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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Northwestern University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Riad Salem, Northwestern University
ClinicalTrials.gov Identifier:
NCT00956930
First received: August 8, 2009
Last updated: May 13, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Liver Cancer
Radiation: yttrium Y 90 glass microspheres
Drug: Doxorubicin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Investigator Initiated Multicenter Prospective Randomized Study of Chemoembolization Versus Radioembolization for the Treatment of Hepatocellular Carcinoma (PREMIERE Trial)

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Time to progression in patients treated with TACE and Y90 [ Time Frame: up to 6 yrs ] [ Designated as safety issue: No ]
    Compare and contrast TACE and Y90 in order to determine either equivalence or superiority as measured by time-to-progression. They have repeat imaging done (MRI or CT) 1 month post procedure and then every 3 months after that.


Secondary Outcome Measures:
  • Characterize the safety and toxicity profile of these regimens [ Time Frame: up to 6 years ] [ Designated as safety issue: Yes ]
    After treatment toxicities are evaluated in patients at 2 weeks, 4 weeks, and then every 3 months post-treatment.

  • Determine tumor response and the need for subsequent treatment in these patients [ Time Frame: up to 6 years ] [ Designated as safety issue: No ]
    Repeat imaging (CT/MRI) and lab work including tumor markers will be assessed 1 month post-treatment then every 3 months after that.

  • Characterize change in quality of life and performance status in these patients [ Time Frame: up to 6 years ] [ Designated as safety issue: Yes ]
    Subjects complete a Fact-Hep quality of life questionnaire pre-treatment, 1 month post-treatment and then every three months post-treatment. Performance status is evaluated pre-treatment, 1 month and then every 3 months post-treatment.


Estimated Enrollment: 124
Study Start Date: August 2009
Estimated Study Completion Date: August 2020
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (radioembolization)
Patients undergo radioembolization with yttrium Y 90 glass microspheres by hepatic artery infusion for approximately 1-3 courses.
Radiation: yttrium Y 90 glass microspheres
Patients undergo radioembolization.
Other Name: Radioembolization
Experimental: Arm II (transarterial chemoembolization [TACE])
Patients undergo TACE with mitomycin C, doxorubicin hydrochloride, and cisplatin by hepatic artery infusion for approximately 1-3 courses.
Drug: Doxorubicin
75mg fixed dose
Other Names:
  • Doxorubicin hydrocholoride
  • Adriamycin
  • Chemoembolization (TACE)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  • 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00956930

Contacts
Contact: Riad Salem, MD, MBA 312-695-6371 r-salem@northwestern.edu
Contact: Carlene del Castillo, RN BSN 312-695-9882 carlene.castillo@northwestern.edu

Locations
United States, Illinois
Northwestern University, Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611-3013
Contact: Carlene del Castillo, RN BSN    312-695-9882    carlene.castillo@northwestern.edu   
Contact: Jennifer Karp, RN BSN    312-926-5289    jkarp@nm.org   
Sub-Investigator: Laura Kulik, MD         
Sub-Investigator: Robert Lewandowski, MD         
Sub-Investigator: Kent Sato, MD         
Sub-Investigator: Albert Nemcek, MD         
Sub-Investigator: Mary Mulcahy, MD         
Sub-Investigator: Al Benson, MD         
Sub-Investigator: Michael Abecassis, MD         
Sub-Investigator: John Fryer, MD         
Sub-Investigator: Talia Baker, MD         
Sub-Investigator: Ahsun Riaz, MD         
Sub-Investigator: Vanessa Gates, MS, DABR, DABSNM         
Sub-Investigator: Kush Desai, MD         
Sub-Investigator: Ryan Hickey, MD         
Sub-Investigator: Halla Nimeiri, MD         
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Riad Salem, MD Northwestern University
  More Information

Additional Information:
No publications provided

Responsible Party: Riad Salem, Chief Vascular and Interventional Radiology, Northwestern University
ClinicalTrials.gov Identifier: NCT00956930     History of Changes
Other Study ID Numbers: STU 12339, P30CA060553, STU# 00012339, CDR0000651416
Study First Received: August 8, 2009
Last Updated: May 13, 2015
Health Authority: United States: Food and Drug Administration
United States: Northwestern University IRB

Keywords provided by Northwestern University:
advanced adult primary liver cancer
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer
adult primary hepatocellular carcinoma

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Adenocarcinoma
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on June 29, 2015