Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy

Randomized Phase III Trial Comparing Everolimus Versus Everolimus Plus Bevacizumab for Advanced Renal Cell Carcinoma Progressing After Treatment With Tyrosine Kinase Inhibitors

This randomized phase III trial studies giving everolimus together with bevacizumab to see how well it works compared to everolimus alone in treating patients with advanced kidney cancer that progressed after first-line therapy. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can interfere with tumor growth by blocking the ability of tumor cells to grow and spread. Everolimus and bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with bevacizumab is better than everolimus alone in treating patients with advanced kidney cancer that has progressed after first-line therapy.

Study Overview

• Status: Terminated
• Conditions: Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Everolimus; Biological: Bevacizumab

Detailed Description

PRIMARY OBJECTIVES:

l. To compare the overall survival of patients receiving bevacizumab plus everolimus and everolimus alone among patients with advanced renal cell carcinoma progressing after first line vascular epidermal growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI) treatment.

SECONDARY OBJECTIVES:

I. To compare the progression-free survival and proportion who experience an objective response (defined as complete clinical response [cCR] + partial response [PR]) in patients with advanced renal cell carcinoma receiving bevacizumab plus everolimus and everolimus alone.

II. To compare grade 3 or higher toxicity in patients receiving each treatment regimen.

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

ARM I: Patients receive everolimus orally (PO) once daily (QD) on days 1-28.

