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

NCT ID: NCT00956930

Last Updated: 2022-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2016-07-15

Brief Summary

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.

Detailed 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.

Conditions

Liver Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (radioembolization)

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

Group Type: EXPERIMENTAL

yttrium Y 90 glass microspheres

Intervention Type: RADIATION

Patients undergo radioembolization.

Arm II (transarterial chemoembolization [TACE])

Patients undergo TACE with mitomycin C, doxorubicin hydrochloride, and cisplatin by hepatic artery infusion for approximately 1-3 courses.

Group Type: EXPERIMENTAL

Doxorubicin

Intervention Type: DRUG

75mg fixed dose

Interventions

yttrium Y 90 glass microspheres

Patients undergo radioembolization.

Intervention Type: RADIATION

Doxorubicin

75mg fixed dose

Intervention Type: DRUG

Other Intervention Names

Radioembolization; Doxorubicin hydrocholoride; Adriamycin; Chemoembolization (TACE)

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Riad Salem

Chief Vascular and Interventional Radiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Riad Salem, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern University, Northwestern Memorial Hospital

Chicago, Illinois, United States

Countries

United States

References

Salem R, Gordon AC, Mouli S, Hickey R, Kallini J, Gabr A, Mulcahy MF, Baker T, Abecassis M, Miller FH, Yaghmai V, Sato K, Desai K, Thornburg B, Benson AB, Rademaker A, Ganger D, Kulik L, Lewandowski RJ. Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma. Gastroenterology. 2016 Dec;151(6):1155-1163.e2. doi: 10.1053/j.gastro.2016.08.029. Epub 2016 Aug 27.

Reference Type: RESULT

PMID: 27575820 (View on PubMed)

Related Links

https://www.ncbi.nlm.nih.gov/pubmed/27575820

Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma

Other Identifiers

P30CA060553

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU# 00012339

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000651416

Identifier Type: OTHER

Identifier Source: secondary_id

STU 12339

Identifier Type: -

Identifier Source: org_study_id