Stereotactic Body Radiation Therapy and Transarterial Chemoembolization in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

PRIMARY OBJECTIVES:

I. To establish the feasibility of completing SBRT followed by TACE in a 2 day time period.

SECONDARY OBJECTIVES:

I. To determine acute tumor perfusion changes after SBRT using functional magnetic resonance
imaging (MRI) (magnetic resonance [MR]-dynamic contrast enhanced [DCE]/perfusion weighted
imaging [PWI], MR-diffusion, blood oxygen level dependent [BOLD] sequences).

II. To establish safety and tolerability of this regimen. III. To determine overall response
rates (using modified Response Evaluation Criteria in Solid Tumors [RECIST] criteria),
including objective response rate (partial response [PR] + complete response [CR]) and
clinical benefit rate (stable disease [SD] + PR + CR) at 1, 3, and 6 months after TACE.

IV. To evaluate local control, progression-free survival, and overall survival at 1, 3, 6, 9,
and 12 months after a single-dose of SBRT followed by TACE.

V. To correlate micro ribonucleic acid (miRNA) biomarkers with response and toxicity.

OUTLINE: This is a dose-escalation study of SBRT.

Patients undergo SBRT on day 1 and TACE on day 2.

After completion of study treatment, patients are followed up at 1-2 weeks and at 1, 3, 6, 9,
12, 18, and 24 months.

Inclusion Criteria:

- Patients must have a diagnosis of hepatocellular carcinoma by at least one criterion
listed below:

- Histologically confirmed

- Magnetic resonance imaging (MRI) or computerized tomography (CT) findings
consistent with hepatocellular carcinoma

- Alpha fetoprotein (AFP) > 400 ng/mL AND evidence of at least one solid liver
lesion > 2 cm regardless of specific imaging characteristics on CT or MRI

- Patients must be non-transplantable, unresectable, or medically inoperable and
eligible for TACE as determined by a multi-disciplinary team

- Absolute neutrophil count >= 1.5 × 10^9/L

- Hemoglobin >= 9 g/dl

- Platelets >= 50,000/mm^3

- Prothrombin time (PT)/international normalized ratio (INR) and activated partial
thromboplastin time (PTTa) =< 1.5

- Albumin >= 2.5 g/dL

- Alkaline phosphatase < 5 x upper limit of normal (ULN)

- Total bilirubin =< 2.0 mg/dL

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN

- Creatinine =< 1.5 mg/dL and calculated creatinine clearance >= 60 mL/min or 24-hour
urine creatinine clearance >= 60 mL/min

- Must have Childs-Pugh A or B liver disease

- Patients must have no clinical signs of heart failure and meet New York Heart
Association functional classification I or II defined as:

- Class I - patients with no limitation of activities; they suffer no symptoms from
ordinary activities

- Class II - patients with slight, mild limitation of activity; they are
comfortable with rest or with mild exertion

- Must have 1-3 liver lesions amenable to SBRT with tumor size < 15 cm (single lesion or
sum)

- Must be able to undergo two MRI scans, one before study treatment begins and another
shortly after SBRT

- Patients with extrahepatic disease, portal hypertension, or bilobar disease are
allowed

- Normal renal function (creatinine < 1.5 mg/dL)

- Within 2 weeks of registration: patients must have vital signs, history/physical
examination, laboratory studies (complete blood count [CBC] with differential,
chemistries including liver function tests, AFP, creatinine clearance [CrCl]
assessment, pregnancy test if needed)

- Life expectancy of at least 12 weeks in the opinion of investigator

- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

- Ability to provide written informed consent obtained prior to participation in the
study and any related procedures being performed

- Women of child-bearing potential (WOCBP) must have a negative pregnancy test within 14
days of the first administration of study treatment; urine human chorionic
gonadotropin (HCG) is an acceptable pregnancy assessment

- Women/men of reproductive potential must be counseled on contraception/abstinence
while receiving the study treatment

Exclusion Criteria:

- Childs-Pugh C liver function

- Major liver vascular invasion

- Prior radiation to the liver or other upper abdominal regions

- Must not have any evidence of bleeding diathesis or active gastrointestinal bleeding

- Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder
cancer, or carcinoma in situ of the cervix; patients with a previous malignancy
without evidence of disease for >= 3 years will be allowed to enter the trial

- History of active connective tissue disease (scleroderma)

- Subjects who are breast-feeding, or have a positive pregnancy test will be excluded
from the study; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately

- Medical contraindication to MR imaging (e.g. pacemakers, metallic implants, aneurysm
clips, known contrast allergy to gadolinium contrast, pregnancy, nursing mothers,
weight greater than 350 pounds)

- Any serious and/or unstable pre-existing medical disorder (aside from malignancy
exception above), psychiatric disorder, or other conditions that could interfere with
subject's safety, obtaining informed consent or compliance to the study procedures, in
the opinion of the investigator; this could include severe, active co-morbidities such
as:

- Uncontrolled cardiac disease (hypertension, unstable angina, myocardial
infarction within last 6 months, uncontrolled congestive heart failure,
cardiomyopathy with decreased ejection fraction)

- Acute bacterial or fungal infection requiring intravenous antibiotics at time of
registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days of
registration

- Hepatic insufficiency resulting in jaundice and/or coagulation defects