TACE With or Without Radiation Therapy in Treating Patients With Stage A-C Liver Cancer

PRIMARY OBJECTIVES:

I. To determine in patients with stage A to C hepatocellular carcinoma, if stereotactic body
radiotherapy after TACE enhanced the response rate of hepatocellular carcinoma (HCC) when
compared to TACE alone at 3 months.

SECONDARY OBJECTIVES:

I. To determine in patients with stage A to C hepatocellular carcinoma, if TACE plus SBRT
can achieve a downstaging rate of >= 30% at 3 and 6 months.

II. To determine the rate of grade 3 or 4 adverse events associated with SBRT for liver
tumors.

III. To determine the rate of local progression after SBRT. (Based on Response Evaluation
Criteria in Solid Tumors [RECIST] criteria) IV. Number of patients who achieve liver
transplantation. V. Overall survival.

OUTLINE: Patients are randomized to 1 of 2 treatment arms after the first loco-regional
therapy with TACE.

ARM I: Patients undergo TACE according to institutional standard with doxorubicin-eluting
beads.

ARM II: Patients undergo TACE as in Arm I and 3 or 5 fractions of SBRT given at least 48
hours apart over 14 days.

After completion of study treatment, patients are followed up at 1, 3, and 6 months and then
periodically thereafter.

Inclusion Criteria:

- HCC is staged as Barcelona A to C

- Treatment with SBRT can occur within 6 weeks of registration

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Patient has

- Radiographic enhancing liver lesions with early wash out on triple phase CT or
MRI or

- Histological confirmation of HCC as determined by the Liver Tumor Board

- Hemoglobin greater than 10.0 g/dL

- Total bilirubin less than 3.0 mg/dL

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =<
3 X institutional upper limit of normal

- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X
institutional upper limit of normal

- Total aggregate of maximal dimension of liver tumors is =< 8 cm

- Cirrhotic patients Child Pugh class A or B (score =< 7)

- Patient must be determined by the treating physician to be medically eligible for
liver transplantation measured by imaging modality (magnetic resonance imaging
[MRI]/computed tomography [CT] scan) three months post final treatment

- Absolute neutrophil count >= 1,500/μl

- Platelet count >= 50,000 μl (after transfusion if required)

- Life expectancy > 12 weeks

- Subjects must have the ability to understand and be willing to provide written
informed consent

- Women of child-bearing potential must have a negative pregnancy test within 4 weeks
to the start of the SBRT treatment

- Women must not be pregnant or nursing

- Sexually active women must agree to use accepted forms of birth control; acceptable
options for birth control will be documented in the consent and discussed with the
subject prior to enrollment

Exclusion Criteria:

- Patient with previous history of abdominal radiation

- Cirrhotic patients Child Pugh class B with score >= 8

- Prior invasive malignancy other than primary liver malignancy (except
non-melanomatous skin cancer) unless disease free for a minimum of 3 years

- Evidence of metastatic disease prior to registration

- Evidence of main portal vein thrombosis

- History of known cardiac ischemia or stroke within last 6 months

- Any concurrent medical or psychosocial condition that prohibits a major surgical
procedure or immunosuppression that would constitute a contraindication to liver
transplantation