ARM II: Patients receive everolimus PO QD on days 1-28 and bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8 weeks until disease progression and then every 6 months for up to 5.5 years.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Fowler Family Center for Cancer Care
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Anaheim, California, United States, 92806
      • Kaiser Permanente-Anaheim
    • Antioch, California, United States, 94531
      • Kaiser Permanente-Deer Valley Medical Center
    • Arroyo Grande, California, United States, 93420
      • PCR Oncology
    • Baldwin Park, California, United States, 91706
      • Kaiser Permanente-Baldwin Park
    • Bellflower, California, United States, 90706
      • Kaiser Permanente-Bellflower
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center-Herrick Campus
    • Burlingame, California, United States, 94010
      • Mills-Peninsula Medical Center
    • Castro Valley, California, United States, 94546
      • East Bay Radiation Oncology Center
    • Castro Valley, California, United States, 94546
      • Valley Medical Oncology Consultants-Castro Valley
    • Emeryville, California, United States, 94608
      • Bay Area Breast Surgeons Inc
    • Emeryville, California, United States, 94608
      • Epic Care Partners in Cancer Care
    • Fontana, California, United States, 92335
      • Kaiser Permanente-Fontana
    • Fremont, California, United States, 94538
      • Kaiser Permanente-Fremont
    • Fremont, California, United States, 94538
      • Valley Medical Oncology Consultants-Fremont
    • Fresno, California, United States, 93720
      • Kaiser Permanente-Fresno
    • Harbor City, California, United States, 90710
      • Kaiser Permanente - Harbor City
    • Irvine, California, United States, 92618
      • Kaiser Permanente-Irvine
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90034
      • Kaiser Permanente-Cadillac
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Modesto, California, United States, 95355
      • Memorial Medical Center
    • Mountain View, California, United States, 94040
      • El Camino Hospital
    • Novato, California, United States, 94945
      • Sutter Cancer Research Consortium
    • Oakland, California, United States, 94611
      • Kaiser Permanente-Oakland
    • Oakland, California, United States, 94611
      • Kaiser Permanente Oakland-Broadway
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94609
      • Hematology and Oncology Associates-Oakland
    • Oakland, California, United States, 94602
      • Highland General Hospital
    • Oakland, California, United States, 94609
      • Tom K Lee Inc
    • Oakland, California, United States, 94609
      • Bay Area Tumor Institute
    • Panorama City, California, United States, 91402
      • Kaiser Permanente - Panorama City
    • Rancho Cordova, California, United States, 95670
      • Kaiser Permanente-Rancho Cordova Cancer Center
    • Redwood City, California, United States, 94063
      • Kaiser Permanente-Redwood City
    • Richmond, California, United States, 94801
      • Kaiser Permanente-Richmond
    • Riverside, California, United States, 92505
      • Kaiser Permanente-Riverside
    • Rohnert Park, California, United States, 94928
      • Rohnert Park Cancer Center
    • Roseville, California, United States, 95678
      • The Permanente Medical Group-Roseville Radiation Oncology
    • Roseville, California, United States, 95661
      • Kaiser Permanente-Roseville
    • Sacramento, California, United States, 95823
      • Kaiser Permanente-South Sacramento
    • Sacramento, California, United States, 95823
      • South Sacramento Cancer Center
    • Sacramento, California, United States, 95825
      • Kaiser Permanente - Sacramento
    • San Diego, California, United States, 92120
      • Kaiser Permanente-San Diego Zion
    • San Diego, California, United States, 92108
      • Kaiser Permanente-San Diego Mission
    • San Francisco, California, United States, 94115
      • Kaiser Permanente-San Francisco
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center-Pacific Campus
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital
    • San Jose, California, United States, 95119
      • Kaiser Permanente-Santa Teresa-San Jose
    • San Leandro, California, United States, 94577
      • Kaiser Permanente San Leandro
    • San Marcos, California, United States, 92078
      • Kaiser Permanente-San Marcos
    • San Pablo, California, United States, 94806
      • Doctors Medical Center- JC Robinson Regional Cancer Center
    • San Rafael, California, United States, 94903
      • Kaiser Permanente-San Rafael
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara
    • Santa Rosa, California, United States, 95403
      • Kaiser Permanente-Santa Rosa
    • Santa Rosa, California, United States, 95403
      • Sutter Pacific Medical Foundation
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente Cancer Treatment Center
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente-South San Francisco
    • Stockton, California, United States, 95210
      • Kaiser Permanente-Stockton
    • Vacaville, California, United States, 95688
      • Kaiser Permanente Medical Center-Vacaville
    • Vallejo, California, United States, 94589
      • Kaiser Permanente-Vallejo
    • Vallejo, California, United States, 94589
      • Sutter Solano Medical Center/Cancer Center
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente-Walnut Creek
    • Woodland Hills, California, United States, 91367
      • Kaiser Permanente-Woodland Hills
  • Colorado
    • Aurora, Colorado, United States, 80012
      • The Medical Center of Aurora
    • Boulder, Colorado, United States, 80301
      • Boulder Community Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente-Franklin
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80218
      • SCL Health Saint Joseph Hospital
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80222
      • Colorado Cancer Research Program NCORP
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
    • Grand Junction, Colorado, United States, 81501
      • Saint Mary's Hospital and Regional Medical Center
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Lafayette, Colorado, United States, 80026
      • Kaiser Permanente-Rock Creek
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Littleton, Colorado, United States, 80122
      • Littleton Adventist Hospital
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
    • Parker, Colorado, United States, 80138
      • Parker Adventist Hospital
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
    • Thornton, Colorado, United States, 80229
      • North Suburban Medical Center
    • Wheat Ridge, Colorado, United States, 80033
      • SCL Health Lutheran Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology and Oncology Associates
    • Stamford, Connecticut, United States, 06904
      • Stamford Hospital/Bennett Cancer Center
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Washington Hospital Center
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
    • Washington, District of Columbia, United States, 20016
      • Sibley Memorial Hospital
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Jupiter, Florida, United States, 33458
      • Jupiter Medical Center
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Orange Park, Florida, United States, 32073
      • 21st Century Oncology-Orange Park
    • Orlando, Florida, United States, 32803
      • Florida Hospital Orlando
    • Orlando, Florida, United States, 32806
      • UF Cancer Center at Orlando Health
    • Pensacola, Florida, United States, 32504
      • Sacred Heart Hospital
    • Weston, Florida, United States, 33331
      • Cleveland Clinic-Weston
  • Georgia
    • Albany, Georgia, United States, 31701
      • Phoebe Putney Memorial Hospital
    • Macon, Georgia, United States, 31201
      • Medical Center of Central Georgia
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96819
      • Kaiser Permanente Moanalua Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care Inc-POB II
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Oncology Inc-Kuakini
    • Kailua, Hawaii, United States, 96734
      • Castle Medical Center
    • Lihue, Hawaii, United States, 96766
      • Wilcox Memorial Hospital and Kauai Medical Clinic
    • Wailuku, Hawaii, United States, 96793
      • Maui Memorial Medical Center
    • Wailuku, Hawaii, United States, 96793
      • Pacific Cancer Institute of Maui
  • Idaho
    • Boise, Idaho, United States, 83712
      • Saint Luke's Mountain States Tumor Institute
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Mountain States Tumor Institute - Fruitland
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Mountain States Tumor Institute - Meridian
    • Nampa, Idaho, United States, 83686
      • Saint Luke's Mountain States Tumor Institute - Nampa
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Mountain States Tumor Institute-Twin Falls
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Bloomington, Illinois, United States, 61701
      • Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Canton, Illinois, United States, 61520
      • Graham Hospital Association
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
    • Chicago, Illinois, United States, 60631
      • Presence Resurrection Medical Center
    • Chicago, Illinois, United States, 60640
      • Weiss Memorial Hospital
    • Chicago, Illinois, United States, 60612
      • Jesse Brown Veterans Affairs Medical Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Heartland Cancer Research NCORP
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Eureka, Illinois, United States, 61530
      • Eureka Hospital
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Havana, Illinois, United States, 62644
      • Illinois CancerCare-Havana
    • Kankakee, Illinois, United States, 60901
      • Presence Saint Mary's Hospital
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • La Grange, Illinois, United States, 60525
      • AMITA Health Adventist Medical Center
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Monmouth, Illinois, United States, 61462
      • Illinois CancerCare-Monmouth
    • Monmouth, Illinois, United States, 61462
      • Holy Family Medical Center
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center Foundation
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Illinois CancerCare-Community Cancer Center
    • Oak Lawn, Illinois, United States, 60453-2699
      • Advocate Christ Medical Center
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Ottawa, Illinois, United States, 61350
      • Ottawa Regional Hospital and Healthcare Center
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Pekin, Illinois, United States, 61554
      • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Peru, Illinois, United States, 61354
      • Illinois Valley Hospital
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • River Forest, Illinois, United States, 60305
      • West Suburban Medical Center
    • Rockford, Illinois, United States, 61104
      • Swedish American Hospital
    • Spring Valley, Illinois, United States, 61362
      • Illinois CancerCare-Spring Valley
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • Franciscan Saint Francis Health-Beech Grove
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Elkhart, Indiana, United States, 46514
      • Michiana Hematology Oncology PC-Elkhart
    • Elkhart, Indiana, United States, 46514-2098
      • Elkhart Clinic
    • Fort Wayne, Indiana, United States, 46804
      • Radiation Oncology Associates PC
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology Inc-Parkview
    • Indianapolis, Indiana, United States, 46237
      • Franciscan Health Indianapolis
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Merrillville, Indiana, United States, 46410
      • Premier Oncology Hematology Associates
    • Mishawaka, Indiana, United States, 46545
      • Michiana Hematology Oncology PC-Mishawaka
    • Mishawaka, Indiana, United States, 46545
      • Saint Joseph Regional Medical Center-Mishawaka
    • Plymouth, Indiana, United States, 46563
      • Michiana Hematology Oncology PC-Plymouth
    • Richmond, Indiana, United States, 47374
      • Reid Health
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • Michiana Hematology Oncology PC-South Bend
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium
    • South Bend, Indiana, United States, 46617
      • South Bend Clinic
    • Westville, Indiana, United States, 46391
      • Michiana Hematology Oncology PC-Westville
  • Iowa
    • Bettendorf, Iowa, United States, 52722
      • University of Iowa Healthcare Cancer Services Quad Cities
    • Cedar Rapids, Iowa, United States, 52403
      • Mercy Hospital
    • Cedar Rapids, Iowa, United States, 52403
      • Oncology Associates at Mercy Medical Center
    • Cedar Rapids, Iowa, United States, 52402
      • Saint Luke's Hospital
    • Cedar Rapids, Iowa, United States, 52402
      • Physicians' Clinic of Iowa PC
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center-West Lakes
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50309
      • Iowa-Wide Oncology Research Coalition NCORP
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates-Laurel
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • Iowa City, Iowa, United States, 52246
      • Iowa City VA Healthcare System
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
    • Sioux City, Iowa, United States, 51104
      • Saint Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center-Sioux City
    • West Des Moines, Iowa, United States, 50266-7700
      • Methodist West Hospital
    • West Des Moines, Iowa, United States, 50266
      • Mercy Medical Center-West Lakes
  • Kansas
    • Kansas City, Kansas, United States, 66112
      • Providence Medical Center
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66213
      • Saint Luke's South Hospital
    • Prairie Village, Kansas, United States, 66208
      • Kansas City NCI Community Oncology Research Program
    • Shawnee Mission, Kansas, United States, 66204
      • Shawnee Mission Medical Center-KCCC
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Cancer Center / Stormont Vail Health
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center
    • Monroe, Louisiana, United States, 71202
      • University Health-Conway
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Science Center
    • Shreveport, Louisiana, United States, 71103
      • Louisiana State University Health Sciences Center Shreveport
    • Shreveport, Louisiana, United States, 71105
      • Highland Clinic
  • Maine
    • Augusta, Maine, United States, 04330
      • Harold Alfond Center for Cancer Care
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • MedStar Franklin Square Medical Center/Weinberg Cancer Institute
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Bethesda, Maryland, United States, 20889-5600
      • Walter Reed National Military Medical Center
    • Elkton, Maryland, United States, 21921
      • Union Hospital of Cecil County
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Brighton, Massachusetts, United States, 02135
      • Steward Saint Elizabeth's Medical Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
    • Pittsfield, Massachusetts, United States, 01201
      • Berkshire Hematology Oncology PC
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Bixby Medical Center
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Bay City, Michigan, United States, 48706
      • McLaren Cancer Institute-Bay City
    • Big Rapids, Michigan, United States, 49307
      • Spectrum Health Big Rapids Hospital
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Escanaba, Michigan, United States, 49829
      • Green Bay Oncology - Escanaba
    • Flint, Michigan, United States, 48532
      • McLaren Cancer Institute-Flint
    • Flint, Michigan, United States, 48532
      • Singh and Arora Hematology Oncology PC
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Grand Rapids, Michigan, United States, 49503
      • Cancer Research Consortium of West Michigan NCORP
    • Iron Mountain, Michigan, United States, 49801
      • Green Bay Oncology - Iron Mountain
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Medical Center
    • Lapeer, Michigan, United States, 48446
      • McLaren Cancer Institute-Lapeer Region
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital
    • Monroe, Michigan, United States, 48162
      • Toledo Clinic Cancer Centers-Monroe
    • Mount Clemens, Michigan, United States, 48043
      • McLaren Cancer Institute-Macomb
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Niles, Michigan, United States, 49120
      • Lakeland Hospital Niles
    • Petoskey, Michigan, United States, 49770
      • McLaren Cancer Institute-Northern Michigan
    • Reed City, Michigan, United States, 49677
      • Spectrum Health Reed City Hospital
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center Saint Joseph
    • Saint Joseph, Michigan, United States, 49085
      • Marie Yeager Cancer Center
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • Minnesota
    • Alexandria, Minnesota, United States, 56308
      • Medini, Eitan MD (UIA Investigator)
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview-Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis Veterans Medical Center
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center at Saint Cloud Hospital
    • Saint Cloud, Minnesota, United States, 56303
      • Saint Cloud Hospital
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro Minnesota Community Oncology Research Consortium
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center - Bolivar
    • Branson, Missouri, United States, 65616
      • Cox Cancer Center Branson
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Chesterfield, Missouri, United States, 63017
      • Saint Luke's Hospital
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel
    • Jefferson City, Missouri, United States, 65109
      • Capital Region Southwest Campus
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital Joplin
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Kansas City, Missouri, United States, 64108
      • Truman Medical Center
    • Kansas City, Missouri, United States, 64118
      • Heartland Hematology and Oncology Associates Incorporated
    • Kansas City, Missouri, United States, 64114
      • Saint Joseph Health Center
    • Lee's Summit, Missouri, United States, 64086
      • Saint Luke's East - Lee's Summit
    • Liberty, Missouri, United States, 64068
      • Liberty Radiation Oncology Center
    • Rolla, Missouri, United States, 65401
      • Delbert Day Cancer Institute at PCRMC
    • Rolla, Missouri, United States, 65401
      • Mercy Clinic-Rolla-Cancer and Hematology
    • Saint Joseph, Missouri, United States, 64507
      • Saint Joseph Oncology Inc
    • Saint Joseph, Missouri, United States, 64507
      • Heartland Regional Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63109
      • Saint Louis Cancer and Breast Institute-South City
    • Saint Louis, Missouri, United States, 63141
      • Saint Louis-Cape Girardeau CCOP
    • Saint Louis, Missouri, United States, 63141
      • Comprehensive Cancer Care PC
    • Springfield, Missouri, United States, 65804
      • Cancer Research for the Ozarks NCORP
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59102
      • Montana Cancer Consortium NCORP
    • Billings, Montana, United States, 59102
