Chemoembolization Versus Radioembolization in Treating Patients With Liver Cancer That Cannot Be Treated With Radiofrequency Ablation Or Surgery

OBJECTIVES:

Primary

- Compare and contrast TACE and Y90 in order to determine either equivalence or
superiority as measured by time-to-progression.

Secondary

- Characterize the safety and toxicity profile of these regimens.

- Determine the need for subsequent treatment in these patients.

- Determine tumor response in these patients

- Characterize change in quality of life and functional status in these patients.

- Determine time to progression in these patients.

OUTLINE: Patients are randomized to receive either TACE or Y90

- Arm I (radioembolization): Patients undergo radioembolization with yttrium Y 90 glass
microspheres by hepatic artery infusion for approximately 1-3 courses.

- Arm II (transarterial chemoembolization [TACE]): Patients undergo TACE with mitomycin
C, doxorubicin hydrochloride, and cisplatin by hepatic artery infusion for
approximately 1-3 courses.

- In both arms, treatment modifications may apply according to response.

After completion of study treatment, patients are followed every 3 months.

DISEASE CHARACTERISTICS:

- Hepatocellular Carcinoma confined to the liver that is unresectable with surgery or
unable to be treated with radiofrequency ablation diagnosed by biopsy or imaging
criteria (CT/MRI)

- No segmental, lobar, or main portal vein thrombosis as evidenced by CT or MRI imaging

Inclusion Criteria

- Adults > 18 years old of either gender

- Diagnosis of liver confined HCC confirmed by histology or American Association for
the Study of Liver Diseases (AASLD) guidelines [59,60] [appendix A].

- Lesions < 1 cm in diameter have a low likelihood of being malignant and should be
followed. Lack of growth over 1-2 years suggests it is not HCC.

- AFP >200 and radiological evidence (arterial hypervascularity) of lesion > 2 cm does
not require biopsy.

- Two imaging modalities (triphasic CT, MRI, ultrasound, angiography) demonstrating
"arterial hypervascularity" in the background of cirrhosis does not require biopsy

- One imaging modality with a lesion with arterial hypervascularity with wash out in
early or delayed venous phase, does not require a biopsy

- Atypical appearances on imaging requires a biopsy.

- Non-conclusive biopsy requires closer monitoring

- For non-cirrhotics (by biopsy or imaging findings), diagnosis of HCC requires biopsy

- Patients with <50% liver involvement

- Measurable liver confined disease with bi-dimensional measurements, required within 4
weeks of screening. Lesions reported on imaging as "too small to characterize",
abdominal lymph nodes < 2.0 cm or ascites in the setting of cirrhosis are not
considered metastatic disease unless cytology proven.

- No segmental, lobar or main portal vein thrombosis as evidence by cross sectional
imaging

- Prior resection permitted, no prior systemic, ablative or infusion therapy permitted

- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 [appendix B]

- Childs score of A or B [appendix C]

- Required lab parameters within 28 days of screening

- Serum bilirubin ≤ 2.0 mg/dl (unless segmental infusion can be performed

- AST and ALT ≤ 5 times upper limit of normal (ULN)

- Creatinine ≤ 1.5 times ULN

- Prothrombin time (PT)/ International normalized ratio (INR) ≤ 2.3 or PT ≤ 6 seconds
above control. If subjects are being anticoagulated they can participate if proof of
no coagulation abnormality existed prior to use of anticoagulants

- Negative serum or urine pregnancy test for females of child bearing potential

- Ability to understand and sign the informed consent; patient must have signed
informed consent prior to registration on study

- Women of childbearing potential and sexually active males must use contraception
while on study

- Lesions must be treatable angiographically by either radioembolization or
chemoembolization.

Exclusion criteria

- Cardiac disease: Congestive heart failure > class II New York Heart Association
(NYHA). Patients must not have unstable angina (angina symptoms at rest) or new onset
angina (began within the last 3 months) or myocardial infarction within the past 6
months.

- Patients with infiltrative HCC are not eligible.

- Patients with bulk disease (≥70% tumor replacement of liver) are not eligible.

- Pateints with ≥50% tumor replacement of liver, with an albumin < 3.0 g/dl are not
eligible.

- Major surgery within 4 weeks prior to the screening visit

- Active clinically serious infection > Common Toxicity Criteria for Adverse Events
(CTCAE v 4.0) Grade 2

- Any condition (psychological, physical or use/abuse of substances) which, in the
opinion of the principal investigator (PI) or a sub-investigator (sub-I), would
possibly endanger the subject during their participation in the study, or allow for
non-compliance with the investigational drug and treatment under study.

- Due to the experimental nature of the therapy and the unknown risk to a fetus,
pregnant and/or lactating women are not eligible to participate in this study.

- In the opinion of the investigator, patient is not a candidate/lesion not amenable
for RFA (e.g. lesion location, shape, abnormal coagulation parameters,
multi-focality).