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

Northwestern University

Status and phase

Completed

Phase 2

Conditions

Liver Cancer

Treatments

Drug: Doxorubicin

Radiation: yttrium Y 90 glass microspheres

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00956930

CDR0000651416 (Other Identifier)

P30CA060553 (U.S. NIH Grant/Contract)

STU 12339

STU# 00012339 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. Radioembolization kills tumor cells by blocking the blood flow to the tumor and keeping radioactive substances near the tumor. It is not yet known which treatment regimen is more effective in treating patients with liver cancer.

PURPOSE: This randomized phase II trial is studying radioembolization to see how well it works compared with chemoembolization in treating patients with liver cancer that cannot be treated with Radiofrequency Ablation or removed by surgery.

Full description

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.

Enrollment

45 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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).