Postoperative Chemotherapy With or Without Bevacizumab for Patients With Stage II or III Rectal Cancer

Intergroup Randomized Phase III Study of Postoperative Oxaliplatin, 5-Fluorouracil and Leucovorin vs Oxaliplatin, 5-Fluorouracil, Leucovorin and Bevacizumab for Patients With Stage II or III Rectal Cancer Receiving Pre-operative Chemoradiation

Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving more than one drug (combination chemotherapy) together with bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known whether oxaliplatin, leucovorin, and fluorouracil is more effective with or without bevacizumab in treating rectal cancer. This randomized phase III trial is studying combination chemotherapy to see how well it works with or without bevacizumab in treating patients who have had surgery for stage II or stage III rectal cancer.

Study Overview

• Status: Terminated
• Conditions: Adenocarcinoma of the Rectum; Stage II Rectal Cancer; Stage III Rectal Cancer
• Intervention / Treatment: Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil; Drug: bevacizumab

Detailed Description

PRIMARY OBJECTIVES:

I. Compare the overall survival of patients who have undergone prior surgery and neoadjuvant chemoradiotherapy for clinical stage II or III rectal cancer treated with adjuvant oxaliplatin, leucovorin calcium, fluorouracil with vs without bevacizumab.

SECONDARY OBJECTIVES:

I. Evaluate tolerance of treatment, patterns of failure, and disease-free survival in patients treated with these regimens

EXPLORATORY OBJECTIVES:

I. Assess long-term rectal function using the Patient Bowel Function/Uniscale questionnaire and the Functional Assessment of Cancer (FACT)-Diarrhea subscale in patients treated with these regimens.

II. Validate the FACT-Diarrhea subscale. III. Assess long-term symptoms of oxaliplatin-related neurotoxicity using the FACT/Gynecologic Oncology Group (GOG)-Neurotoxicity subscale in patients treated with these regimens.

IV. Correlate TS, DPD and TP expression (key targets for fluorouracil); retention of chromosome 18q alleles and microsatellite instability (MSI) with TGFβ1RII mutation (markers for fluorouracil efficacy); ERCC1, ERCC2, and XPF expression (participants in repair of adducts from oxaliplatin); and p53 gene mutation and possibly other molecular markers pertinent to vascular endothelial growth factor in tumor tissue specimens with treatment efficacy in these patients.

V. Correlate tumor molecular prognostic markers (chromosome 18q allelic loss and MSI) with survival in patients treated with this regimen.

OUTLINE:

This is a randomized study. Patients are stratified according to Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1), clinical staging (high risk [T3, N+, M0 or T4, any N, M0] vs low risk [T1-2, N+, M0 or T3, N0, M0]), prior pre-operative oxaliplatin (yes vs no), and prior radiotherapy dose (40-50 Gy vs > 50-55.8 Gy). Patients are randomized to 1 of 2 treatment arms in a 1:1 ratio.

ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses* in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive bevacizumab** IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I*.

[Note: *Patients who received prior neoadjuvant oxaliplatin including patients on protocol NSABP-R-04 receive up to 9 courses of treatment followed by leucovorin calcium IV and fluorouracil IV with (arm II) or without (arm I) bevacizumab for up to 3 courses.]

[Note: **Patients no longer receive bevacizumab as of 4/29/2009 when accrual was terminated due to slow accrual for the study)]

Patients complete 10-15 minute questionnaires about bowel function at randomization, end of treatment, 12 months post-treatment and then annually to 5 years post-treatment.

After completion of study treatment, patients are followed periodically for approximately 10 years.

