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

This study is currently recruiting participants.
Verified June 2017 by NRG Oncology
Sponsor:
ClinicalTrials.gov Identifier:
NCT03186898
First Posted: June 14, 2017
Last Update Posted: June 26, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology
  Purpose
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.

Condition Intervention
Unrectable or Locally Recurrent Hepatocellular Carcinoma Radiation: Proton Therapy (Radiation Therapy) Radiation: Photon Therapy (Radiation Therapy)

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial of Protons Versus Photons for Hepatocellular Carcinoma

Further study details as provided by NRG Oncology:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.

  • 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.

  • Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4 [ 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.

  • 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.

  • 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.

  • 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.

  • 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.


Estimated Enrollment: 186
Actual Study Start Date: June 22, 2017
Estimated Study Completion Date: August 31, 2027
Estimated Primary Completion Date: August 1, 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • RADIATION
  • Radiation Therapy
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • 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
  • RADIATION
  • Radiation Therapy
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
    • 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 ≥ 4 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03186898


Locations
United States, Pennsylvania
NRG Oncology Recruiting
Philadelphia, Pennsylvania, United States, 19103
Contact: Theodore S. Hong, MD    617-726-6050    tshong1@mgh.harvard.edu   
Principal Investigator: Theodore S. Hong, MD         
Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Investigators
Principal Investigator: Theodore Hong NRG Oncology
  More Information

Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT03186898     History of Changes
Other Study ID Numbers: NRG-GI003
NCI-2016-02009 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GI003 ( Other Identifier: NRG Oncology )
NRG-GI003 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Submitted: June 12, 2017
First Posted: June 14, 2017
Last Update Posted: June 26, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by NRG Oncology:
hepatocellular carcinoma
HCC
Proton Therapy
Photon Therapy
Liver cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases