Bevacizumab, Sorafenib Tosylate, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer

The BeST Trial: A Randomized Phase II Study of VEGF, RAF Kinase, and mTOR Combination Targeted Therapy (CTT) With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma

This randomized phase II trial studies different combinations of bevacizumab, temsirolimus, and sorafenib tosylate to see how well they work compared with bevacizumab alone in treating patients with kidney cancer that has spread to other places in the body. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab and sorafenib tosylate may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving different combinations of bevacizumab, sorafenib tosylate, and temsirolimus may be more effective than bevacizumab alone in treating metastatic kidney cancer.

Study Overview

• Status: Completed
• Conditions: Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Renal Cell Cancer AJCC v7
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Bevacizumab; Drug: Temsirolimus; Drug: Sorafenib Tosylate

Detailed Description

PRIMARY OBJECTIVES:

I. To assess progression-free survival on each arm of combination targeted therapy (CTT) compared to that of bevacizumab alone.

SECONDARY OBJECTIVES:

I. To assess the significance of changes in tumor size over early time points as a predictor of progression-free survival (PFS).

II. To quantify the number and percent of patients who have stable disease at 6 months of therapy (failure to progress) in each treatment arm of CTT in patients with metastatic renal cell carcinoma (RCC).

III. To evaluate the safety of each treatment arm of combination targeted therapy (CTT) in patients with metastatic RCC.

IV. To assess overall survival in each arm of the study. V. To assess the objective response rate in each treatment arm of CTT in patients with metastatic RCC.

VI. To assess pathology, angiogenesis histology and to assess activation status of mitogen activated protein (MAP) kinase and vascular endothelial growth factor receptor 2 (VEGFR2) pathways and relate to clinical outcome.

TERTIARY OBJECTIVES:

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

II. To relate changes in tumor perfusion and vascular permeability on serial dynamic contrast-enhanced magnetic resonance imaging (MRI) to clinical outcome and radiologic regression detected by other standard methods.

III. To assess the potential of dynamic contrast-enhanced (DCE)-MRI imaging as a biomarker for response to therapy and/or as a prognostic indicator of disease progression.

IV. To assess site readiness and ability in acquiring DCE-MRI data. V. To determine the relationship between tumor and blood biomarkers and clinical outcomes of patients treated with the combination of targeted agents.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM A: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.

ARM B: Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A.

ARM C: Patients receive bevacizumab as in Arm A and sorafenib tosylate orally (PO) twice daily (BID) on days 1-5, 8-12, 15-19, and 22-26.

ARM D: Patients receive sorafenib tosylate PO BID on days 1-28 and temsirolimus as in Arm B.

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

After completion of study treatment, patients are followed up periodically for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 361
• Phase: Phase 2