PROJECTED ACCRUAL: 2100 patients

• Study Type: Interventional
• Enrollment (Actual): 355
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Atlantic Health Sciences Corporation-Saint John Regional Hospital
  • Ontario
    • Kitchener, Ontario, Canada, N2G 1G3
      • Grand River Regional Cancer Centre at Grand River Hospital
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Mississauga, Ontario, Canada, L5M 2N1
      • Credit Valley Hospital
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa
    • Ottawa, Ontario, Canada, K1H 1C4
      • Ottawa Health Research Institute-General Division
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Thunder Bay Regional Health Science Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • Saint Michael's Hospital
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • CSSS Champlain-Charles Le Moyne
    • Quebec City, Quebec, Canada, G1R 2J6
      • CHUQ - Pavilion Hotel-Dieu de Quebec
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• Peru
  • Lima, Peru, Lima 34
    • Instituto Nacional de Enfermedades Neoplasicas
• Puerto Rico
  • San Juan, Puerto Rico, 00936
    • San Juan City Hospital
  • San Juan, Puerto Rico, 00919
    • I Gonzales Martinez-Oncologic Hospital
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Providence Hospital
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Saint Bernards Regional Medical Center
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center-Herrick Campus
    • Burlingame, California, United States, 94010
      • Mills - Peninsula Hospitals
    • 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
    • Fremont, California, United States, 94538
      • Valley Medical Oncology Consultants-Fremont
    • Fremont, California, United States, 94538
      • Kaiser Permanente, Fremont
    • Fresno, California, United States, 93720
      • Cancer Care Associates of Fresno Medical Group Inc
    • Fullerton, California, United States, 92835
      • Saint Jude Medical Center
    • Glendale, California, United States, 91204
      • Glendale Memorial Hospital and Health Center
    • Greenbrae, California, United States, 94904
      • Marin General Hospital
    • Hayward, California, United States, 94545
      • Saint Rose Hospital
    • Hayward, California, United States, 94545
      • Kaiser Permanente, Hayward
    • Los Angeles, California, United States, 90033
      • University of Southern California/Norris Cancer Center
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Marysville, California, United States, 95901
      • Fremont - Rideout Cancer Center
    • Monterey, California, United States, 93940
      • Community Hospital of Monterey Peninsula
    • 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, 94611
      • Kaiser Permanente-Oakland
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94609
      • Bay Area Tumor Institute CCOP
    • Oakland, California, United States, 94602
      • Highland General Hospital
    • Oakland, California, United States, 94609
      • Bay Area Breast Surgeons Inc
    • Oakland, California, United States, 94609
      • Larry G Strieff MD Medical Corporation
    • Oakland, California, United States, 94609
      • Tom K Lee Inc
    • Palm Springs, California, United States, 92262
      • Desert Regional Medical Center
    • Palo Alto, California, United States, 94301
      • Palo Alto Medical Foundation Heath Care
    • Pleasanton, California, United States, 94588
      • Valley Care Health System - Pleasanton
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants
    • Redwood City, California, United States, 94063
      • Kaiser Permanente-Redwood City
    • Richmond, California, United States, 94801
      • Kaiser Permanente-Richmond
    • Roseville, California, United States, 95661
      • Kaiser Permanente-Roseville
    • Sacramento, California, United States, 95823
      • Kaiser Permanente-South Sacramento
    • Sacramento, California, United States, 95825
      • Kaiser Permanente - Sacramento
    • Sacramento, California, United States, 95817
      • University of California at Davis Cancer Center
    • Salinas, California, United States, 93901
      • Salinas Valley Memorial
    • San Diego, California, United States, 92103
      • University of California at San Diego
    • San Diego, California, United States, 92120
      • Kaiser Permanente
    • San Francisco, California, United States, 94115
      • Kaiser Permanente-San Francisco
    • San Francisco, California, United States, 94118
      • California Pacific Medical Center
    • San Jose, California, United States, 95119
      • Kaiser Permanente-Santa Teresa-San Jose
    • 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
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente-South San Francisco
    • Stockton, California, United States, 95210
      • Kaiser Permanente-Stockton
    • Truckee, California, United States, 96161
      • Tahoe Forest Cancer Center
    • Vallejo, California, United States, 94589
      • Kaiser Permanente-Vallejo
    • Vallejo, California, United States, 94589
      • Sutter Solano Medical Center
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente-Walnut Creek
  • 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
    • Colorado Springs, Colorado, United States, 80909
      • Memorial Hospital Colorado Springs
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80218
      • Exempla Saint Joseph Hospital
    • Denver, Colorado, United States, 80224-2522
      • Colorado Cancer Research Program CCOP
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Fort Collins, Colorado, United States, 80528
      • Front Range Cancer Specialists
    • Grand Junction, Colorado, United States, 81502
      • 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
    • 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
      • Exempla Lutheran Medical Center
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology and Oncology Associates
  • 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
      • Washington Hospital Center
    • Washington, District of Columbia, United States, 20057
      • Lombardi Comprehensive Cancer Center at Georgetown University
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Jupiter, Florida, United States, 33458
      • Jupiter Medical Center
