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

Phase 3

Completed

Conditions: Hepatocellular Carcinoma
Unresectable Hepatocellular Carcinoma

Interventions: Drug: Cisplatin
Procedure: Computed Tomography
Drug: Doxorubicin Hydrochloride
Drug: Doxorubicin-Eluting Beads
Other: Laboratory Biomarker Analysis
Procedure: Magnetic Resonance Imaging
Drug: Mitomycin
Other: Pharmacological Study
Other: Placebo Administration
Drug: Sorafenib Tosylate

Registration Number: NCT01004978

Lead Sponsor: National Cancer Institute (NCI)

Brief 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.

Detailed 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 & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 235

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (sorafenib tosylate and TACE)	Computed Tomography	Patients receive sorafenib tosylate 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 (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 CT and MRI on study.
Arm I (sorafenib tosylate and TACE)	Doxorubicin-Eluting Beads	Patients receive sorafenib tosylate 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 (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 CT and MRI on study.
Arm I (sorafenib tosylate and TACE)	Laboratory Biomarker Analysis	Patients receive sorafenib tosylate 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 (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 CT and MRI on study.
Arm I (sorafenib tosylate and TACE)	Magnetic Resonance Imaging	Patients receive sorafenib tosylate 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 (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 CT and MRI on study.
Arm I (sorafenib tosylate and TACE)	Pharmacological Study	Patients receive sorafenib tosylate 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 (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 CT and MRI on study.
Arm II (placebo and TACE)	Laboratory Biomarker Analysis	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.
Arm II (placebo and TACE)	Computed Tomography	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.
Arm II (placebo and TACE)	Doxorubicin-Eluting Beads	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.
Arm II (placebo and TACE)	Magnetic Resonance Imaging	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.
Arm II (placebo and TACE)	Mitomycin	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.
Arm II (placebo and TACE)	Pharmacological Study	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.
Arm II (placebo and TACE)	Placebo Administration	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.
Arm I (sorafenib tosylate and TACE)	Sorafenib Tosylate	Patients receive sorafenib tosylate 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 (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 CT and MRI on study.
Arm I (sorafenib tosylate and TACE)	Cisplatin	Patients receive sorafenib tosylate 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 (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 CT and MRI on study.
Arm I (sorafenib tosylate and TACE)	Doxorubicin Hydrochloride	Patients receive sorafenib tosylate 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 (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 CT and MRI on study.
Arm I (sorafenib tosylate and TACE)	Mitomycin	Patients receive sorafenib tosylate 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 (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 CT and MRI on study.
Arm II (placebo and TACE)	Cisplatin	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.
Arm II (placebo and TACE)	Doxorubicin Hydrochloride	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.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	Assessed 4 months after first chemoembolization, 8 months after first chemoembolization, then every 8 weeks, up to 4 years	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Assessed every 3 months for 2 years and then every 6 months for 2 years	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.
Progression-free Survival (PFS) 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	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.
Progression-free Survival (PFS) 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	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.