      • Saint Vincent Frontier Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Great Falls, Montana, United States, 59405
      • Big Sky Oncology
    • Havre, Montana, United States, 59501
      • Northern Montana Hospital
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59802
      • Montana Cancer Specialists
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • CHI Health Saint Francis
    • Kearney, Nebraska, United States, 68847
      • CHI Health Good Samaritan
    • North Platte, Nebraska, United States, 69101
      • Great Plains Health Callahan Cancer Center
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • Nevada Cancer Research Foundation CCOP
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • Voorhees, New Jersey, United States, 08043
      • Virtua Voorhees
  • New York
    • Buffalo, New York, United States, 14215
      • Veterans Affairs Western New York Health Care System-Buffalo
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of Central New York-East Syracuse
    • Glens Falls, New York, United States, 12801
      • Glens Falls Hospital
    • Middletown, New York, United States, 10940
      • Orange Regional Medical Center
    • New York, New York, United States, 10065
      • Weill Medical College of Cornell University
    • Staten Island, New York, United States, 10305
      • Staten Island University Hospital
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital Inc-Memorial Campus
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Concord, North Carolina, United States, 28025
      • Carolinas HealthCare System NorthEast
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
    • Kinston, North Carolina, United States, 28501
      • Vidant Oncology-Kinston
    • Washington, North Carolina, United States, 27889
      • Marion L Shepard Cancer Center at Vidant Beaufort Hospital
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic
    • Bismarck, North Dakota, United States, 58501
      • Saint Alexius Medical Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • Cleveland Clinic Akron General
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital/Cooper Cancer Center
    • Barberton, Ohio, United States, 44203
      • Summa Barberton Hospital
    • Bowling Green, Ohio, United States, 43402
      • Toledo Clinic Cancer Centers-Bowling Green
    • Canton, Ohio, United States, 44708
      • Mercy Medical Center
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati/Barrett Cancer Center
    • Clyde, Ohio, United States, 43410
      • North Coast Cancer Care-Clyde
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Health Center
    • Dayton, Ohio, United States, 45420
      • Dayton NCI Community Oncology Research Program
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Elyria, Ohio, United States, 44035
      • Mercy Cancer Center-Elyria
    • Elyria, Ohio, United States, 44035
      • Hematology Oncology Center Incorporated
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lima, Ohio, United States, 45801
      • Saint Rita's Medical Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Maumee, Ohio, United States, 43537
      • Toledo Clinic Cancer Centers-Maumee
    • Maumee, Ohio, United States, 43537
      • Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
    • Maumee, Ohio, United States, 43537
      • Saint Luke's Hospital
    • Norwalk, Ohio, United States, 44857
      • Fisher-Titus Medical Center
    • Oregon, Ohio, United States, 43616
      • Saint Charles Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic Cancer Centers-Oregon
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • Sylvania, Ohio, United States, 43560
      • ProMedica Flower Hospital
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43608
      • Saint Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Centers-Toledo
    • Toledo, Ohio, United States, 43614
      • University of Toledo
    • Toledo, Ohio, United States, 43617
      • Toledo Community Hospital Oncology Program CCOP
    • Toledo, Ohio, United States, 43606
      • The Toledo Hospital/Toledo Children's Hospital
    • Toledo, Ohio, United States, 43623
      • Mercy Saint Anne Hospital
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital
    • Wright-Patterson Air Force Base, Ohio, United States, 45433-5529
      • Wright-Patterson Medical Center
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
  • Oklahoma
    • Lawton, Oklahoma, United States, 73505
      • Cancer Centers of Southwest Oklahoma Research
    • Norman, Oklahoma, United States, 73071
      • Cancer Care Associates-Norman
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Hospital Oklahoma City
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Physicians of Oklahoma-Lakeside
  • Oregon
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Oregon City, Oregon, United States, 97045
      • Providence Willamette Falls Medical Center
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital and Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital and Health Center
    • Portland, Oregon, United States, 97216
      • Adventist Medical Center
    • Portland, Oregon, United States, 97227
      • Compass Oncology Rose Quarter
    • The Dalles, Oregon, United States, 97058
      • Mid-Columbia Medical Center/Celilo Cancer Center
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Butler, Pennsylvania, United States, 16001
      • Butler Memorial Hospital
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Ephrata, Pennsylvania, United States, 17522
      • Ephrata Cancer Center
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Lewistown, Pennsylvania, United States, 17044
      • Lewistown Hospital
    • Media, Pennsylvania, United States, 19063
      • Riddle Memorial Hospital
    • Paoli, Pennsylvania, United States, 19301
      • Paoli Memorial Hospital
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Medical Group PC-Robert Packer Hospital
    • Scranton, Pennsylvania, United States, 18508
      • Hematology and Oncology Associates of North East Pennsylvania
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • State College, Pennsylvania, United States, 16803
      • Mount Nittany Medical Center
    • Upland, Pennsylvania, United States, 19013
      • Associates In Hematology Oncology PC-Upland
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
    • Williamsport, Pennsylvania, United States, 17701
      • UPMC Susquehanna
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
    • Wynnewood, Pennsylvania, United States, 19096