    • Lakeland, Florida, United States, 33805
      • The Watson Clinic
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center CCOP
    • Orange Park, Florida, United States, 32073
      • Cancer Specialists of North Florida-Orange Park
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer and Blood Center LLC
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Atlanta, Georgia, United States, 30342
      • Saint Joseph's Hospital of Atlanta
    • Atlanta, Georgia, United States, 30342
      • Atlanta Regional CCOP
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University
    • Austell, Georgia, United States, 30106
      • Well Star Cobb Hospital
    • Decatur, Georgia, United States, 30033
      • Dekalb Medical Center
    • Decatur, Georgia, United States, 30033
      • Atlanta VA Medical Center
    • Lawrenceville, Georgia, United States, 30045
      • Gwinnett Medical Center
    • Macon, Georgia, United States, 31208
      • Medical Center of Central Georgia
    • Marietta, Georgia, United States, 30060
      • Wellstar Kennestone Hospital
    • Riverdale, Georgia, United States, 30274
      • Southern Regional Medical Center
    • Rome, Georgia, United States, 30165
      • Harbin Clinic Medical Oncology and Clinical Research
    • Savannah, Georgia, United States, 31403
      • 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, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96859
      • Tripler Army Medical Center
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Oncare Hawaii Inc-POB II
    • Honolulu, Hawaii, United States, 96817
      • Oncare Hawaii Inc-Kuakini
    • 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
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Regional Medical Center
    • Idaho Falls, Idaho, United States, 83404
      • Hematology Oncology Associates of Eastern Idaho
    • Pocatello, Idaho, United States, 83201
      • Portneuf Medical Center
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Health
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Bloomington, Illinois, United States, 61701
      • Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital Association
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60608
      • Mount Sinai Hospital Medical Center
    • Chicago, Illinois, United States, 60625
      • Swedish Covenant Hospital
    • Chicago, Illinois, United States, 60611
      • Hematology and Oncology Associates
    • Chicago, Illinois, United States, 60631
      • Resurrection Healthcare
    • Chicago, Illinois, United States, 60612
      • Jesse Brown Veterans Affairs Medical Center
    • Chicago, Illinois, United States, 60612-3785
      • John H Stroger Jr Hospital of Cook County
    • Chicago, Illinois, United States, 60616
      • Mercy Hospital and Medical Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Downers Grove, Illinois, United States, 60515
      • Good Samaritan Hospital
    • Elmhurst, Illinois, United States, 60126
      • Elmhurst Memorial Hospital
    • Eureka, Illinois, United States, 61530
      • Eureka Hospital
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Evanston, Illinois, United States, 60202
      • Saint Francis Hospital
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare Galesburg
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hinsdale, Illinois, United States, 60521
      • Hinsdale Hematology Oncology Associates Incorporated
    • 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
      • Kewanee Hospital
    • Libertyville, Illinois, United States, 60048
      • North Shore Hematology Oncology
    • Macomb, Illinois, United States, 61455
      • McDonough District Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • 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
      • Sharis, Christine M MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Stoffel, Thomas J MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Vigliotti, Antonio, P.G. M.D. (UIA Investigator)
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Naperville, Illinois, United States, 60540
      • Edward Hospital/Cancer Center
    • 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
    • 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
      • Pekin Cancer Treatment Center
    • Pekin, Illinois, United States, 61554
      • Pekin Hospital
    • 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
    • Peoria, Illinois, United States, 61603
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61615-7827
      • OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CC
    • Peoria, Illinois, United States, 61615
      • Illinois Oncology Research Association CCOP
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Peru, Illinois, United States, 61354
      • Illinois Valley Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Rockford, Illinois, United States, 61104
      • Swedish American Hospital
    • Skokie, Illinois, United States, 60076
      • Hematology Oncology Associates of Illinois - Skokie
    • Skokie, Illinois, United States, 60076
      • Edward H Kaplan MD and Associates
    • Skokie, Illinois, United States, 60077
      • Midwest Cancer Research Group Incorporated
    • Spring Valley, Illinois, United States, 61362
      • Saint Margaret's Hospital
    • Springfield, Illinois, United States, 62781-0001
      • Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • Carle Clinic-Urbana Main
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • Saint Francis Hospital and Health Centers
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology Inc-Parkview
    • Indianapolis, Indiana, United States, 46260
      • Saint Vincent Hospital and Health Services
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Michigan City, Indiana, United States, 46360
      • Franciscan Saint Anthony Health-Michigan City
    • Mishawaka, Indiana, United States, 46545-1470
      • Saint Joseph Regional Medical Center-Mishawaka
    • Muncie, Indiana, United States, 47303
      • IU Health Ball Memorial Hospital
    • Newburgh, Indiana, United States, 47630
      • Oncology Hematology Associates of Southwest Indiana
    • Richmond, Indiana, United States, 47374
      • Reid Hospital and Health Care Services
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC-William R Bliss Cancer Center
