Clinical trial NCT03186898: Radiation Therapy With Protons or Photons in Treating Patients With Liver Cancer
Official title: A Phase III Randomized Trial of Protons Versus Photons for Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Recurrent Hepatocellular Carcinoma
Stage III Hepatocellular Carcinoma AJCC v7
Unresectable Hepatocellular Carcinoma
Lead sponsor: NRG Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2017-06-14
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: Overall survival (OS)
timeFrame: From the date of randomization to the date of death due to any cause assessed up to 4 years
measure: Treatment effect
timeFrame: Up to 4 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 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
measure: Local progression (LP)
timeFrame: 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
measure: Incidence of adverse events
timeFrame: Up to 4 years
measure: Fatigue
timeFrame: Baseline up to 6 months
measure: Change in fatigue
timeFrame: Baseline up to 1 month
measure: Quality-adjusted survival
timeFrame: Baseline up to 12 months
measure: Plasma hepatocyte growth factor (HGF) levels
timeFrame: At baseline
Other outcomes:
measure: Overall quality of life by Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) version 4
timeFrame: Baseline up to 12 months
Locations:
city: Atlanta
country: United States
facility: Emory Proton Therapy Center
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center Warrenville
state: Illinois
city: Baltimore
country: United States
facility: Maryland Proton Treatment Center
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Dearborn
country: United States
facility: Corewell Health Dearborn Hospital
state: Michigan
city: Royal Oak
country: United States
facility: Corewell Health William Beaumont University Hospital
state: Michigan
city: Troy
country: United States
facility: Corewell Health Beaumont Troy Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: New York Proton Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Center-UC Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: West Chester
country: United States
facility: University of Cincinnati Cancer Center-West Chester
state: Ohio
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center - Montlake
state: Washington
Study officials:
affiliation: NRG Oncology
name: Theodore S Hong
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.