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

NCT00956930 | Completed Phase 2 Results DMC

• 4 other identifiers: STU 12339P30CA060553STU# 00012339CDR0000651416
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Cancer

Keywords

advanced adult primary liver cancer; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer; adult primary hepatocellular carcinoma

Outcome Measures

Primary Outcomes (1)

• Time to Progression (TTP) in Patients Treated With TACE and Y90

  Compare and contrast TACE and Y90 in order to determine either equivalence or superiority as measured by time-to-progression. Patients have repeat imaging done (MRI or CT) at 1-month post procedure and then every 3 months after that. TTP and overall survival (OS) analyses were calculated from day of randomization by Kaplan-Meier analysis on intention-to-treat (ITT) basis. Progression (which is detected on follow-up imaging scans) was defined as: 1. Progression by World Health Organization (WHO) response criteria 25% increase in bidimensional cross product. 2. Progression by European Assosciation for the Study of the Liver (EASL): 25% increase in arterial enhancement 3. Malignant portal vein tumor thrombus development 4. Index lesion: lesions requiring re-treatment because of worsening circumferential enhancement 5. Development of new lesions or extra-hepatic metastases.

  Up to 6 yrs

Secondary Outcomes (2)

• Number of Patients Who Achieved Complete or Partial Radiologic Response After Treatment

  up to 6 years

• Overall Survival

  From day of randomization until date of death, or liver transplant or 7/15/2016, whichever came first, assessed up to 6 years

Study Arms (2)

Arm I (radioembolization)

EXPERIMENTAL

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

Radiation: yttrium Y 90 glass microspheres

Arm II (transarterial chemoembolization [TACE])

EXPERIMENTAL

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

Drug: Doxorubicin

Interventions

yttrium Y 90 glass microspheres RADIATION

Patients undergo radioembolization.

Also known as: Radioembolization

Arm I (radioembolization)

Doxorubicin DRUG

75mg fixed dose

Also known as: Doxorubicin hydrocholoride, Adriamycin, Chemoembolization (TACE)

Arm II (transarterial chemoembolization [TACE])

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[appendix C\]

You may not qualify if:

• 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).

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University, Northwestern Memorial Hospital

Chicago, Illinois, 60611-3013, United States

Location

Related Publications (1)

• 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.

  PMID: 27575820 RESULT

Related Links

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

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Doxorubicin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Limitations and Caveats

Limitations include small sample size and required censoring of imaging/survival to transplant.

Results Point of Contact

• Title: Riad Salem MD
• Organization: Northwestern University

rsalem1@nm.org

312-695-6371

Study Officials

• Riad Salem, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Vascular and Interventional Radiology

Study Record Dates

• First Submitted: August 8, 2009
• First Posted: August 11, 2009
• Study Start: August 1, 2009
• Primary Completion: June 2, 2016
• Study Completion: July 15, 2016
• Last Updated: November 21, 2022
• Results First Posted: October 1, 2019

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)