A Pilot Study of "OncozeneTM" Microspheres for Intra-arterial Delivery of Doxorubicin

The study will evaluate the safety and tolerability of doxorubicin loaded ONCOZENE
microspheres chemoemobilization for the treatment of unresectable hepatocellular carcinoma.

The study will also describe the overall response rates of lesions with
Oncozene-DEB-TACE(Trans-arterial chemoemobilization) per modified RECIST criteria (Response
Evaluation Criteria in Solid Tumors).

Determine progression free survival (PFS) and overall survival (OS) following
Oncozene-DEB-TACE (Trans-arterial chemoemobilization)

Inclusion Criteria:

- Patients must have a diagnosis of Hepatocellular carcinoma confirmed by at least one
of the following: a) histological confirmation; b) imaging results consistent with
cirrhosis and at least one solid liver lesion of >2cm with early enhancement and
delayed washout (AASLD criteria for diagnosis of HCC); c) Alpha fetoprotein level
>400ng/mL and evidence of at least one solid liver lesion >2cm, regardless of specific
imaging characteristics on MRI.

- Tumor not suitable for resection at the time of study entry. (Transplant eligible
patients are allowed)

- Age ≥ 18 years.

- Performance status ECOG PS 0-1 (Eastern Cooperative Oncology Group Performance
Status).

- Child Pugh Score A only

- Adequate organ and marrow function as defined below:

- leukocytes ≥ 3,000/mcL (Measurement and Calibration Lab)

- absolute neutrophil count ≥ 1,500/mcL

- platelets ≥ 75,000/mcl

- total bilirubin ≤ 3.0

- AST (Aspartate Aminotransferase)(SGOT)/ALT (Alanine Aminotransferase)(SPGT) ≤ 5 X
institutional upper limit of normal

- creatinine ≤ 2.0

- INR (International Normalized Ratio) ≤ 1.8

- Albumin ≥ 2.8

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 90 days following completion of therapy.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately.

- A female of child-bearing potential is any woman (regardless of sexual orientation,
having undergone a tubal ligation, or remaining celibate by choice) who meets the
following criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy

- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has
had menses at any time in the preceding 12 consecutive months).

- Absence of occlusive thrombus in the main portal vein

- Life expectancy of at least 6 months

- Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

- Chemotherapy or radiotherapy within 4 weeks prior to entering the study or those with
residual treatment related toxicity of greater than grade 1 not addressed in inclusion
criteria.

- Any concurrent therapy for HCC including concurrent investigational agents.

- Subjects with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to doxorubicin or other agents used in study.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Subjects must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.

- Child-Pugh status B or C

- Encephalopathy no adequately controlled medically

- Known cardiac ejection fraction <50%

- Tumor involving >50% of the liver

- Infiltrative form of HCC on imaging; If there is at least one measurable lesion per
mRECIST criteria and otherwise patient is eligible for the study, the patient can be
enrolled.

- Extensive extrahepatic spread of hepatocellular carcinoma. Patients with limited
metastatic disease may be enrolled as defined as

- lymph node disease

- pulmonary nodules <5 mm in size

- 1-3 bone metastases

- Active gastrointestinal bleeding

- Evidence of uncontrollable bleeding diathesis

- Any contra-indication to angiography

- Any known contra-indication to chemoembolization according to the treating physician