Chemoembolization With or Without Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery
Hepatocellular Carcinoma, Unresectable Hepatocellular Carcinoma
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Unresectable Hepatocellular Carcinoma, chemoembolization, double-blind
Eligibility Criteria
Inclusion Criteria:
Patients must have a diagnosis of hepatocellular carcinoma by at least one criterion listed below:
- Histologically confirmed
- Magnetic resonance imaging (MRI) or computerized tomography (CT) consistent with liver cirrhosis AND at least one solid liver lesion > 2 cm with early enhancement and delayed enhancement washout regardless of alpha-feto protein levels (AFP)
- AFP > 400 ng/mL AND evidence of at least one solid liver lesion > 2 cm regardless of specific imaging characteristics on CT or MRI
- Patients must have hepatocellular carcinoma (HCC) limited to the liver; there must be no clinical or radiographic evidence of extrahepatic HCC
- Portal lymphadenopathy IS permitted for patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) - as lymphadenopathy is commonly associated with hepatitis unrelated to malignancy
- Staging CT of the chest and CT or MRI of the abdomen and pelvis must have been completed within 4 weeks of study registration
- Patients must have measurable disease constituting < 50% of liver parenchyma within 4 weeks of registration
- Patients may not have ascites detectable on physical examination
- Patients must not be candidates for curative resection, orthotopic liver transplantation, or radiofrequency ablation (RFA)
- Patients may have been treated with RFA in the past, but no sooner than 4 weeks before study registration
- Patients may have undergone previously attempted curative liver resection
- Patients may NOT have been previously treated with brachytherapy such as yttrium-90 microsphere
- Patients may NOT have been previously treated with sorafenib, chemoembolization, or systemic chemotherapy including cytotoxic agents or molecularly targeted agents
- Branch portal vein invasion by tumor is permitted but patients with main portal vein invasion by tumor are not eligible
- Patients must have Child-Pugh score of A or B7 within 4 weeks prior to study registration
- Serum total bilirubin =< 2.0 mg/dL
- Alkaline phosphatase < 5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 5 x ULN
- Serum creatinine =< 1.5 mg/dL
- Platelet count >= 50,000/mm^3
- Patients must not have any evidence of bleeding diathesis or active gastrointestinal bleeding
Patients must have no clinical signs of heart failure and meet New York Heart Association functional classification I or II defined as:
- Class I - patients with no limitation of activities; they suffer no symptoms from ordinary activities
- Class II - patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion
- Patients must have an ECOG performance status of 0 or 1
- Patients must have a life expectancy of at least 3 months
- Patients must not be known to be human immunodeficiency virus (HIV) positive
Patients must not have other uncontrolled intercurrent illnesses excluding HBV or HCV, including, but not limited to: uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/addictive disorders that would limit compliance with study requirements
- Uncontrolled hypertension is defined as optimally treated baseline blood pressure that exceeds 150/90 mm Hg
- Patients must not be taking cytochrome P450 enzyme inducing drugs
- Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
- Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
- Patients must not have an allergy to iodine or gadolinium contrast that cannot be safely controlled with premedication
- Patient must be able to swallow pills, as study medications cannot be crushed
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- University of South Alabama Mitchell Cancer Institute
- Mayo Clinic in Arizona
- University of Arizona Cancer Center-Orange Grove Campus
- Banner University Medical Center - Tucson
- University of Arizona Cancer Center-North Campus
- John L McClellan Memorial Veterans Hospital
- University of Arkansas for Medical Sciences
- Marin Cancer Care Inc
- USC / Norris Comprehensive Cancer Center
- Saint Joseph Hospital - Orange
- Stanford Cancer Institute Palo Alto
- Zuckerberg San Francisco General Hospital
- UCSF Medical Center-Mount Zion
- University of Colorado Hospital
- UCHealth Memorial Hospital Central
- Porter Adventist Hospital
- Saint Mary's Hospital and Regional Medical Center
- Smilow Cancer Hospital Care Center at Saint Francis
- Yale University
- Beebe Medical Center
- Christiana Care Health System-Christiana Hospital
- Veterans Affairs Medical Center -Washington DC
- Mayo Clinic in Florida
- Lakeland Regional Health Hollis Cancer Center
- Emory University Hospital/Winship Cancer Institute
