospital

Troy, Michigan, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status ACTIVE_NOT_RECRUITING

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Site Status ACTIVE_NOT_RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Site Status ACTIVE_NOT_RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Site Status ACTIVE_NOT_RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, United States

Site Status ACTIVE_NOT_RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Site Status ACTIVE_NOT_RECRUITING

New York Proton Center

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status ACTIVE_NOT_RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Site Status ACTIVE_NOT_RECRUITING

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

Case Western Reserve University

Cleveland, Ohio, United States

Site Status RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status RECRUITING

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, United States

Site Status RECRUITING

M D Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status RECRUITING

University of Washington Medical Center - Montlake

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Site Public Contact

Role: primary

Site Public Contact

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Site Public Contact

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Site Public Contact

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Site Public Contact

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Site Public Contact

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Site Public Contact

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Site Public Contact

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Site Public Contact

Role: primary

Site Public Contact

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Site Public Contact

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Site Public Contact

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Site Public Contact

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Site Public Contact

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Site Public Contact

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Site Public Contact

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Site Public Contact

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Site Public Contact

Role: primary

References

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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.

Reference Type DERIVED
PMID: 36155490 (View on PubMed)

Other Identifiers

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NCI-2016-02009

Identifier Type: REGISTRY

Identifier Source: secondary_id

NRG-GI003

Identifier Type: OTHER

Identifier Source: secondary_id

NRG-GI003

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NRG-GI003

Identifier Type: -

Identifier Source: org_study_id