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

July 31, 2023 updated by: NRG Oncology

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

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 HGF and outcomes (OS/PFS/fatigue).

EXPLORATORY OBJECTIVES:

I. To determine differences in overall Quality of Life, measured by 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.

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

Study Type

Interventional

Enrollment (Estimated)

186

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University Hospital/Winship Cancer Institute
        • Principal Investigator:
          • Pretesh R. Patel
        • Contact:
          • Site Public Contact
          • Phone Number: 404-778-1868
      • Atlanta, Georgia, United States, 30308
        • Recruiting
        • Emory University Hospital Midtown
        • Principal Investigator:
          • Pretesh R. Patel
        • Contact:
          • Site Public Contact
          • Phone Number: 888-946-7447
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Emory Saint Joseph's Hospital
        • Principal Investigator:
          • Pretesh R. Patel
        • Contact:
          • Site Public Contact
          • Phone Number: 404-851-7115
      • Atlanta, Georgia, United States, 30308
        • Recruiting
        • Emory Proton Therapy Center
        • Principal Investigator:
          • Pretesh R. Patel
        • Contact:
    • Illinois
      • Warrenville, Illinois, United States, 60555
        • Active, not recruiting
        • Northwestern Medicine Cancer Center Warrenville
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland/Greenebaum Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-888-8823
        • Principal Investigator:
          • Jason K. Molitoris
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • Maryland Proton Treatment Center
        • Contact:
        • Principal Investigator:
          • Jason K. Molitoris
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 877-726-5130
        • Principal Investigator:
          • Theodore S. Hong
    • Michigan
      • Dearborn, Michigan, United States, 48124
        • Recruiting
        • Beaumont Hospital - Dearborn
        • Principal Investigator:
          • John M. Robertson
        • Contact:
          • Site Public Contact
          • Phone Number: 248-551-7695
      • Royal Oak, Michigan, United States, 48073
        • Recruiting
        • William Beaumont Hospital-Royal Oak
        • Principal Investigator:
          • John M. Robertson
        • Contact:
          • Site Public Contact
          • Phone Number: 248-551-7695
      • Troy, Michigan, United States, 48085
        • Recruiting
        • William Beaumont Hospital - Troy
        • Principal Investigator:
          • John M. Robertson
        • Contact:
          • Site Public Contact
          • Phone Number: 248-551-7695
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Active, not recruiting
        • Washington University School of Medicine
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Active, not recruiting
        • Memorial Sloan Kettering Basking Ridge
      • Middletown, New Jersey, United States, 07748
        • Active, not recruiting
        • Memorial Sloan Kettering Monmouth
      • Montvale, New Jersey, United States, 07645
        • Active, not recruiting
        • Memorial Sloan Kettering Bergen
    • New York
      • Commack, New York, United States, 11725
        • Active, not recruiting
        • Memorial Sloan Kettering Commack
      • Harrison, New York, United States, 10604
        • Active, not recruiting
        • Memorial Sloan Kettering Westchester
      • New York, New York, United States, 10065
        • Active, not recruiting
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10035
        • Suspended
        • New York Proton Center
      • Uniondale, New York, United States, 11553
        • Active, not recruiting
        • Memorial Sloan Kettering Nassau
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • University of Cincinnati Cancer Center-UC Medical Center
        • Principal Investigator:
          • Jordan Kharofa
        • Contact:
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • Case Western Reserve University
        • Principal Investigator:
          • Lauren E. Henke
        • Contact:
      • West Chester, Ohio, United States, 45069
        • Recruiting
        • University of Cincinnati Cancer Center-West Chester
        • Principal Investigator:
          • Jordan Kharofa
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • M D Anderson Cancer Center
        • Principal Investigator:
          • Eugene J. Koay
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • FHCC South Lake Union
        • Principal Investigator:
          • Smith Apisarnthanarax
        • Contact:
          • Site Public Contact
          • Phone Number: 800-804-8824
      • Seattle, Washington, United States, 98195
        • Recruiting
        • University of Washington Medical Center - Montlake
        • Principal Investigator:
          • Smith Apisarnthanarax
        • Contact:
          • Site Public Contact
          • Phone Number: 800-804-8824