    • Bettendorf, Iowa, United States, 52722
      • Constantinou, Costas L MD (UIA Investigator)
    • Cedar Rapids, Iowa, United States, 52403
      • Oncology Associates at Mercy Medical Center
    • Cedar Rapids, Iowa, United States, 52403
      • Cedar Rapids Oncology Association
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • 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, 50314
      • Medical Oncology and Hematology Associates-Laurel
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol
    • Des Moines, Iowa, United States, 50309
      • Iowa Oncology Research Association CCOP
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
    • Mason City, Iowa, United States, 50401
      • Mercy Medical Center - North Iowa
    • Sioux City, Iowa, United States, 51104
      • Saint Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51101-1733
      • Siouxland Regional Cancer Center
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology Oncology Associates
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center-Sioux City
    • Waterloo, Iowa, United States, 50702
      • Covenant Medical Center
    • Waterloo, Iowa, United States, 50701
      • Cedar Valley Medical Specialists
  • 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
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Olathe, Kansas, United States, 66061
      • Olathe Cancer Center
    • 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
    • Topeka, Kansas, United States, 66604
      • Stormont-Vail Regional Health Center
    • 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, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Main Office
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67214
      • Wichita CCOP
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • The James Graham Brown Cancer Center at University of Louisville
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
    • Lewiston, Maine, United States, 04240
      • Saint Mary's Regional Medical Center
    • Scarborough, Maine, United States, 04074
      • Maine Medical Center- Scarborough Campus
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Franklin Square Hospital Center
    • Easton, Maryland, United States, 21601
      • Memorial Hospital at Easton - Shore Regional Cancer Center
    • Elkton, Maryland, United States, 21921
      • Union Hospital of Cecil County
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Eastern Cooperative Oncology Group
    • Brighton, Massachusetts, United States, 02135-2997
      • Caritas Saint Elizabeth's Medical Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
    • Fitchburg, Massachusetts, United States, 01420
      • Simonds-Sinon Regional Cancer Center
    • Pittsfield, Massachusetts, United States, 01201
      • Berkshire Hematology Oncology PC
    • 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
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium Community Clinical Oncology Program
    • 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
      • Oakwood Hospital
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Escanaba, Michigan, United States, 49431
      • Green Bay Oncology - Escanaba
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Flint, Michigan, United States, 48532
      • Genesys Regional Medical Center-West Flint Campus
    • 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
      • Grand Rapids Clinical Oncology Program
    • Holland, Michigan, United States, 49423
      • Holland Community Hospital
    • Iron Mountain, Michigan, United States, 49801
      • Green Bay Oncology - Iron Mountain
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Marquette, Michigan, United States, 49855
      • Marquette General Hospital
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital
    • Monroe, Michigan, United States, 48162
      • Community Cancer Center of Monroe
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Muskegon, Michigan, United States, 49442
      • Mercy Health Partners-Hackley Campus
    • Pontiac, Michigan, United States, 48341-2985
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Saint Joseph Mercy Port Huron
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital-Royal Oak
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Hospital
    • 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
    • Bemidji, Minnesota, United States, 56601
      • Sanford Clinic North-Bemidgi
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Saint Mary's Medical Center
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Hospital
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Duluth Clinic CCOP
    • Edina, Minnesota, United States, 55435
      • Fairview-Southdale Hospital
    • 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
    • Mankato, Minnesota, United States, 56001
      • Mayo Clinic Health Systems-Mankato
    • 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
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis Veterans Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro-Minnesota CCOP
    • 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
      • Woodwinds Health Campus
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology and Hematology PA-Woodbury
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Hospital
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital-Joplin
    • 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, 63109
      • Saint Louis Cancer and Breast Institute-South City
    • Saint Louis, Missouri, United States, 63141
      • Saint John's Mercy Medical Center
    • 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
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • Montana Cancer Consortium CCOP
    • Billings, Montana, United States, 59102
      • Hematology-Oncology Centers of the Northern Rockies PC
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic
    • Billings, Montana, United States, 59107
      • Deaconess Medical Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • 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)
    • 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, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59801
      • Community Medical Hospital
    • Missoula, Montana, United States, 59802
      • Montana Cancer Specialists
