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

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.

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