Trial Locations

Locations (278): Illinois CancerCare-Havana
🇺🇸
Havana, Illinois, United States
Saint Agnes Hospital
🇺🇸
Baltimore, Maryland, United States
Thomas Jefferson University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Illinois CancerCare-Monmouth
🇺🇸
Monmouth, Illinois, United States
Midwest Center for Hematology Oncology
🇺🇸
Joliet, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸
Kewanee, Illinois, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Hinsdale Hematology Oncology Associates Incorporated
🇺🇸
Hinsdale, Illinois, United States
Hematology Oncology Associates of Illinois-Highland Park
🇺🇸
Highland Park, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸
Macomb, Illinois, United States
Presence Saint Mary's Hospital
🇺🇸
Kankakee, Illinois, United States
Proctor Hospital
🇺🇸
Peoria, Illinois, United States
University of Kansas Cancer Center
🇺🇸
Kansas City, Kansas, United States
SwedishAmerican Regional Cancer Center/ACT
🇺🇸
Rockford, Illinois, United States
AMITA Health Adventist Medical Center
🇺🇸
La Grange, Illinois, United States
Edward Hines Jr VA Hospital
🇺🇸
Hines, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸
Peoria, Illinois, United States
Carle Cancer Institute Normal
🇺🇸
Normal, Illinois, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸
Ottawa, Illinois, United States
Medical Oncology and Hematology Associates-West Des Moines
🇺🇸
Clive, Iowa, United States
Mcdonough District Hospital
🇺🇸
Macomb, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸
Pekin, Illinois, United States
Illinois Cancer Specialists-Niles
🇺🇸
Niles, Illinois, United States
Kalispell Medical Oncology
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Kalispell, Montana, United States
Kalispell Regional Medical Center
🇺🇸
Kalispell, Montana, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸
Butte, Montana, United States
Veteran Affairs New York Harbor Healthcare System-Brooklyn Campus
🇺🇸
Brooklyn, New York, United States
Mount Sinai West
🇺🇸
New York, New York, United States
Rutherford Hospital
🇺🇸
Rutherfordton, North Carolina, United States
Saint Peter's Community Hospital
🇺🇸
Helena, Montana, United States
Great Falls Clinic
🇺🇸
Great Falls, Montana, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Renown Regional Medical Center
🇺🇸
Reno, Nevada, United States
Cooper Hospital University Medical Center
🇺🇸
Camden, New Jersey, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
🇺🇸
Tulsa, Oklahoma, United States
Northern Montana Hospital
🇺🇸
Havre, Montana, United States
Great Plains Health Callahan Cancer Center
🇺🇸
North Platte, Nebraska, United States
Rutgers New Jersey Medical School
🇺🇸
Newark, New Jersey, United States
Virtua Voorhees
🇺🇸
Voorhees, New Jersey, United States
Novant Health Presbyterian Medical Center
🇺🇸
Charlotte, North Carolina, United States
Saint Clare Hospital
🇺🇸
Lakewood, Washington, United States
University of Texas Medical Branch
🇺🇸
Galveston, Texas, United States
Einstein Medical Center Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
MultiCare Good Samaritan Hospital
🇺🇸
Puyallup, Washington, United States
Providence - Saint Peter Hospital
🇺🇸
Olympia, Washington, United States
MultiCare Auburn Medical Center
🇺🇸
Auburn, Washington, United States
MultiCare Tacoma General Hospital
🇺🇸
Tacoma, Washington, United States
Legacy Salmon Creek Hospital
🇺🇸
Vancouver, Washington, United States
Providence Regional Cancer System-Centralia
🇺🇸
Centralia, Washington, United States
Princeton Community Hospital
🇺🇸
Princeton, West Virginia, United States
Providence Regional Cancer Partnership
🇺🇸
Everett, Washington, United States
MetroHealth Medical Center
🇺🇸
Cleveland, Ohio, United States
University of Illinois
🇺🇸
Chicago, Illinois, United States
Swedish Covenant Hospital
🇺🇸
Chicago, Illinois, United States
Tufts Medical Center
🇺🇸
Boston, Massachusetts, United States
Virginia Mason Medical Center
🇺🇸
Seattle, Washington, United States
Kaiser Permanente Washington
🇺🇸
Seattle, Washington, United States
University of Cincinnati Cancer Center-UC Medical Center
🇺🇸
Cincinnati, Ohio, United States
Zuckerberg San Francisco General Hospital
🇺🇸
San Francisco, California, United States
UCSF Medical Center-Mount Zion
🇺🇸
San Francisco, California, United States
Abbott-Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
Hennepin County Medical Center
🇺🇸
Minneapolis, Minnesota, United States
Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