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Nebraska Cancer Research Center
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegent Health Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68122
      • Alegent Health Immanuel Medical Center
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
    • Omaha, Nebraska, United States, 68106
      • Missouri Valley Cancer Consortium CCOP
  • 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
    • Exeter, New Hampshire, United States, 03833
      • Exeter Hospital
    • Keene, New Hampshire, United States, 03431
      • Cheshire Medical Center-Dartmouth-Hitchcock Keene
    • Manchester, New Hampshire, United States, 03103
      • Elliot Hospital
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • Ocean Medical Center
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Hamilton, New Jersey, United States, 08690
      • Cancer Institute of New Jersey At Hamilton
    • Long Branch, New Jersey, United States, 07740
      • Monmouth Medical Center
    • Montclair, New Jersey, United States, 07042
      • Mountainside Hospital
    • Morristown, New Jersey, United States, 07962
      • Morristown Memorial Hospital
    • Mount Holly, New Jersey, United States, 08060
      • Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
    • Ridgewood, New Jersey, United States, 07450
      • Valley Hospital
    • Sparta, New Jersey, United States, 07871
      • Sparta Cancer Treatment Center
    • Summit, New Jersey, United States, 07902
      • Overlook Hospital
    • Voorhees, New Jersey, United States, 08043
      • Virtua West Jersey Hospital Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87106
      • Hematology Oncology Associates
    • Albuquerque, New Mexico, United States, 87110
      • Presbyterian Kaseman Hospital
    • Santa Fe, New Mexico, United States, 87505
      • New Mexico Cancer Care Associates
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College of Medicine
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center
    • Brooklyn, New York, United States, 11203
      • Kings County Hospital
    • Brooklyn, New York, United States, 11203
      • University Hospital of Brooklyn
    • Brooklyn, New York, United States, 11203
      • State University of New York Downstate Medical Center
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • 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 PC-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, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Weill Medical College of Cornell University
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14620
      • Highland Hospital
    • Rochester, New York, United States, 14623
      • Interlakes Foundation Inc-Rochester
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
    • Syracuse, New York, United States, 13215
      • Community General Hospital
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital-Memorial Campus
    • Burlington, North Carolina, United States, 27216
      • Cone Health Alamance Regional Medical Center
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
    • Concord, North Carolina, United States, 28025
      • Carolinas Medical Center - Northeast
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
    • Wilson, North Carolina, United States, 27893
      • Wilson Medical Center
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Bismarck, North Dakota, United States, 58501
      • Bismarck Cancer Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic
    • Bismarck, North Dakota, United States, 58501
      • Saint Alexius Medical Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Clinic North-Fargo
    • Fargo, North Dakota, United States, 58122
      • Sanford Medical Center-Fargo
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center
  • Ohio
    • 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
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Clyde, Ohio, United States, 43410
      • North Coast Cancer Care-Clyde
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43210
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
    • 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 CCOP
    • 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, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45420
      • Dayton CCOP
    • Dayton, Ohio, United States, 45428
      • Veteran Affairs Medical Center
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • 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
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center Independence
    • Kenton, Ohio, United States, 43326
      • Cole, Sharon, K. M.D. (UIA Investigator)
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lancaster, Ohio, United States, 43130
      • Fairfield 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
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • 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
      • 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
    • Toledo, Ohio, United States, 43623
      • Stark, Michael, Edward. M.D. (UIA Investigator)
    • 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
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic Wooster Specialty Center
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis HealthCare System
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73120
      • Cancer Care Associates
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at Saint Francis
  • Oregon
    • Bend, Oregon, United States, 97701
      • Saint Charles Medical Center-Bend
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • 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
    • Portland, Oregon, United States, 97213
      • Western Oncology Research Consortium
    • Portland, Oregon, United States, 97216
      • Adventist Medical Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Allentown, Pennsylvania, United States, 18105
      • Lehigh Valley Hospital
    • 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, 17822-2001
      • Geisinger Medical Center
    • Kittanning, Pennsylvania, United States, 16201
      • Armstrong Center for Medicine and Health
    • Media, Pennsylvania, United States, 19063
      • Riddle Hospital
    • Paoli, Pennsylvania, United States, 19301
      • Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Medical 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, 19107
      • Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Cancer Center at Allegheny General Hospital
    • Pottstown, Pennsylvania, United States, 19464
      • Pottstown Memorial Medical Center
    • 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
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • Mainline Health CCOP
    • York, Pennsylvania, United States, 17405
      • WellSpan Health-York Hospital
  • Rhode Island
    • Cranston, Rhode Island, United States, 02920
      • Hematology and Oncology Associates of Rhode Island Inc
    • Warwick, Rhode Island, United States, 02886
      • Kent County Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Hospital
    • Charleston, South Carolina, United States, 29401
      • Roper Hospital
    • Florence, South Carolina, United States, 29506
      • McLeod Regional Medical Center
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Institute/Greenville CCOP
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Regional Medical Center
    • Spartanburg, South Carolina, United States, 29303
      • Upstate Carolina CCOP
  • South Dakota
    • 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
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Wellmont Holston Valley Hospital and Medical Center
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Center
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee - Memphis
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Nashville Oncology Associates PC
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC- Centennial Medical Center
    • Nashville, Tennessee, United States, 37208-3599
      • Meharry Medical College
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75235
      • Zale Lipshy University Hospital
    • Dallas, Texas, United States, 75390
      • Saint Paul Hospital
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center
    • Temple, Texas, United States, 76508
      • Scott and White Memorial Hospital
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital
    • Cedar City, Utah, United States, 84720
      • Sandra L Maxwell Cancer Center
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Murray, Utah, United States, 84157
      • Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604-3337
      • Utah Valley Regional Medical Center
    • Saint George, Utah, United States, 84770
      • Dixie Medical Center Regional Cancer Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists-Salt Lake City
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84103
      • Intermountain Health Care
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Charlottesville, Virginia, United States, 22901
      • Martha Jefferson Hospital
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology Inc
    • Hampton, Virginia, United States, 23666
      • Virginia Oncology Associates-Hampton
    • Harrisonburg, Virginia, United States, 22801
      • Rockingham Memorial Hospital Hahn Cancer Center
    • Lynchburg, Virginia, United States, 24501
      • Lynchburg Hematology-Oncology Clinic
    • Norton, Virginia, United States, 24273
      • Southwest VA Regional Cancer Center
  • Washington
    • Auburn, Washington, United States, 98001
      • Auburn Regional Medical Center
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Centralia, Washington, United States, 98531
      • Providence Centralia Hospital
    • Federal Way, Washington, United States, 98003
      • Saint Francis Hospital
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology and Oncology PLLC
    • Olympia, Washington, United States, 98506-5166
      • Providence - Saint Peter Hospital
    • Puyallup, Washington, United States, 98372
      • Good Samaritan Community Hospital
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative-Seattle
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98122
      • The Polyclinic
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99220
      • Rockwood Clinic
    • Tacoma, Washington, United States, 98431
      • Madigan Army Medical Center
    • Tacoma, Washington, United States, 98405
      • Saint Joseph Medical Center
    • Tacoma, Washington, United States, 98405
      • Allenmore Hospital
    • Tacoma, Washington, United States, 98415
      • Multicare Health System
    • Tacoma, Washington, United States, 98405
      • Northwest CCOP
    • Tacoma, Washington, United States, 98499
      • Saint Clare Hospital
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
    • Vancouver, Washington, United States, 98684
      • Compass Oncology Vancouver
  • West Virginia
    • Parkersburg, West Virginia, United States, 26101
      • Camden-Clark Memorial Hospital
  • Wisconsin
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Clinic Cancer Center at Sacred Heart
    • Eau Claire, Wisconsin, United States, 54701
      • Sacred Heart Hospital
    • Elkhorn, Wisconsin, United States, 53121
      • Aurora Cancer Care-Southern Lakes
    • Fond Du Lac, Wisconsin, United States, 54935
      • Agnesian Cancer Center
    • Glendale, Wisconsin, United States, 53212
      • Aurora Cancer Care-Glendale
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology Limited at Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54303
      • Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology at Saint Vincent Hospital
    • Janesville, Wisconsin, United States, 53547
      • Mercy Health System
    • La Crosse, Wisconsin, United States, 54601
      • Mayo Clinic Health System-Franciscan Healthcare
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic
    • Marshfield, Wisconsin, United States, 54449
      • Saint Joseph's Hospital
    • Milwaukee, Wisconsin, United States, 53215
      • Medical Consultants Limited
    • 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
      • Marshfield Clinic at James Beck Cancer Center
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Clinic-Rice Lake Center
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic-Sheboygan
    • 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
      • Marshfield Clinic - Weston Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Marshfield Clinic - Wisconsin Rapids Center
  • Wyoming
    • 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