- Medical Center of Central Georgia
- Pali Momi Medical Center
- Hawaii Cancer Care Inc - Waterfront Plaza
- Queen's Medical Center
- University of Hawaii Cancer Center
- Hawaii Cancer Care Inc-Liliha
- Queen's Cancer Center - Kuakini
- The Cancer Center of Hawaii-Liliha
- Kapiolani Medical Center for Women and Children
- Castle Medical Center
- Wilcox Memorial Hospital and Kauai Medical Clinic
- Saint Alphonsus Cancer Care Center-Boise
- Saint Luke's Cancer Institute - Boise
- Saint Luke's Cancer Institute - Fruitland
- Saint Luke's Cancer Institute - Meridian
- Saint Luke's Cancer Institute - Nampa
- Saint Luke's Cancer Institute - Twin Falls
- Saint Joseph Medical Center
- Illinois CancerCare-Bloomington
- Graham Hospital Association
- Illinois CancerCare-Canton
- Illinois CancerCare-Carthage
- Memorial Hospital
- Hematology and Oncology Associates
- Northwestern University
- John H Stroger Jr Hospital of Cook County
- University of Illinois
- Swedish Covenant Hospital
- University of Chicago Comprehensive Cancer Center
- Heartland Cancer Research NCORP
- Eureka Hospital
- Illinois CancerCare-Eureka
- Saint Francis Hospital
- Illinois CancerCare-Galesburg
- Ingalls Memorial Hospital
- Illinois CancerCare-Havana
- Mason District Hospital
- Hematology Oncology Associates of Illinois-Highland Park
- Edward Hines Jr VA Hospital
- Hinsdale Hematology Oncology Associates Incorporated
- Midwest Center for Hematology Oncology
- Presence Saint Mary's Hospital
- Illinois CancerCare-Kewanee Clinic
- AMITA Health Adventist Medical Center
- AMG Libertyville - Oncology
- Illinois CancerCare-Macomb
- Mcdonough District Hospital
- Loyola University Medical Center
- Holy Family Medical Center
- Illinois CancerCare-Monmouth
- Illinois Cancer Specialists-Niles
- Bromenn Regional Medical Center
- Carle Cancer Institute Normal
- Illinois CancerCare-Community Cancer Center
- Illinois CancerCare-Ottawa Clinic
- Ottawa Regional Hospital and Healthcare Center
- Illinois CancerCare-Pekin
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Pekin Hospital
- Proctor Hospital
- Illinois CancerCare-Peoria
- Methodist Medical Center of Illinois
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Illinois Valley Hospital
- Illinois CancerCare-Princeton
- Perry Memorial Hospital
- West Suburban Medical Center
- Swedish American Hospital
- SwedishAmerican Regional Cancer Center/ACT
- Hematology Oncology Associates of Illinois - Skokie
- Illinois CancerCare-Spring Valley
- Medical Oncology and Hematology Associates-West Des Moines
- Iowa Methodist Medical Center
- Iowa-Wide Oncology Research Coalition NCORP
- Medical Oncology and Hematology Associates-Des Moines
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- HaysMed University of Kansas Health System
- Hutchinson Regional Medical Center
- University of Kansas Cancer Center-West
- University of Kansas Cancer Center
- Menorah Medical Center
- University of Kansas Cancer Center-Overland Park
- Saint Luke's South Hospital
- Ascension Via Christi - Pittsburg
- Kansas City NCI Community Oncology Research Program
- Salina Regional Health Center
- Advent Health - Shawnee Mission Medical Center
- University of Kansas Health System Saint Francis Campus
- University of Kentucky/Markey Cancer Center
- Ochsner Medical Center Jefferson
- LSU Health Sciences Center at Shreveport
- Saint Agnes Hospital
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Christiana Care - Union Hospital
- Tufts Medical Center
- Boston Medical Center
- Lahey Hospital and Medical Center
- Michigan Cancer Research Consortium NCORP
- Saint Joseph Mercy Hospital
- University of Michigan Comprehensive Cancer Center
- Beaumont Hospital - Dearborn
- Ascension Saint John Hospital
- Hurley Medical Center
- Genesys Regional Medical Center-West Flint Campus
- Allegiance Health
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Borgess Medical Center
- Sparrow Hospital
- Trinity Health Saint Mary Mercy Livonia Hospital
- UP Health System Marquette
- Saint Joseph Mercy Oakland
- Lake Huron Medical Center
- Ascension Saint Mary's Hospital
- Ascension Providence Hospitals - Southfield
- Saint John Macomb-Oakland Hospital
- Fairview Ridges Hospital
- Mercy Hospital
- Fairview Southdale Hospital
- Unity Hospital
- Hutchinson Area Health Care
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Hennepin County Medical Center
- North Memorial Medical Health Center
- Metro Minnesota Community Oncology Research Consortium
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Saint Francis Regional Medical Center
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- University of Mississippi Medical Center
- Veterans Administration
- Truman Medical Centers
- Saint Luke's Hospital of Kansas City
- Saint Joseph Health Center
- North Kansas City Hospital
- Heartland Hematology and Oncology Associates Incorporated
- Kansas City Veterans Affairs Medical Center
- The University of Kansas Cancer Center-South
- Research Medical Center
- University of Kansas Cancer Center - North
- University of Kansas Cancer Center - Lee's Summit
- Saint Luke's East - Lee's Summit
- Heartland Regional Medical Center
- Saint Joseph Oncology Inc
- Washington University School of Medicine
- Billings Clinic Cancer Center
- Northern Rockies Radiation Oncology Center
- Saint Vincent Healthcare
- Montana Cancer Consortium NCORP
- Saint Vincent Frontier Cancer Center
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- Berdeaux, Donald MD (UIA Investigator)
- Great Falls Clinic
- Northern Montana Hospital
- Saint Peter's Community Hospital
- Glacier Oncology PLLC
- Kalispell Medical Oncology
- Kalispell Regional Medical Center
- Montana Cancer Specialists
- Saint Patrick Hospital - Community Hospital
- Community Medical Hospital
- Guardian Oncology and Center for Wellness
- CHI Health Saint Francis
- Great Plains Health Callahan Cancer Center
- Nebraska Methodist Hospital
- University of Nebraska Medical Center
- Renown Regional Medical Center
- Dartmouth Hitchcock Medical Center
- Cooper Hospital University Medical Center
- Virtua Memorial
- Rutgers New Jersey Medical School
- MD Anderson Cancer Center at Cooper-Voorhees
- Virtua Voorhees
- University of New Mexico Cancer Center
- Veteran Affairs New York Harbor Healthcare System-Brooklyn Campus
- Maimonides Medical Center
- Mount Sinai Union Square
- Veterans Affairs New York Harbor Healthcare System-Manhattan Campus
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Mount Sinai West
- UNC Lineberger Comprehensive Cancer Center
- Novant Health Presbyterian Medical Center
- Rutherford Hospital
- Southeast Clinical Oncology Research Consortium NCORP
- Wake Forest University Health Sciences
- University of Cincinnati Cancer Center-UC Medical Center
- Case Western Reserve University
- MetroHealth Medical Center
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- ProMedica Flower Hospital
- University of Toledo
- Mercy Health - Saint Anne Hospital
- University of Oklahoma Health Sciences Center
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Legacy Mount Hood Medical Center
- Legacy Good Samaritan Hospital and Medical Center
- Legacy Emanuel Hospital and Health Center
- Legacy Meridian Park Hospital
- Saint Luke's University Hospital-Bethlehem Campus
- Geisinger Medical Center
- Thomas Jefferson University Hospital
- Fox Chase Cancer Center
- Einstein Medical Center Philadelphia
- Roger Williams Medical Center
- AnMed Health Cancer Center
- AnMed Health Hospital
- Medical University of South Carolina
- Prisma Health Cancer Institute - Easley
- Greenville Health System Cancer Institute-Andrews
- Saint Francis Hospital
- Prisma Health Cancer Institute - Greer
- Spartanburg Medical Center
- Jackson-Madison County General Hospital
- University of Tennessee - Knoxville
- The Don and Sybil Harrington Cancer Center
- Dell Seton Medical Center at The University of Texas
- University of Texas Medical Branch
- Huntsman Cancer Institute/University of Utah
- Bon Secours Saint Francis Medical Center
- Bon Secours Saint Mary's Hospital
- Hunter Holmes McGuire Veterans Administration Medical Center
- Virginia Commonwealth University/Massey Cancer Center
- MultiCare Auburn Medical Center
- Highline Medical Center-Main Campus
- Providence Regional Cancer System-Centralia
- Providence Regional Cancer Partnership
- Saint Francis Hospital
- Saint Clare Hospital
- Providence - Saint Peter Hospital
- MultiCare Good Samaritan Hospital
- Virginia Mason Medical Center
- Kaiser Permanente Washington
- MultiCare Allenmore Hospital
- MultiCare Tacoma General Hospital
- Northwest NCI Community Oncology Research Program
- Saint Joseph Medical Center
- Legacy Salmon Creek Hospital
- West Virginia University Healthcare
- Princeton Community Hospital
- University of Wisconsin Carbone Cancer Center
- Marshfield Medical Center-Marshfield
- Medical College of Wisconsin
- Rocky Mountain Oncology
- Welch Cancer Center
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm A (sorafenib and TACE)
Arm B (placebo and TACE)
Patients receive sorafenib tosylate at 400mg PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of sorafenib tosylate is reached, patients undergo TACE comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (this option may only be utilized for patients registered prior to addendum #3); conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising LC bead and doxorubicin. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Patients receive placebo PO BID in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached, patients undergo TACE as in Arm A.