Advent Health - Shawnee Mission Medical Center
🇺🇸
Shawnee Mission, Kansas, United States
Menorah Medical Center
🇺🇸
Overland Park, Kansas, United States
Salina Regional Health Center
🇺🇸
Salina, Kansas, United States
Welch Cancer Center
🇺🇸
Sheridan, Wyoming, United States
Kansas City NCI Community Oncology Research Program
🇺🇸
Prairie Village, Kansas, United States
University of Kansas Cancer Center-West
🇺🇸
Kansas City, Kansas, United States
Rocky Mountain Oncology
🇺🇸
Casper, Wyoming, United States
University of Kansas Cancer Center-Overland Park
🇺🇸
Overland Park, Kansas, United States
Saint Luke's South Hospital
🇺🇸
Overland Park, Kansas, United States
Boston Medical Center
🇺🇸
Boston, Massachusetts, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Ascension Saint John Hospital
🇺🇸
Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Legacy Emanuel Hospital and Health Center
🇺🇸
Portland, Oregon, United States
Veterans Affairs New York Harbor Healthcare System-Manhattan Campus
🇺🇸
New York, New York, United States
Fairview Southdale Hospital
🇺🇸
Edina, Minnesota, United States
Ridgeview Medical Center
🇺🇸
Waconia, Minnesota, United States
Illinois CancerCare-Community Cancer Center
🇺🇸
Normal, Illinois, United States
Medical Center of Central Georgia
🇺🇸
Macon, Georgia, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸
Lebanon, New Hampshire, United States
ProMedica Flower Hospital
🇺🇸
Sylvania, Ohio, United States
Legacy Mount Hood Medical Center
🇺🇸
Gresham, Oregon, United States
Prisma Health Cancer Institute - Easley
🇺🇸
Easley, South Carolina, United States
Prisma Health Cancer Institute - Greer
🇺🇸
Greer, South Carolina, United States
Spartanburg Medical Center
🇺🇸
Spartanburg, South Carolina, United States
University of Alabama at Birmingham Cancer Center
🇺🇸
Birmingham, Alabama, United States
University of South Alabama Mitchell Cancer Institute
🇺🇸
Mobile, Alabama, United States
University of Arizona Cancer Center-Orange Grove Campus
🇺🇸
Tucson, Arizona, United States
Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Banner University Medical Center - Tucson
🇺🇸
Tucson, Arizona, United States
USC / Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
John L McClellan Memorial Veterans Hospital
🇺🇸
Little Rock, Arkansas, United States
Marin Cancer Care Inc
🇺🇸
Greenbrae, California, United States
Saint Joseph Hospital - Orange
🇺🇸
Orange, California, United States
Stanford Cancer Institute Palo Alto
🇺🇸
Palo Alto, California, United States
Porter Adventist Hospital
🇺🇸
Denver, Colorado, United States
UCHealth Memorial Hospital Central
🇺🇸
Colorado Springs, Colorado, United States
Saint Mary's Hospital and Regional Medical Center
🇺🇸
Grand Junction, Colorado, United States
Smilow Cancer Hospital Care Center at Saint Francis
🇺🇸
Hartford, Connecticut, United States
Beebe Medical Center
🇺🇸
Lewes, Delaware, United States
Christiana Care Health System-Christiana Hospital
🇺🇸
Newark, Delaware, United States
Veterans Affairs Medical Center -Washington DC
🇺🇸
Washington, District of Columbia, United States
Mayo Clinic in Florida
🇺🇸
Jacksonville, Florida, United States
Pali Momi Medical Center
🇺🇸
'Aiea, Hawaii, United States
Lakeland Regional Health Hollis Cancer Center
🇺🇸
Lakeland, Florida, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
Saint Luke's Cancer Institute - Boise
🇺🇸
Boise, Idaho, United States
Castle Medical Center
🇺🇸
Kailua, Hawaii, United States
Wilcox Memorial Hospital and Kauai Medical Clinic
🇺🇸
Lihue, Hawaii, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸
Boise, Idaho, United States
Saint Luke's Cancer Institute - Fruitland
🇺🇸
Fruitland, Idaho, United States
Saint Luke's Cancer Institute - Meridian
🇺🇸
Meridian, Idaho, United States
Saint Luke's Cancer Institute - Nampa
🇺🇸
Nampa, Idaho, United States
Illinois CancerCare-Bloomington
🇺🇸
Bloomington, Illinois, United States
Graham Hospital Association
🇺🇸
Canton, Illinois, United States
Hematology and Oncology Associates
🇺🇸
Chicago, Illinois, United States
Memorial Hospital
🇺🇸
Carthage, Illinois, United States
Illinois CancerCare-Canton
🇺🇸
Canton, Illinois, United States
Illinois CancerCare-Carthage
🇺🇸
Carthage, Illinois, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Eureka Hospital
🇺🇸
Eureka, Illinois, United States
Heartland Cancer Research NCORP
🇺🇸
Decatur, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸
Eureka, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸
Galesburg, Illinois, United States
Ingalls Memorial Hospital
🇺🇸
Harvey, Illinois, United States
AMG Libertyville - Oncology
🇺🇸
Libertyville, Illinois, United States
Holy Family Medical Center
🇺🇸
Monmouth, Illinois, United States
Bromenn Regional Medical Center
🇺🇸
Normal, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸
Ottawa, 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-Peru
🇺🇸
Peru, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸
Peoria, Illinois, United States
OSF Saint Francis Medical Center
🇺🇸
Peoria, Illinois, United States
Perry Memorial Hospital
🇺🇸
Princeton, Illinois, United States
Illinois Valley Hospital
🇺🇸
Peru, Illinois, United States
West Suburban Medical Center
🇺🇸
River Forest, Illinois, United States
Illinois CancerCare-Princeton
🇺🇸
Princeton, Illinois, United States
Swedish American Hospital
🇺🇸
Rockford, Illinois, United States
Hematology Oncology Associates of Illinois - Skokie
🇺🇸
Skokie, Illinois, United States
Illinois CancerCare-Spring Valley
🇺🇸
Spring Valley, Illinois, United States
HaysMed University of Kansas Health System
🇺🇸
Hays, Kansas, United States
Hutchinson Regional Medical Center
🇺🇸
Hutchinson, Kansas, United States
University of Kansas Health System Saint Francis Campus
🇺🇸
Topeka, Kansas, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸
Baltimore, Maryland, United States
Christiana Care - Union Hospital
🇺🇸
Elkton, Maryland, United States
Lahey Hospital and Medical Center
🇺🇸
Burlington, Massachusetts, United States
Beaumont Hospital - Dearborn
🇺🇸
Dearborn, Michigan, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Genesys Regional Medical Center-West Flint Campus
🇺🇸
Flint, Michigan, United States
Allegiance Health
🇺🇸
Jackson, Michigan, United States
West Michigan Cancer Center
🇺🇸
Kalamazoo, Michigan, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
Borgess Medical Center
🇺🇸
Kalamazoo, Michigan, United States
Sparrow Hospital
🇺🇸
Lansing, Michigan, United States
UP Health System Marquette
🇺🇸
Marquette, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
🇺🇸
Livonia, Michigan, United States
Ascension Saint Mary's Hospital
🇺🇸
Saginaw, Michigan, United States
Saint Joseph Mercy Oakland
🇺🇸
Pontiac, Michigan, United States
Lake Huron Medical Center
🇺🇸
Port Huron, Michigan, United States
Ascension Providence Hospitals - Southfield
🇺🇸
Southfield, Michigan, United States
Fairview Ridges Hospital
🇺🇸
Burnsville, Minnesota, United States
Mercy Hospital
🇺🇸
Coon Rapids, Minnesota, United States
Unity Hospital
🇺🇸
Fridley, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸
Maplewood, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸
Maplewood, Minnesota, United States
Hutchinson Area Health Care
🇺🇸
Hutchinson, Minnesota, 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
Saint Francis Regional Medical Center
🇺🇸
Shakopee, Minnesota, United States
Rice Memorial Hospital
🇺🇸
Willmar, Minnesota, United States
Veterans Administration
🇺🇸
Columbia, Missouri, United States
University of Kansas Cancer Center - Lee's Summit
🇺🇸
Lee's Summit, Missouri, United States
Heartland Regional Medical Center
🇺🇸
Saint Joseph, Missouri, United States
Saint Luke's East - Lee's Summit
🇺🇸
Lee's Summit, Missouri, 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 Healthcare
🇺🇸
Billings, Montana, United States
Saint Vincent Frontier Cancer Center
🇺🇸
Billings, Montana, United States
Benefis Healthcare- Sletten Cancer Institute
🇺🇸
Great Falls, Montana, United States
Bozeman Deaconess Hospital
🇺🇸
Bozeman, Montana, United States
Glacier Oncology PLLC
🇺🇸
Kalispell, Montana, United States
Montana Cancer Specialists
🇺🇸
Missoula, Montana, United States
Saint Patrick Hospital - Community Hospital
🇺🇸
Missoula, Montana, United States
CHI Health Saint Francis
🇺🇸
Grand Island, Nebraska, United States
MD Anderson Cancer Center at Cooper-Voorhees
🇺🇸
Voorhees, New Jersey, United States
Virtua Memorial
🇺🇸
Mount Holly, New Jersey, 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
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Mercy Health - Saint Anne Hospital
🇺🇸
Toledo, Ohio, United States
Legacy Good Samaritan Hospital and Medical Center
🇺🇸
Portland, Oregon, United States
Saint Luke's University Hospital-Bethlehem Campus
🇺🇸
Bethlehem, Pennsylvania, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Roger Williams Medical Center
🇺🇸
Providence, Rhode Island, United States
University of Toledo
🇺🇸
Toledo, Ohio, United States
The Don and Sybil Harrington Cancer Center
🇺🇸
Amarillo, Texas, United States