      • Main Line Health NCORP
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Roper Hospital
    • Easley, South Carolina, United States, 29640
      • Greenville Health System Cancer Institute-Easley
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Faris
    • Greenville, South Carolina, United States, 29605
      • Greenville Memorial Hospital
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Institute-Eastside
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Butternut
    • Greenwood, South Carolina, United States, 29646
      • Self Regional Healthcare
    • Greer, South Carolina, United States, 29650
      • Greenville Health System Cancer Institute-Greer
    • Seneca, South Carolina, United States, 29672
      • Greenville Health System Cancer Institute-Seneca
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System Cancer Institute-Spartanburg
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57105
      • Avera McKennan Hospital and University Health Center
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Wellmont Holston Valley Hospital and Medical Center
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Center
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee - Knoxville
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Vermont
    • Berlin, Vermont, United States, 05602
      • Central Vermont Medical Center/National Life Cancer Treatment
    • Burlington, Vermont, United States, 05405
      • University of Vermont College of Medicine
    • White River Junction, Vermont, United States, 05009
      • White River Junction Veteran Administration Medical Center
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology Inc
    • Lynchburg, Virginia, United States, 24501
      • Centra Lynchburg Hematology-Oncology Clinic Inc
    • Norton, Virginia, United States, 24273
      • Southwest VA Regional Cancer Center
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
  • Washington
    • Centralia, Washington, United States, 98531
      • Providence Regional Cancer System-Centralia
    • Federal Way, Washington, United States, 98003
      • Saint Francis Hospital
    • Lakewood, Washington, United States, 98499
      • Saint Clare Hospital
    • Olympia, Washington, United States, 98506-5166
      • Providence - Saint Peter Hospital
    • Puyallup, Washington, United States, 98372
      • MultiCare Good Samaritan Hospital
    • Spokane, Washington, United States, 99220
      • Rockwood Clinic
    • Tacoma, Washington, United States, 98405
      • MultiCare Tacoma General Hospital
    • Tacoma, Washington, United States, 98405
      • MultiCare Allenmore Hospital
    • Tacoma, Washington, United States, 98405
      • Northwest NCI Community Oncology Research Program
    • Tacoma, Washington, United States, 98405
      • Saint Joseph Medical Center
    • Vancouver, Washington, United States, 98686
      • Legacy Salmon Creek Hospital
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
    • Vancouver, Washington, United States, 98684
      • Compass Oncology Vancouver
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Charleston Division
    • Huntington, West Virginia, United States, 25701
      • Edwards Comprehensive Cancer Center
  • Wisconsin
    • Antigo, Wisconsin, United States, 54409
      • Langlade Hospital and Cancer Center
    • Appleton, Wisconsin, United States, 54913
      • Fox Valley Hematology and Oncology SC-Appleton
    • Burlington, Wisconsin, United States, 53105
      • Aurora Cancer Care-Southern Lakes VLCC
    • Chippewa Falls, Wisconsin, United States, 54729
      • Marshfield Clinic-Chippewa Center
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Clinic Cancer Center at Sacred Heart
    • Franklin, Wisconsin, United States, 53132
      • Aurora Cancer Care-Franklin
    • Germantown, Wisconsin, United States, 53022
      • Aurora Health Care Germantown Health Center
    • Glendale, Wisconsin, United States, 53212
      • Aurora Cancer Care-Glendale
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Green Bay, Wisconsin, United States, 54303
      • Saint Vincent Hospital Cancer Center at Saint Mary's
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology Limited at Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology at Saint Vincent Hospital
    • Kenosha, Wisconsin, United States, 53142
      • Aurora Cancer Care-Kenosha South
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Manitowoc, Wisconsin, United States, 54221
      • Holy Family Memorial Hospital
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic-Minocqua Center
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology - Oconto Falls
    • Racine, Wisconsin, United States, 53406
      • Aurora Cancer Care-Racine
    • Rhinelander, Wisconsin, United States, 54501
      • Ascension Saint Mary's Hospital
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Clinic-Rice Lake Center
    • Sheboygan, Wisconsin, United States, 53081
      • HSHS Saint Nicholas Hospital
    • Stevens Point, Wisconsin, United States, 54481
      • Ascension Saint Michael's Hospital
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology - Sturgeon Bay
    • Waukesha, Wisconsin, United States, 53188
      • Aurora Cancer Care-Waukesha
    • Wausau, Wisconsin, United States, 54401
      • Aspirus Regional Cancer Center
    • Wauwatosa, Wisconsin, United States, 53226
      • Aurora Cancer Care-Milwaukee West
    • Weston, Wisconsin, United States, 54476
      • Diagnostic and Treatment Center
    • Weston, Wisconsin, United States, 54476
      • Marshfield Clinic - Weston Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Marshfield Clinic - Wisconsin Rapids Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Aspirus UW Cancer Center
  • Wyoming
    • Casper, Wyoming, United States, 82609
      • Rocky Mountain Oncology
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Renal cell carcinoma with some component of clear cell histology
• Metastatic or unresectable disease
• Must have been treated with at least 1 prior VEGFR tyrosine kinase inhibitor treatment and have progressed or have been intolerant to treatment
• No prior systemic therapy with a vascular endothelial growth factor (VEGF) binding agent (e.g., bevacizumab)
• No prior systemic therapy with any mechanistic target of rapamycin (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus)
• Prior cytokine therapy is allowed
• Any systemic therapy must be completed at least 4 weeks prior to registration
• >= 2 weeks since any prior radiation (including palliative)