Contacts and Locations

Study Locations

• Peru
  • Lima, Peru, Lima 34
    • Instituto Nacional de Enfermedades Neoplasicas
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
    • Mobile, Alabama, United States, 36608
      • Providence Hospital
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
    • Tucson, Arizona, United States, 85724
      • The University of Arizona Medical Center-University Campus
  • Arkansas
    • Fort Smith, Arkansas, United States, 72903
      • Mercy Hospital Fort Smith
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Memorial Hospital
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center-Herrick Campus
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Burlingame, California, United States, 94010
      • Mills-Peninsula Medical Center
    • Castro Valley, California, United States, 94546
      • Eden Hospital 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
    • Fremont, California, United States, 94538
      • Valley Medical Oncology Consultants-Fremont
    • Glendale, California, United States, 91204
      • Glendale Memorial Hospital and Health Center
    • Greenbrae, California, United States, 94904
      • Marin Cancer Care Inc
    • Greenbrae, California, United States, 94904
      • Marin General Hospital
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Marysville, California, United States, 95901
      • Fremont - Rideout Cancer Center
    • Mountain View, California, United States, 94040
      • El Camino Hospital
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Camino Division
    • Novato, California, United States, 94945
      • Sutter Cancer Research Consortium
    • 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
    • Orange, California, United States, 92868
      • Saint Joseph Hospital - Orange
    • Palo Alto, California, United States, 94301
      • Palo Alto Medical Foundation Health Care
    • Pleasanton, California, United States, 94588
      • Valley Care Health System - Pleasanton
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • San Diego, California, United States, 92103
      • University of California San Diego
    • San Diego, California, United States, 92161
      • Veterans Administration-San Diego Medical Center
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center-Pacific Campus
    • San Pablo, California, United States, 94806
      • Doctors Medical Center- JC Robinson Regional Cancer Center
    • Truckee, California, United States, 96161
      • Gene Upshaw Memorial Tahoe Forest Cancer Center
    • Vallejo, California, United States, 94589
      • Sutter Solano Medical Center/Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • 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
    • Colorado Springs, Colorado, United States, 80909
      • UCHealth Memorial Hospital Central
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Denver, Colorado, United States, 80217-3364
      • University of Colorado
    • 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
    • Edwards, Colorado, United States, 81632
      • The Shaw Regional Cancer Center
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
    • Glenwood Springs, Colorado, United States, 81601
      • Valley View Hospital Cancer Center
    • Grand Junction, Colorado, United States, 81501
      • Saint Mary's Hospital and Regional Medical Center
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony 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
    • Montrose, Colorado, United States, 81401
      • Montrose Memorial 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
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Orlando, Florida, United States, 32806
      • UF Cancer Center at Orlando Health
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B Amos Cancer Center
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center-Gainesville
    • Macon, Georgia, United States, 31201
      • Medical Center of Central Georgia
  • Idaho
    • Post Falls, Idaho, United States, 83854
      • Kootenai Cancer Center
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Health
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Berwyn, Illinois, United States, 60402
      • MacNeal Hospital and Cancer Center
    • 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, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60611
      • Hematology and Oncology Associates
    • Chicago, Illinois, United States, 60631
      • Presence Resurrection Medical Center
    • 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
    • Elgin, Illinois, United States, 60123
      • Advocate Sherman Hospital
    • Elk Grove Village, Illinois, United States, 60007
      • AMITA Health Alexian Brothers Medical Center
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Eureka, Illinois, United States, 61530
      • Eureka Hospital
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Cottage
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Havana, Illinois, United States, 62644
      • Illinois CancerCare-Havana
    • Highland Park, Illinois, United States, 60035
      • Hematology Oncology Associates of Illinois-Highland Park
    • Hopedale, Illinois, United States, 61747
      • Hopedale Medical Complex - Hospital
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates Limited
    • Joliet, Illinois, United States, 60432
      • Midwest Center for Hematology Oncology
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Kewanee, Illinois, United States, 61443
      • Kewanee Hospital
    • La Grange, Illinois, United States, 60525
      • AMITA Health Adventist Medical Center
    • Libertyville, Illinois, United States, 60048
      • NorthShore Hematology Oncology-Libertyville
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Moline, Illinois, United States, 61265
      • Garneau, Stewart C MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Porubcin, Michael MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Spector, David MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Trinity Medical Center
    • Moline, Illinois, United States, 61265
      • Sharis, Christine M MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Stoffel, Thomas J MD (UIA Investigator)
    • 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
    • Naperville, Illinois, United States, 60563
      • DuPage Medical Group-Ogden
    • Naperville, Illinois, United States, 60540
      • AMG Oncology - Naperville
    • Niles, Illinois, United States, 60714
      • Illinois Cancer Specialists-Niles
    • 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
    • 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
    • Pekin, Illinois, United States, 61554
      • Pekin Hospital
    • 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
    • Rockford, Illinois, United States, 61114
      • SwedishAmerican Regional Cancer Center/ACT
    • Rockford, Illinois, United States, 61104
      • Swedish American Hospital
    • Skokie, Illinois, United States, 60076
      • Hematology Oncology Associates of Illinois - Skokie
    • Spring Valley, Illinois, United States, 61362
      • Saint Margaret's 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, 46845
      • Fort Wayne Medical Oncology and Hematology Inc-Parkview
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Sidney and Lois Eskenazi Hospital
    • Indianapolis, Indiana, United States, 46202
      • Richard L. Roudebush Veterans Affairs Medical Center
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Research LLC
    • Michigan City, Indiana, United States, 46360
      • Franciscan Saint Anthony Health-Michigan City
    • 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
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC - Ames
    • Bettendorf, Iowa, United States, 52722
      • Constantinou, Costas L MD (UIA Investigator)
    • 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
    • Davenport, Iowa, United States, 52803
      • Genesis Medical Center - East Campus
    • Davenport, Iowa, United States, 52804
      • Genesis Medical Center - West Campus
    • 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
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • Mason City, Iowa, United States, 50401
      • Mercy Medical Center - North Iowa
    • Ottumwa, Iowa, United States, 52501
      • Ottumwa Regional Health Center
    • 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
  • Kansas
    • Anthony, Kansas, United States, 67003
      • Hospital District Sixth of Harper County
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66213
      • Saint Luke's South Hospital
    • Overland Park, Kansas, United States, 66210
      • Radiation Oncology Practice Corporation Southwest
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Shawnee Mission, Kansas, United States, 66204
      • Shawnee Mission Medical Center-KCCC
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Cancer Center / Stormont Vail Health
    • Topeka, Kansas, United States, 66606
      • Saint Francis Hospital and Medical Center - Topeka
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Wichita NCI Community Oncology Research Program
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Kentucky
    • Louisville, Kentucky, United States, 40215
      • Doctors Carrol, Sheth, Raghavan
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center
    • Baton Rouge, Louisiana, United States, 70809
      • Ochsner Health Center-Summa
    • Baton Rouge, Louisiana, United States, 70806
      • Baton Rouge General Medical Center
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Science Center
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
    • Lewiston, Maine, United States, 04240
      • Saint Mary's Regional Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Elkton, Maryland, United States, 21921
      • Union Hospital of Cecil County
    • Frederick, Maryland, United States, 21701
      • Frederick Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Bixby Medical Center
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium NCORP
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Big Rapids, Michigan, United States, 49307
      • Spectrum Health Big Rapids Hospital
    • Dearborn, Michigan, United States, 48124
      • Beaumont Hospital-Dearborn
    • Detroit, Michigan, United States, 48236
      • Ascension Saint John Hospital
    • Escanaba, Michigan, United States, 49829
      • Green Bay Oncology - Escanaba
    • Flint, Michigan, United States, 48532
      • Genesys Regional Medical Center-West Flint Campus
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • 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
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • 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
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital
    • Monroe, Michigan, United States, 48162
      • Toledo Clinic Cancer Centers-Monroe
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Muskegon, Michigan, United States, 49442
      • Mercy Health Partners-Hackley Campus
    • Niles, Michigan, United States, 49120
      • Lakeland Hospital Niles
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Lake Huron Medical Center
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center Saint Joseph
    • Saint Joseph, Michigan, United States, 49085
      • Marie Yeager Cancer Center
    • Saint Joseph, Michigan, United States, 49085
      • Oncology Care Associates PLLC
    • Southfield, Michigan, United States, 48075
      • Providence Hospital-Southfield Cancer Center
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
    • 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
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Cancer Center
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Saint Mary's Medical Center
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview-Southdale Hospital
    • Fergus Falls, Minnesota, United States, 56537
      • Etzell, Paul S MD (UIA Investigator)
    • Fergus Falls, Minnesota, United States, 56537
      • Swenson, Wade II, MD (UIA Investigator)
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Litchfield, Minnesota, United States, 55355
      • Meeker County Memorial Hospital
    • 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, 55407
      • Virginia Piper Cancer Institute
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • 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
    • Saint Paul, Minnesota, United States, 55102
      • Saint Joseph's Hospital - Healtheast
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • 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
    • Woodbury, Minnesota, United States, 55125
      • Woodwinds Health Campus
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
    • Pascagoula, Mississippi, United States, 39581
      • Singing River Hospital
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Hospital
    • Independence, Missouri, United States, 64057
      • Centerpoint Medical Center LLC
    • 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
    • Kansas City, Missouri, United States, 64114
      • Radiation Oncology Practice Corporation South
    • Kansas City, Missouri, United States, 64154
      • Radiation Oncology Practice Corporation - North
    • Lee's Summit, Missouri, United States, 64086
      • Saint Luke's East - Lee's Summit
    • Liberty, Missouri, United States, 64068
      • Liberty Radiation Oncology Center
    • 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, 63110
      • Saint Louis University Hospital
    • 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
      • Center for Cancer Care and Research
    • 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, 59101
      • Northern Rockies Radiation Oncology Center
    • 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
      • Berdeaux, Donald MD (UIA Investigator)
    • 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, 59804
      • Community Medical Hospital
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • 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 Hampshire
    • Portsmouth, New Hampshire, United States, 03802
      • Portsmouth Regional Hospital
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • East Orange, New Jersey, United States, 07018-1095
      • Veterans Adminstration New Jersey Health Care System
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • Newark, New Jersey, United States, 07101
      • Rutgers New Jersey Medical School
    • Summit, New Jersey, United States, 07902
      • Overlook Hospital
    • Vineland, New Jersey, United States, 08360
      • Inspira Medical Center Vineland
    • Voorhees, New Jersey, United States, 08043
      • Virtua Voorhees
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Campus
    • Bronx, New York, United States, 10466
      • Montefiore Medical Center-Wakefield Campus
    • Brooklyn, New York, United States, 11203
      • Kings County Hospital
    • Brooklyn, New York, United States, 11203
      • State University of New York Downstate Medical Center
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Cooperstown, New York, United States, 13326
      • Mary Imogene Bassett Hospital
    • 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
    • Lake Success, New York, United States, 11042
      • Northwell Health NCORP
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • Middletown, New York, United States, 10940
      • Orange Regional Medical Center
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center
    • New York, New York, United States, 10032
      • Columbia University/Herbert Irving Cancer Center
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital Inc-Memorial Campus
    • Burlington, North Carolina, United States, 27215
      • Cone Health Cancer Center at Alamance Regional
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center-Goldsboro
    • 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
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth of the Carolinas-Moore Regional Hospital
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
    • Winston-Salem, North Carolina, United States, 27104
      • Southeast Clinical Oncology Research (SCOR) Consortium NCORP
  • 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
    • Bellefontaine, Ohio, United States, 43311
      • Mary Rutan Hospital
    • Bowling Green, Ohio, United States, 43402
      • Toledo Clinic Cancer Centers-Bowling Green
    • Canton, Ohio, United States, 44710
      • Aultman Health Foundation
    • Canton, Ohio, United States, 44708
      • Mercy Medical Center
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Clyde, Ohio, United States, 43410
      • North Coast Cancer Care-Clyde
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Columbus, Ohio, United States, 43215
      • Columbus NCI Community Oncology Research Program
    • 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
    • Dayton, Ohio, United States, 45428
      • Veteran Affairs Medical Center
    • Delaware, Ohio, United States, 43015
      • Grady Memorial 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
    • Fremont, Ohio, United States, 43420
      • Fremont Memorial Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lima, Ohio, United States, 45801
      • Saint Rita's Medical Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Marietta, Ohio, United States, 45750
      • Marietta 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
    • Mount Vernon, Ohio, United States, 43050
      • Knox Community Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial 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
    • Sandusky, Ohio, United States, 44870
      • Firelands Regional Medical Center
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • 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
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System Cancer Care Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at Saint Francis