University of Tennessee - Knoxville
🇺🇸
Knoxville, Tennessee, United States
Bon Secours Saint Francis Medical Center
🇺🇸
Midlothian, Virginia, United States
Highline Medical Center-Main Campus
🇺🇸
Burien, Washington, United States
Northwest NCI Community Oncology Research Program
🇺🇸
Tacoma, Washington, United States
West Virginia University Healthcare
🇺🇸
Morgantown, West Virginia, United States
Marshfield Medical Center-Marshfield
🇺🇸
Marshfield, Wisconsin, United States
North Memorial Medical Health Center
🇺🇸
Robbinsdale, Minnesota, United States
University of Arizona Cancer Center-North Campus
🇺🇸
Tucson, Arizona, United States
John H Stroger Jr Hospital of Cook County
🇺🇸
Chicago, Illinois, United States
Saint Luke's Cancer Institute - Twin Falls
🇺🇸
Twin Falls, Idaho, United States
Saint Joseph Medical Center
🇺🇸
Tacoma, Washington, United States
Maimonides Medical Center
🇺🇸
Brooklyn, New York, United States
Saint Francis Hospital
🇺🇸
Federal Way, Washington, United States
Mason District Hospital
🇺🇸
Havana, Illinois, United States
MultiCare Allenmore Hospital
🇺🇸
Tacoma, Washington, United States
AnMed Health Cancer Center
🇺🇸
Anderson, South Carolina, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸
Woodbury, Minnesota, United States
Saint Joseph Oncology Inc
🇺🇸
Saint Joseph, Missouri, United States
Ohio State University Comprehensive Cancer Center
🇺🇸
Columbus, Ohio, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
Legacy Meridian Park Hospital
🇺🇸
Tualatin, Oregon, United States
Greenville Health System Cancer Institute-Andrews
🇺🇸
Greenville, South Carolina, United States
UCHealth University of Colorado Hospital
🇺🇸
Aurora, Colorado, 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
Nebraska Methodist Hospital
🇺🇸
Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, 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
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Saint John Macomb-Oakland Hospital
🇺🇸
Warren, Michigan, United States
Jackson-Madison County General Hospital
🇺🇸
Jackson, Tennessee, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
AnMed Health Hospital
🇺🇸
Anderson, South Carolina, United States
LSU Health Sciences Center at Shreveport
🇺🇸
Shreveport, Louisiana, United States
Guardian Oncology and Center for Wellness
🇺🇸
Missoula, Montana, United States
Berdeaux, Donald MD (UIA Investigator)
🇺🇸
Great Falls, Montana, United States
Community Medical Hospital
🇺🇸
Missoula, Montana, United States
Ochsner Medical Center Jefferson
🇺🇸
New Orleans, Louisiana, United States
Bon Secours Saint Mary's Hospital
🇺🇸
Richmond, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸
Richmond, Virginia, United States
Hunter Holmes McGuire Veterans Administration Medical Center
🇺🇸
Richmond, Virginia, United States
Truman Medical Centers
🇺🇸
Kansas City, Missouri, United States
Saint Luke's Hospital of Kansas City
🇺🇸
Kansas City, Missouri, United States
University of Kansas Cancer Center - North
🇺🇸
Kansas City, Missouri, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸
Chapel Hill, North Carolina, United States
Saint Joseph Health Center
🇺🇸
Kansas City, Missouri, United States
North Kansas City Hospital
🇺🇸
Kansas City, Missouri, United States
Heartland Hematology and Oncology Associates Incorporated
🇺🇸
Kansas City, Missouri, United States
The University of Kansas Cancer Center-South
🇺🇸
Kansas City, Missouri, United States
Kansas City Veterans Affairs Medical Center
🇺🇸
Kansas City, Missouri, United States
Research Medical Center
🇺🇸
Kansas City, Missouri, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Hawaii Cancer Care Inc - Waterfront Plaza
🇺🇸
Honolulu, Hawaii, United States
Queen's Medical Center
🇺🇸
Honolulu, Hawaii, United States
University of Hawaii Cancer Center
🇺🇸
Honolulu, Hawaii, United States
Hawaii Cancer Care Inc-Liliha
🇺🇸
Honolulu, Hawaii, United States
Queen's Cancer Center - Kuakini
🇺🇸
Honolulu, Hawaii, United States
The Cancer Center of Hawaii-Liliha
🇺🇸
Honolulu, Hawaii, United States
Kapiolani Medical Center for Women and Children
🇺🇸
Honolulu, Hawaii, United States
Dell Seton Medical Center at The University of Texas
🇺🇸
Austin, Texas, 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
Iowa Lutheran Hospital
🇺🇸
Des Moines, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸
Lexington, Kentucky, United States
University of Wisconsin Carbone Cancer Center
🇺🇸
Madison, Wisconsin, United States
Ascension Via Christi - Pittsburg
🇺🇸
Pittsburg, Kansas, United States