• Patients must not have had a major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to study registration, and must have fully recovered from any such procedure

  • The following are not considered to be major procedures: thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies and routine dental procedures
• Patients must have measurable disease by RECIST criteria; lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan

• No active brain metastases: patients with treated, stable brain metastases for at least three months are eligible as long as they meet the following criteria:

  • Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or CT) (stable dose of anticonvulsants are allowed); treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator [LINAC], or equivalent) or a combination as deemed appropriate by the treating physician; patients with central nervous system (CNS) metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 are not eligible
  • Baseline brain imaging (MRI/CT) is required
• No serious non-healing wound, ulcer, or bone fracture

• No arterial thrombotic events within 6 months of registration:

  • Including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block), significant vascular disease (i.e., aortic aneurysm, history of aortic dissection), or any other arterial thrombotic event are ineligible
• Patients who have experienced a deep venous thrombosis or pulmonary embolus within the past 6 months must be on stable therapeutic anticoagulation to be enrolled to this study
• Patients receiving anti-platelet agents and prophylactic anticoagulation are eligible
• No inadequately controlled hypertension: (defined as a blood pressure of >= 160 mmHg systolic and/or >= 90 mmHg diastolic on medication), or any prior history of hypertensive crisis or hypertensive encephalopathy

• No known severe impairment of lung function, defined as >= grade 2 dyspnea or cough, or either:

  • Requirement of supplemental oxygen, or
  • In cases where pulmonary function or pulse oximetry tests have been obtained, forced expiratory volume of the lung in one second (FEV1) or forced vital capacity (FVC) are < 50% of predicted, or single breath diffusing capacity of the lung for carbon monoxide (DLCO) is < 35% of predicted or resting room oxygen saturation is less than 90%
• No active or severe liver disease (e.g. acute or chronic hepatitis, cirrhosis)
• No positive serology for anti-hemoglobin C (HBC) or anti-hepatitis C virus (HCV) antibodies; hepatitis B virus (HBV) seropositive patients (hepatitis B surface antigen [HBsAg] positive) are eligible if they are closely monitored for evidence of active HBV infection by HBV deoxryribonucleic acid (DNA) testing and agree to receive suppressive therapy with lamivudine or other HBV-suppressive therapy until at least 4 weeks after the last dose of everolimus
• No New York Heart Association (NYHA) class >= 2 congestive heart failure
• No active bleeding or chronic hemorrhagic diathesis or increased risk for bleeding: Including but not limited to history of major bleeding within 6 months (e.g. gastrointestinal, lung, CNS sites; or required transfusion support)
• No history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to the initiation of treatment
• No ongoing immunosuppressive therapy: including chronic systemic treatment with corticosteroids (>= 10 mg/day prednisone equivalent)
• Archival tissue must be available for submission: though it is optional patients to choose to participate in the correlative substudies or not

• Patients who are pregnant or nursing are not eligible

  • Women of child bearing potential must have a negative serum or urine pregnancy test within 16 days prior to registration

  • Women of child-bearing potential include:

    • Any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >= 12 consecutive months)
    • Women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35m IU/mL
    • Women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy)
• Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 or Karnofsky score >= 60%
• Granulocytes >= 1,500/μL
• Platelet count >= 100,000/μL
• Calculated creatinine clearance >= 30 mL/minute (modified Cockroft and Gault formula)
• Bilirubin =< 1.5 x upper limits of normal
• Aspartate aminotransferase (AST) =< 2.5 x upper limits of normal (ULN)
• Fasting serum triglycerides =< 200 mg/dL
• Serum cholesterol =< 300 mg/dL
• Fasting serum glucose =< 1.5 x ULN
• Urine protein to creatinine ratio < 1.0 or urine protein =< 1+

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (everolimus); Patients receive everolimus PO QD on days 1-28.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Drug: Everolimus; Given PO; Other Names: 42-O-(2-Hydroxy)ethyl Rapamycin; Afinitor; Certican; RAD 001; RAD001; Votubia; Zortress
Experimental: Arm II (everolimus with bevacizumab); Patients receive everolimus PO QD on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 15.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Drug: Everolimus; Given PO; Other Names: 42-O-(2-Hydroxy)ethyl Rapamycin; Afinitor; Certican; RAD 001; RAD001; Votubia; Zortress; Biological: Bevacizumab; Given IV; Other Names: Avastin; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; Bevacizumab Biosimilar BEVZ92; Bevacizumab Biosimilar BI 695502; Bevacizumab Biosimilar CBT 124; Bevacizumab Biosimilar FKB238; Bevacizumab Biosimilar MIL60; Bevacizumab Biosimilar QL 1101; Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer; Recombinant Humanized Anti-VEGF Monoclonal Antibody; rhuMab-VEGF; BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.	The time from date of randomization to date of death due to any cause, assessed up to 5.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.	The time from randomization to disease progression or death from any cause, assessed up to 5.5 years
Objective Response Rate (CR + PR)	The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients.	Up to 5.5 years
Toxicities, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0	The number of patients reporting grade 3 or higher adverse events as graded by the NCI's Common Toxicity Criteria (CTCAE) Version 4 are reported here. A complete list of all reported adverse events is reported in the Adverse Events section of this report.	Up to 30 days after completion of study treatment

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: George Philips, Alliance for Clinical Trials in Oncology

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2010
• Primary Completion (Actual): December 15, 2017
• Study Completion (Actual): December 16, 2017

Study Registration Dates

• First Submitted: September 8, 2010
• First Submitted That Met QC Criteria: September 8, 2010
• First Posted (Estimate): September 9, 2010

Study Record Updates

• Last Update Posted (Actual): March 6, 2019
• Last Update Submitted That Met QC Criteria: March 5, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibodies; Immunoglobulins; Bevacizumab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Everolimus; Immunoglobulin G; Endothelial Growth Factors
• Other Study ID Numbers: NCI-2011-02603 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180821 (U.S. NIH Grant/Contract); U10CA031946 (U.S. NIH Grant/Contract); CDR0000684313; CALGB 90802 (Other Identifier: Alliance for Clinical Trials in Oncology); CALGB-90802 (Other Identifier: CTEP)