  • Oregon
    • Coos Bay, Oregon, United States, 97420
      • Bay Area Hospital
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Bethlehem, Pennsylvania, United States, 18015
      • Saint Luke's University Hospital-Bethlehem Campus
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • Lancaster, Pennsylvania, United States, 17604
      • Lancaster General Hospital
    • Lemoyne, Pennsylvania, United States, 17043
      • Central PA Hematology-Medical Oncology Associates PC
    • Media, Pennsylvania, United States, 19063
      • Riddle Memorial Hospital
    • Paoli, Pennsylvania, United States, 19301
      • Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Medical Center Philadelphia
    • Philadelphia, Pennsylvania, United States, 19107
      • Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
    • Scranton, Pennsylvania, United States, 18510
      • Scranton Hematology Oncology
    • Scranton, Pennsylvania, United States, 18501
      • Mercy Hospital
    • Scranton, Pennsylvania, United States, 18508
      • Hematology and Oncology Associates of North East Pennsylvania
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
    • Wilkes-Barre, Pennsylvania, United States, 18765
      • Geisinger South Wilkes-Barre
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Memorial Hospital of Rhode Island
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Hospital
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center Oncology Clinic
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center
    • Sioux Falls, South Dakota, United States, 57105
      • Avera McKennan Hospital and University Health Center
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Vanderbilt-Ingram Cancer Center Cool Springs
    • Jackson, Tennessee, United States, 38301
      • Jackson-Madison County General Hospital
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Center
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee - Knoxville
    • Knoxville, Tennessee, United States, 37909
      • Tennessee Cancer Specialists-Dowell Springs
    • Knoxville, Tennessee, United States, 37920
      • East Tennessee Baptist Hospital-Mercy Health Partners
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee Health Science Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
  • Texas
    • Amarillo, Texas, United States, 79106
      • The Don and Sybil Harrington Cancer Center
    • Austin, Texas, United States, 78705
      • Texas Oncology-Austin Midtown
    • Austin, Texas, United States, 78731
      • Texas Oncology - Central Austin Cancer Center
    • Austin, Texas, United States, 78745
      • Texas Oncology - South Austin Cancer Center
    • Austin, Texas, United States, 78758
      • Texas Oncology-Austin North
    • Austin, Texas, United States, 78759
      • Texas Oncology Seton Northwest
    • Burleson, Texas, United States, 76115
      • The Center for Cancer and Blood Disorders-Burleson
    • Cedar Park, Texas, United States, 78613
      • Texas Oncology-Cedar Park
    • Cleburne, Texas, United States, 76033
      • The Center for Cancer and Blood Disorders-Cleburne
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders-Fort Worth
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
    • Houston, Texas, United States, 77030
      • Michael E DeBakey VA Medical Center
    • Houston, Texas, United States, 77030
      • The Methodist Hospital System
    • Houston, Texas, United States, 77030
      • Ben Taub General Hospital
    • Houston, Texas, United States, 77030
      • Baylor Saint Luke's Medical Center
    • Mineral Wells, Texas, United States, 76067
      • The Center for Cancer and Blood Disorders-Mineral Wells
    • Round Rock, Texas, United States, 78665
      • Texas Oncology-Seton Williamson
    • Round Rock, Texas, United States, 78681
      • Texas Oncology - Round Rock Cancer Center
    • San Marcos, Texas, United States, 78666
      • Texas Oncology- San Marcos
    • Weatherford, Texas, United States, 76086
      • The Center for Cancer and Blood Disorders-Weatherford
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology Inc
    • Martinsville, Virginia, United States, 24115
      • Sovah Health Martinsville
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
  • Washington
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98112
      • Kaiser Permanente Washington
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology PS
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99220
      • Rockwood Clinic
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Charleston Division
  • Wisconsin
    • Appleton, Wisconsin, United States, 54913
      • Fox Valley Hematology and Oncology SC-Appleton
    • Chippewa Falls, Wisconsin, United States, 54729
      • Marshfield Clinic-Chippewa Center
    • Eau Claire, Wisconsin, United States, 54701
      • HSHS Sacred Heart Hospital
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Clinic Cancer Center at Sacred Heart
    • 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
    • Johnson Creek, Wisconsin, United States, 53038
      • UW Cancer Center Johnson Creek
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Madison, Wisconsin, United States, 53717
      • Dean Hematology and Oncology Clinic
    • Madison, Wisconsin, United States, 53715
      • UW Health Oncology-One South Park
    • 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
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic-Minocqua Center
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology - Oconto Falls
    • Rhinelander, Wisconsin, United States, 54501
      • Ascension Saint Mary's Hospital
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Clinic-Rice Lake Center
    • Stevens Point, Wisconsin, United States, 54481
      • Saint Michael's Hospital
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology - Sturgeon Bay
    • Wausau, Wisconsin, United States, 54401
      • Marshfield Clinic-Wausau Center
    • 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:

