Effect of Surefire Infusion Device on Tumor Response to Regional Intra-arterial Therapy for Primary Liver Malignancies

This research study is a randomized Pilot study, which is the first time investigators are
examining use of the Surefire device to improve tumor perfusion. Specifically, this study
compares TACE both with or without the use of the Surefire device

Investigators are doing this research to determine if a Surefire Infusion System can improve
tumor response to liver-directed intra-arterial chemotherapy compared to a traditional
microcatheter.

Surefire is a Food and Drug Administration-approved valve-like device that blocks backflow
within the artery but also generates increased pressure in a tumor feeder vessel during
infusion. During this study, participants will receive the same medication in the same dose
and the same way it would be delivered to the liver as a standard of care procedure, only
either through a regular microcatheter (which is the standard of care procedure) or a
Surefire Infusion System (which is a modified microcatheter).

Inclusion Criteria:

- Unresectable HCC, defined by imaging criteria or cytohistologic assessment. TACE as a
preferred method of treatment is determined by a multidisciplinary Brigham and Women's
Hospital / Dana Farber Cancer Institute (BWH/DFCI) Liver Tumor Board.

- Intermediate stage HCC (BCLC class B), not eligible for curative treatment, but with
Child-Pugh A or B. Additionally, tumor cannot involve greater than 50% of the entire
liver.

- Prior systemic chemotherapy is allowable.

- Age 18-75 years. The pediatrics population is not included as this disease has very
low prevalence in that population.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%, see
Appendix A)

- Life expectancy of greater than at least 12 months.

- Participants must have normal organ and marrow function as defined below:

- leukocytes ≥3,000/mcL

- absolute neutrophil count ≥1,500/mcL

- platelets ≥60,000/mcL

- total bilirubin within normal institutional limits

- Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) ≤2.5 ×
institutional upper limit of normal

- creatinine within normal institutional limits or,

- creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels
above institutional normal.

- No previous regional treatment (includes surgery, radiation or liver-directed arterial
or ablative therapy).

- Main tumor size > 1 cm

- The effects of the study arm on the developing human fetus are unknown, however they
are no different than for those in the control group. In addition, because significant
radiation will be delivered during the procedure, a positive pregnancy test will
exclude patients from the study in addition to excluding them from receiving standard
therapy.

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

Exclusion Criteria:

- Participants who have had prior local regional therapy including radiation therapy,
trans-arterial therapy, or ablative therapy.

- A hypovascular tumor (defined as a tumor with all its parts less contrast-enhanced
than the non-tumorous liver parenchyma on arterial phase computed tomography scans).

- Participants 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.

- Evidence of hepatic decompensation including esophageal or gastric variceal bleeding
or hepatic encephalopathy.

- Severe underlying cardiac or renal diseases.

- Color Doppler ultrasonography showing portal vein tumor thrombosis with complete main
portal vein obstruction without cavernous transformation; or obstructive jaundice.

- 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.

- Human Immunodeficiency Virus (HIV)-positive patients are NOT excluded from the study.

- Patients who cannot undergo MRI evaluation/examination (eg. pacemaker or other
metallic implant)

- History of allergic reactions attributed to agents used in study (i.e. doxorubicin,
epirubicin, MRI contrast agents or iodinated contrast agents).

- Pregnant women are excluded from this study because the chemotherapy utilized within
the chemoembolic agent is teratogenic agent with the potential for teratogenic or
abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with chemoembolic
agent, breastfeeding should be discontinued if the mother is treated with chemoembolic
agent. These potential risks may also apply to other agents used in this study as well
as from the radiation associated with the angiographic procedure.