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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
    • Patients 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 legion that is ≥ 1 cm and ≤ 15 cm in greatest dimension is allowed.
  • 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 >= 2.5mg/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 RANDOMIZATION:
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Proton Therapy (Radiation Therapy)
Patients undergo proton therapy over 15-24 days for 5 or 15 fractions.
Radiation: Proton Therapy (Radiation Therapy)
Undergo proton therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
  • Radiation Therapy
  • RADIATION
Experimental: Photon Therapy (Radiation Therapy)
Patients undergo photon therapy over 15-24 days for 5 or 15 fractions.
Radiation: Photon Therapy (Radiation Therapy)
Undergo photon therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
  • Radiation Therapy
  • RADIATION

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From the date of randomization to the date of death due to any cause or date of last follow-up for alive patients. This analysis occurs after 125 deaths have been observered; estimated to occurs around 5 years.
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 Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, that may be associated with OS.
From the date of randomization to the date of death due to any cause or date of last follow-up for alive patients. This analysis occurs after 125 deaths have been observered; estimated to occurs around 5 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: 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 5 years.
PFS is defined as local/regional/distant progression or death due to any cause and will be estimated by the Kaplan-Meier method. The distributions of PFS between treatment arms will be compared using the log rank test.
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 5 years.
Local Progression (LP)
Time Frame: 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 5 years.
LP will be estimated by the cumulative incidence method and compared using Gray's test. The Fine-Gray regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with 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 5 years.
Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 5
Time Frame: From baseline up to 5 years
A Chi-square test will be used to compare the number of patients with at least 1 grade 3 or higher adverse events between the treatment arms.
From baseline up to 5 years
Fatigue as measured by the PROMIS fatigue short form version 1.0 8a
Time Frame: From baseline to the assessment at 1 month post treatment completion.
Change in fatigue will be compared between treatment arms using a t-test. If the data do not satisfy the normality assumption, a Wilcoxin test may be used instead.
From baseline to the assessment at 1 month post treatment completion.
Correlation of Hepatocyte Growth Factor (HGF) biomarker with OS, PFS and fatigue
Time Frame: This analysis occurs after the primary endpoint has been reported; estimated to occur around 5 years.
HGF will be dichotomized at 2311 pg/mL and evaluated for prognostic significance using Cox regression model.
This analysis occurs after the primary endpoint has been reported; estimated to occur around 5 years.
Quality Adjusted Survival (if primary endpoint is met)
Time Frame: This analysis occurs after the primary endpoint has been reported; estimated to occur around 5 years.
The EuroQol (EQ-5D) will be used to assess quality-adjusted survival.
This analysis occurs after the primary endpoint has been reported; estimated to occur around 5 years.
Exploratory - Overall Quality of Life (QOL)
Time Frame: From baseline to the assessment at 6 months post treatment completion
QOL will be measured by the FACT-Hep v 4. An improvement in the FACT-HEP, defined as an increase of 5 points, will be assessed.
From baseline to the assessment at 6 months post treatment completion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NRG Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Theodore Hong, NRG Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 22, 2017

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

June 30, 2029

Study Registration Dates

First Submitted

June 12, 2017

First Submitted That Met QC Criteria

June 12, 2017

First Posted (Actual)

June 14, 2017

Study Record Updates

Last Update Posted (Actual)

August 2, 2023

Last Update Submitted That Met QC Criteria

July 31, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NRG-GI003 (Other Identifier: CTEP)
  • U10CA180868 (U.S. NIH Grant/Contract)
  • NCI-2016-02009 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Unrectable or Locally Recurrent Hepatocellular Carcinoma

Clinical Trials on Proton Therapy (Radiation Therapy)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Dominican Republic

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe