Chemoembolization With or Without Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

Hepatocellular Carcinoma Clinical Trial

Official title:

A Phase III Randomized, Double-Blind Trial of Chemoembolization With or Without Sorafenib in Unresectable Hepatocellular Carcinoma (HCC) in Patients With and Without Vascular Invasion

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01004978
• Other study ID #: NCI-2011-01981
• Secondary ID: NCI-2011-01981EC
• Status: Completed
• Phase: Phase 3
• Start date: October 28, 2009
• Est. completion date: December 21, 2022

Study information

• Verified date: November 2023
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies chemoembolization and sorafenib tosylate to see how well they work compared with chemoembolization alone in treating patients with liver cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as doxorubicin hydrochloride, mitomycin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Chemoembolization kills tumor cells by carrying drugs directly into blood vessels near the tumor and then blocking the blood flow to allow a higher concentration of the drug to reach the tumor for a longer period of time. Kinase inhibitors, such as sorafenib tosylate may stop the growth of tumor cells by blocking the action of an abnormal protein that signals cancer cells to multiply. It is not yet known whether giving chemoembolization together with sorafenib tosylate is more effective than chemoembolization alone in treating patients with liver cancer.

Description:

PRIMARY OBJECTIVE:

I. To compare progression-free survival (PFS) of chemoembolization alone to sorafenib (sorafenib tosylate) in combination with chemoembolization.

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) of chemoembolization alone to sorafenib in combination with chemoembolization.

II. To evaluate extra-hepatic versus intra-hepatic patterns of failure. III. To determine the rates of toxicity related to sorafenib in combination with chemoembolization.

TERTIARY OBJECTIVES:

I. To analyze the pharmacogenetic and pharmacokinetic properties of sorafenib including angiogenesis, monooxygenases, polymorphisms and multidrug resistance (MDR).

II. Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) secondary imaging objective: site versus (vs.) central evaluation of PFS.

III. To determine the inter-reader concordance for response characterization at four and eight months by the European Association for the Study of Liver (EASL) criteria.

IV. To determine the value of objective tumor response at four and eight months by the EASL criteria to predict PFS (by Response Evaluation Criteria in Solid Tumors [RECIST]) and OS.

V. To evaluate the effects of intra-hepatic vs. extra-hepatic progression on OS.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive sorafenib tosylate orally (PO) twice daily (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 transarterial chemoembolization (TACE) comprising doxorubicin hydrochloride, mitomycin C, and cisplatin (closed to accrual as of 10/1/2010); conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising doxorubicin-eluting beads. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and magnetic resonance imaging (MRI) on study.

ARM II: 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 I. Patients also undergo CT and MRI on study.

MAINTENANCE THERAPY: After completion of chemoembolization, patients receive sorafenib tosylate or placebo as in Arm I and II in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 235
• Est. completion date: December 21, 2022
• Est. primary completion date: February 11, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Eastern Cooperative Oncology Group (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

• Age >= 18 years

• 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Unresectable Hepatocellular Carcinoma

Intervention

Drug:
• Cisplatin
Undergo TACE

Procedure:
• Computed Tomography
Undergo CT scan

Drug:
• Doxorubicin Hydrochloride
Undergo TACE
• Doxorubicin-Eluting Beads
Undergo TACE

Other:
• Laboratory Biomarker Analysis
Correlative studies

Procedure:
• Magnetic Resonance Imaging
Undergo MRI

Drug:
• Mitomycin
Undergo TACE

Other:
• Pharmacological Study
Correlative studies
• Placebo Administration
Given PO

Drug:
• Sorafenib Tosylate
Given PO

Locations

Country	Name	City	State
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	AnMed Health Hospital	Anderson	South Carolina
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	MultiCare Auburn Medical Center	Auburn	Washington
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	Dell Seton Medical Center at The University of Texas	Austin	Texas
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Boston Medical Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Maimonides Medical Center	Brooklyn	New York
United States	Veteran Affairs New York Harbor Healthcare System-Brooklyn Campus	Brooklyn	New York
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Graham Hospital Association	Canton	Illinois
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Swedish Covenant Hospital	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Veterans Administration	Columbia	Missouri
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Saint Francis Hospital	Evanston	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Saint Francis Hospital	Federal Way	Washington
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	University of Texas Medical Branch	Galveston	Texas
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Marin Cancer Care Inc	Greenbrae	California
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Northern Montana Hospital	Havre	Montana
United States	HaysMed University of Kansas Health System	Hays	Kansas
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois
United States	Edward Hines Jr VA Hospital	Hines	Illinois
United States	Hinsdale Hematology Oncology Associates Incorporated	Hinsdale	Illinois
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Hutchinson Regional Medical Center	Hutchinson	Kansas
United States	Allegiance Health	Jackson	Michigan
United States	Jackson-Madison County General Hospital	Jackson	Tennessee
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Midwest Center for Hematology Oncology	Joliet	Illinois
United States	Castle Medical Center	Kailua	Hawaii
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Joseph Health Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	The University of Kansas Cancer Center-South	Kansas City	Missouri
United States	Truman Medical Centers	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	University of Kansas Cancer Center-West	Kansas City	Kansas
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	AMITA Health Adventist Medical Center	La Grange	Illinois
United States	Lakeland Regional Health Hollis Cancer Center	Lakeland	Florida
United States	Saint Clare Hospital	Lakewood	Washington
United States	Sparrow Hospital	Lansing	Michigan
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Beebe Medical Center	Lewes	Delaware
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	John L McClellan Memorial Veterans Hospital	Little Rock	Arkansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Medical Center of Central Georgia	Macon	Georgia
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	UP Health System Marquette	Marquette	Michigan
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Bon Secours Saint Francis Medical Center	Midlothian	Virginia
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Community Medical Hospital	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Holy Family Medical Center	Monmouth	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Yale University	New Haven	Connecticut
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Mount Sinai Union Square	New York	New York
United States	Mount Sinai West	New York	New York
United States	Veterans Affairs New York Harbor Healthcare System-Manhattan Campus	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Carle Cancer Institute Normal	Normal	Illinois
United States	Illinois CancerCare-Community Cancer Center	Normal	Illinois
United States	Great Plains Health Callahan Cancer Center	North Platte	Nebraska
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Providence - Saint Peter Hospital	Olympia	Washington
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Joseph Hospital - Orange	Orange	California
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Einstein Medical Center Philadelphia	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Princeton Community Hospital	Princeton	West Virginia
United States	Roger Williams Medical Center	Providence	Rhode Island
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Renown Regional Medical Center	Reno	Nevada
United States	Bon Secours Saint Mary's Hospital	Richmond	Virginia
United States	Hunter Holmes McGuire Veterans Administration Medical Center	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	West Suburban Medical Center	River Forest	Illinois
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Swedish American Hospital	Rockford	Illinois
United States	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Saint Joseph Oncology Inc	Saint Joseph	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	Zuckerberg San Francisco General Hospital	San Francisco	California
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Advent Health - Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	Welch Cancer Center	Sheridan	Wyoming
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	MultiCare Allenmore Hospital	Tacoma	Washington
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest NCI Community Oncology Research Program	Tacoma	Washington
United States	Saint Joseph Medical Center	Tacoma	Washington
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Veterans Affairs Medical Center -Washington DC	Washington	District of Columbia
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Southeast Clinical Oncology Research Consortium NCORP	Winston-Salem	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacogenetic and Pharmacokinetic Properties of Sorafenib Including Angiogenesis, Monooxygenases, Polymorphisms and Multidrug Resistance Mutation (MDR)	This analysis will be performed across a few ECOG-ACRIN studies of sorafenib to evaluate the association between genotypes that are related with sorafenib activity and clinical outcomes.	Assessed at baseline, days 1, 8 and 15 of cycle 1 sorafenib, 3-5 days prior to 2nd and 3rd TACE
Other	Inter-reader Concordance for Response by EASL (European Association for the Study of the Liver) Criteria	Response was determined using the European Association for the Study of the Liver (EASL) criteria, which was recommended as an alternative to RECIST for grading therapeutic response of advanced hepatocellular carcinoma (HCC). The EASL criteria use the longest dimension of enhancing tumor as the primary metric for gauging tumor response. The Kappa statistics will be applied to assess agreement between readers.	at 4 months and 8 months Assessed at 4 months and 8 months following initial chemoembolization
Other	Association Between Objective Tumor Response by EASL Criteria and PFS as Well as OS	PFS is defined to be the time from randomization to progression or death without evidence of progression. For cases without documentation of progression, follow-up will be censored at the date of last disease assessment without progression, unless death occurs within 4 months following the date last known progression-free, in which case the death will be counted as an event.; Progression is assessed per Solid Tumor Response Criteria (RECIST) and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions.; OS is defined as time from randomization to death or date last known alive. Response is assessed at 4 and 8 months by EASL criteria.	Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years
Other	To Evaluate the Effects of Intra-hepatic vs. Extra-hepatic Progression on OS.	Progression is assessed per Solid Tumor Response Criteria (RECIST) and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions.; For patients with progressive disease, the progression was classified as either intra- or extra-hepatic or both intra- and extra-hepatic.; OS is defined as the time from randomization to death or date last known alive.	Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years
Primary	Progression-free Survival (PFS)	PFS is defined to be the time from randomization to progression or death without evidence of progression. For cases without documentation of progression, follow-up will be censored at the date of last disease assessment without progression, unless death occurs within 4 months following the date last known progression-free, in which case the death will be counted as an event.; Progression is assessed per Solid Tumor Response Criteria (RECIST) and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions.	Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years
Secondary	Overall Survival (OS)	Overall survival (OS) is defined as time from randomization to death from any cause, censoring cases who had not died at the date last known alive.	Assessed every 3 months for 2 years and then every 6 months for 2 years
Secondary	Progression-free Survival (PFS) Among Patients With Extra-hepatic Progression	PFS is defined to be the time from randomization to progression or death without evidence of progression.; Progression is assessed per Solid Tumor Response Criteria (RECIST) and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions.; For patients with progressive disease, the progression was classified as either intra- or extra-hepatic or both intra- and extra-hepatic. Patients with both intra- and extra-hepatic progression were considered as having extra-hepatic progression. This analysis was performed among patients with extra-hepatic progression.	Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years
Secondary	Progression-free Survival (PFS) Among Patients With Intra-hepatic Progression	PFS is defined to be the time from randomization to progression or death without evidence of progression.; Progression is assessed per Solid Tumor Response Criteria (RECIST) and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions.; For patients with progressive disease, the progression was classified as either intra- or extra-hepatic or both intra- and extra-hepatic. This analysis was performed among patients with intra-hepatic progression.	Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years