• Patients will be required to have the clear cell variant of renal cell carcinoma with less than 25% of any other histology (including, but not limited to, papillary or chromophobe or oncocytic); there must be histologic confirmation by treating center of either primary or metastatic lesion
• Patients will be required to have measurable metastatic disease that is not curable by standard radiation therapy or surgery; all sites must be assessed within 4 weeks prior to study entry

• Previous nephrectomy is required with the following exceptions:

  • Primary tumor =< 5 cm, or
  • Extensive liver (> 30% of liver parenchymal) or multiple (> 5) bone metastases, making nephrectomy a clinically questionable procedure
  • Unresectable primary tumor due to invasion into adjacent organs or encasing the aorta or vena cava
• No prior cytotoxic chemotherapy; a maximum of one prior regimen of either vaccine or cytokine-based immunotherapy disease is permitted
• No prior anti-angiogenic therapy including, but not limited to, SU11248, ZD6474 or VEGF Trap; no prior therapy with bevacizumab, mammalian target of rapamycin (mTOR) inhibitors (including, but not limited to, temsirolimus), or sorafenib will be allowed; thalidomide or interferon alpha (IFNalpha) are allowed either for adjuvant therapy or stage IV disease
• No immunotherapy within 4 weeks of randomization; toxicities from immunotherapy must have resolved and a minimum of two weeks must pass prior to enrollment
• Prior radiation therapy is permitted, but toxicities from radiation must have resolved and a minimum of 2 weeks must pass prior to randomization
• No history or clinical evidence of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastasis, or history of stroke within the past 48 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of greater than 12 weeks
• Hemoglobin (Hgb) >= 9.0 g/dL (transfusions allowed prior to enrollment)
• White blood count (WBC) >= 3,000/mm^3
• Absolute granulocyte count (AGC) >= 1,200/mm^3
• Platelet count >= 100,000/mm^3
• Serum creatinine =< 1.5 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) >= 55 ml/min
• Total bilirubin =< 1.5 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (or =< 5.0 x ULN in the presence of liver metastases)
• International normalized ratio (INR) =< 1.5
• Activated partial thromboplastin time (aPTT) within normal limits
• Fasting cholesterol < 350 mg/dL (9.0 mmol/L)
• Fasting triglycerides < 400 mg/dL (4.56 mmol/L)
• Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease-free for >= 5 years prior to the time of randomization
• No history of allergic reactions attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biologic composition to sorafenib, temsirolimus or bevacizumab
• No history of bleeding diathesis or coagulopathy
• Any condition that impairs patient's ability to swallow pills will make patient ineligible
• No major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization
• No anticipated need for major surgery during the course of the study
• No current or recent (within 4 weeks of enrollment) use of full-dose of anticoagulants or thrombolytic agents (except as required to maintain patency of preexisting or permanent indwelling IV catheters, for those patients receiving warfarin, INR must be =< 1.5)

• No clinically significant cardiovascular disease, defined as one of the following:

  • Patients with uncontrolled hypertension (blood pressure > 150/100 mm/Hg at the time of enrollment); patients with hypertension and blood pressure =< 150/100 mm/Hg on stable antihypertensive regimen are eligible
  • Myocardial infarction or unstable angina < 24 weeks prior to registration
  • New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris
  • Grade II or greater peripheral vascular disease
• No serious, non-healing wound, ulcer, or bone fracture

• No significant proteinuria at baseline; urine protein must be screened within 2 weeks prior to randomization by urine analysis for urine protein creatinine (UPC) ratio; if UPC ratio is > 0.5, 24-hour urine protein is to be obtained and the level must be < 1000 mg for patient enrollment

  • NOTE: UPC ratio of spot urine is an estimation of the 24 urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
• No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on day 0 or psychiatric illness/social situations that would limit compliance with study requirements

• Patients currently taking any of the following cytochrome P450 enzyme-inducing drugs are ineligible:

