RAD 0902: A Pilot Study of Trans Arterial Chemoembolization (TACE), Followed by Stereotactic Radiation Therapy (SBRT) for Patients With Hepatocellular Carcinoma

Inclusion Criteria:

Diagnosis

Patients meeting all the following criteria will be considered for enrollment:

- Pathologically confirmed HCC -OR

- HCC greater than 2 cm with classic radiographic findings on 2 separate testing
modalities, or an HCC greater than 2 cm with a serum alpha feto-protein greater than
200.

Lesions:

Single liver lesion: measuring 3 cm to ≤ 8 cm*.

- Multiple liver lesions: ≤ 3 liver lesions, none measuring over 5 cm, provided all
lesions are considered for TACE.

- Lesions <3 cm if they are in an unfavorable location for ablation† *The size criteria
of hepatic lesions are also subjected to the dose volume constraints for
radiotherapy, as described below.

Patient

- Patient deemed to not be a liver transplant candidate (or refuse transplant).

- Patient deemed to not be a candidate for surgical resection (or refuse surgical
resection).

- Patient deemed to not be a candidate for ablation (or refuse ablation therapy).

- Patient must be a candidate and receive TACE.

- ECOG Zubrod Performance Scale = 0-1.

- Age > 19

- Patient should not be pregnant. Women of childbearing potential and male
participants must practice adequate contraception.

Adequate organ function as evidence by:

Hematology

- Absolute neutrophil count (ANC) > 1,200 cells/mm3 < 2 weeks prior to entry

- Platelets > 40,000 cells/mm3 < 2 weeks prior to entry into study

- Hemoglobin > 8 g/dl < 2 weeks prior to entry into study

Liver Functions

- s.Bilirubin should be < 2 times the normal limit, INR should be <2, and liver enzymes
less than 3 times the normal limits drawn within 2 weeks prior to study entry.

- Patients who have developed a tumor recurrence following a liver transplant, liver
resection or liver ablation are eligible for this study.

- Patients with Child Pugh Class A & B disease are eligible for the study; Class C
patients are ineligible. Patients with normal liver function or compensated cirrhosis
are eligible for the study. However, patients with poorly controlled ascites are
ineligible for the study (see below).

- Patients with clinically significant liver failure are ineligible.

- Underlying liver cirrhosis is not a contraindication for entry, but should be
recorded for analysis of relationship to toxicity development.

Signed informed consent document

Male or female patients of any ethnic group. Female patients must be surgically sterile,
postmenopausal (no menses for at least one year), or using medically approved method of
contraception (excluding rhythm, withdraw or abstinence). Men must agree to use a
medically approved method of contraception (excluding rhythm, withdraw or abstinence).

Age > 19 years.

Complete initial work-up within 4 weeks prior to randomization for imaging and within 7
days prior to randomization for clinical evaluation and biological work-up.

Exclusion Criteria:

Patients presenting with any of the following will not be included in the study:

1. Prior invasive malignancies are ineligible. For example a patient cannot be
registered for this study for treatment of HCC, if there is a history of prior
colorectal cancer. (Patients with non-melanoma skin cancer or in situ cancers of the
breast, oral cavity, or cervix are eligible).

2. Prior radiotherapy to the liver or surrounding areas that would result in overlap of
radiation therapy fields is an ineligibility criterion. Patients with other known
contraindications to radiation including systemic sclerosis, ulcerative colitis etc.
also are ineligible.

3. Systemic therapy using any chemotherapy and/or targeted agents given within 2 weeks
prior to TACE, during RT, and / or within 3 weeks following RT completion are grounds
for exclusion. Patients who received Bevacizumab or other vascular endothelial
growth factor antagonists 2 months prior or following TACE/ RT are ineligible.
Administration of Anthracyclines or other chemotherapy agents with dominant
hepatotoxicity within 8 weeks of completion of RT is also an exclusion criterion.

4. Severe co-morbidity including (but not restricted to) unstable angina and/or
congestive heart failure requiring hospitalization within the last 6 months,
transmural myocardial infarction within the last 6 months, uncontrolled arterial
hypertension, uncontrolled diabetes mellitus, dementia, acute infections (bacterial,
fungal or HIV infection requiring oral or intravenous antibiotics at the time of
registration, severe chronic airway disease (COPD) other serious illness requiring
hospitalization or precluding study therapy at the time of registration are
contraindications.

5. Patients who are receiving anticoagulation treatment with coumadin or IV heparin
(including anticoagulation to maintain central line) resulting in INR > 2 times
normal are ineligible.

6. Uncontrolled or symptomatic clinical ascites makes patient ineligible for the study

7. Major surgical procedure within 3 weeks prior to study entry.

8. History of hypersensitivity to chemotherapy agents, contrast material.

9. Pregnancy, breast-feeding or planning to become pregnant.

10. Treatment with any investigational product in the last 4 weeks before study entry.

11. Mental condition rendering the subject unable to understand the nature, scope, and
possible consequences of the study.

Patients of Reproductive Potential

The patient must not be pregnant or breast-feeding at enrollment in the study. Absence of
pregnancy must be demonstrated by serum or urine testing prior to exposure enrollment into
the study.

Female patients of child bearing potential (i.e., ovulating, premenopausal, not surgical
sterile) must use a medically accepted contraceptive regimen. Male patients must agree to
use a medically approved method of contraception.