TATE Versus TACE in Intermediate Stage HCC

Trans-arterial chemoembolization (TACE) is a standard care of intermediate stage
Hepatocellular carcinoma (HCC) for 40 years without much improvement in efficacy. The key
reason for lack of progress is that chemotherapy agents are not effective in hypoxia and
cancer stem cells are induced under hypoxia. Tirapazamine, a hypoxia activated agent, can
potential solve these two problems. This open label randomized trial will be conducted in HCC
patients who are in intermediate stage and naive to embolization, Child Pugh up to B7 and
with normal organ functions. Patients will be randomized 1:1 to receive TATE (trans-arterial
tirapazamine embolization) or conventional TACE. The goal of treatment aims to achieve CR by
mRECIST for every patient. If there is evidence of viable lesion, patients should be treated
again. All patients are followed by contrast MRI scans every 2 months in the first year and
every 3 months afterwards until patients have evidence of progression and no longer
considered suitable for TATE/TACE. Survival will be followed for 3 years. Total sample size
will be 134 patients with the total study duration for 3 years.

1. Confirmed diagnosis of HCC by imaging criteria per American Association for the Study
of Liver Diseases (AASLD) criteria.

2. Patients with single or multiple HCC who are unsuitable for surgical resection or RFA,
but suitable for embolization.

3. ECOG score 0-1. Child-Pugh score up to B7.

4. Patients should have measurable tumor lesion(s) by contrast MRI.

5. Patients have adequate normal organ function and suitable laboratory criteria.

6. Men and women of child-bearing age need to commit to using two levels of contraception
simultaneously to avoid pregnancy.

Exclusion Criteria:

1. Patients who have had a liver transplantation.

2. Patients who have uncontrolled major medical problems such as cardiac, pulmonary (COPD
requiring constant oxygen), renal (creatinine over 2.0) diseases, active infectious
diseases (except chronic Hepatitis B or C), or non-healing ulceration.

3. Patients who have any clinical evidence of hypoxia with O2 saturation less than 92% on
room air.

4. Patients with evidence of arterial insufficiency or microangiopathy in any organ due
to any reason, which could lead to distal extremity hypoxia, as evidenced by any
gangrenous change in distal limbs or requiring resection for this reason.

5. Patients with poorly controlled HBV infection.

6. Patients on interferon treatment need to have at least 2-week washout period from Day
1.

7. Patients with major gastrointestinal bleeding in the prior 2 months of enrollment or
known diagnosis of cancer other than HCC.

8. Pregnant or lactating women.