  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • Rifampin
• Pregnant and breastfeeding women are excluded from the study; breastfeeding should be discontinued while receiving therapy; patients must have pregnancy test within 7 days prior to patient randomization if woman is of child-bearing capacity
• Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (bevacizumab); Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; 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
Experimental: Arm B (bevacizumab and temsirolimus); Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; 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; Drug: Temsirolimus; Given IV; Other Names: Torisel; CCI-779; CCI-779 Rapamycin Analog; Cell Cycle Inhibitor 779; Rapamycin Analog; Rapamycin Analog CCI-779
Experimental: Arm C (bevacizumab and sorafenib tosylate); Patients receive bevacizumab as in Arm A and sorafenib tosylate PO BID on days 1-5, 8-12, 15-19, and 22-26.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; 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; Drug: Sorafenib Tosylate; Given PO; Other Names: BAY 54-9085; Nexavar; BAY 43-9006 Tosylate; sorafenib
Experimental: Arm D (sorafenib tosylate and temsirolimus); Patients receive sorafenib tosylate PO BID on days 1-28 and temsirolimus as in Arm B.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Drug: Temsirolimus; Given IV; Other Names: Torisel; CCI-779; CCI-779 Rapamycin Analog; Cell Cycle Inhibitor 779; Rapamycin Analog; Rapamycin Analog CCI-779; Drug: Sorafenib Tosylate; Given PO; Other Names: BAY 54-9085; Nexavar; BAY 43-9006 Tosylate; sorafenib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Progression-free survival is defined as time from randomization to clinical evidence of disease progression or death from any cause without progression. Patients alive without progression were censored at the date of last disease assessment.	Assessed every 2 cycles for the first 12 cycles, then every 3 cycles until treatment discontinuation, then every 8 weeks until disease progression or up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With Stable Disease at 6 Months	Patients whose date of progression was after 6 months or who were disease-free at last follow-up beyond 6 months were considered to be stable at 6 months and all other patients were not.	Assessed every 2 cycles for the first 12 cycles, then every 3 cycles until treatment discontinuation, then every 8 weeks until disease progression or up to 5 years
Overall Survival	Overall survival was defined as the time from randomization to death. Patients alive at last contact were censored on the date of last contact.	Assessed every 2 cycles for the first 12 cycles, then every 3 cycles until treatment discontinuation, then every 8 weeks until disease progression or up to 5 years
Objective Response Rate	Response was assessed using Solid Tumor Response Criteria (RECIST). Patients with complete responses or partial responses are considered having an objective response.	Assessed every 2 cycles for the first 12 cycles, then every 3 cycles until treatment discontinuation, then every 8 weeks until disease progression or up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Keith Flaherty, ECOG-ACRIN Cancer Research Group

Publications and helpful links

General Publications

• Flaherty KT, Manola JB, Pins M, McDermott DF, Atkins MB, Dutcher JJ, George DJ, Margolin KA, DiPaola RS. BEST: A Randomized Phase II Study of Vascular Endothelial Growth Factor, RAF Kinase, and Mammalian Target of Rapamycin Combination Targeted Therapy With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma--A Trial of the ECOG-ACRIN Cancer Research Group (E2804). J Clin Oncol. 2015 Jul 20;33(21):2384-91. doi: 10.1200/JCO.2015.60.9727. Epub 2015 Jun 15.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2007
• Primary Completion (Actual): February 7, 2014
• Study Completion (Actual): March 21, 2017

Study Registration Dates

• First Submitted: September 19, 2006
• First Submitted That Met QC Criteria: September 19, 2006
• First Posted (Estimate): September 21, 2006

Study Record Updates

• Last Update Posted (Actual): November 14, 2018
• Last Update Submitted That Met QC Criteria: October 15, 2018
• Last Verified: October 1, 2018

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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Antifungal Agents; Antibodies; Sorafenib; Immunoglobulins; Bevacizumab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Sirolimus; Immunoglobulin G; Endothelial Growth Factors
• Other Study ID Numbers: NCI-2009-00533 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180820 (U.S. NIH Grant/Contract); U10CA021115 (U.S. NIH Grant/Contract); ECOG-E2804; CDR0000499788; E2804 (Other Identifier: CTEP)