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.
• Patients 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).