Description

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the rectum meeting 1 of the following clinical (e.g., before neoadjuvant therapy) or pathologic staging criteria:

  • T3, N+, M0
  • T3, N0, M0
  • T4, N0, M0
  • Any T, N1-2, M0

• T4, N0-2, M0 disease must meet 1 of the following criteria:

  • Clinically fixed tumor on rectal examination with tumor adherent to the pelvic sidewall or sacrum
  • Hydronephrosis on Computed Tomography (CT) scan or Intravenous Pyelogram (IVP)
  • Ureteric or bladder invasion as documented by cystoscopy and cytology or biopsy
  • Invasion into prostate
  • Vaginal or uterine involvement
• Must have undergone complete tumor resection >= 28 days ago and able to begin treatment by day 56

• Must have undergone concurrent neoadjuvant chemoradiotherapy*

  • NOTE: *Neoadjuvant chemoradiotherapy received on protocol NSABP-R-04 allowed provided it met these criteria

• Must have undergone prior radiotherapy at 40-55.8 Gy** AND received 1 of the following chemotherapy regimens:

  • Continuous infusion of fluorouracil with or without oxaliplatin; fluorouracil and leucovorin calcium
  • Capecitabine with or without oxaliplatin; capecitabine with or without oxaliplatin OR a continuous infusion of fluorouracil with or without oxaliplatin received on protocol NSABP-R-04
  • NOTE: **Intensity-modulated radiotherapy allowed
• ECOG performance status 0-1
• Platelet count >= 100,000/mm^3
• Absolute granulocyte count >= 1,500/mm^3
• Bilirubin normal (unless chronic grade 1 bilirubin elevation due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin)
• Alkaline phosphatase (AP) < 2.5 times upper limit of normal (ULN) and aspartate aminotransferase (AST) < 1.5 times ULN
• Hepatitis B and C negative (for patients with AP > normal) unless previously vaccinated
• Serum creatinine =< 1.5 times ULN
• Urine protein:creatinine (UPC) ratio < 1.0 OR urine protein < 1 g on 24-hour urine collection
• International Normalized Ratio (INR) =< 1.5

• INR > 1.5 allowed provided patient is on full-dose anticoagulants AND meets all of the following criteria:

  • In-range INR (i.e., between 2 and 3) on a stable dose of warfarin or low molecular weight heparin
  • No active bleeding or pathological condition that is associated with a high risk of bleeding
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 3 months after study treatment
• No other previous or concurrent malignancy except nonmelanoma skin cancer, breast cancer in situ, carcinoma in situ of the cervix, or previously treated nonpelvic cancer that has been disease-free for > 5 years
• Patients with a history of breast cancer (without evidence of disease) who remain on hormonal therapy for > 5 years are eligible
• Patients with a history of hypertension must have blood pressure < 150/90 mm Hg AND be on a stable regimen of antihypertensive therapy
• No other prior chemotherapy or pelvic radiotherapy except as neoadjuvant treatment for current diagnosis of rectal cancer
• Concurrent participation on protocol NSABP-R-04 allowed

Exclusion Criteria:

• Pregnant or nursing
• Evidence of metastatic disease on the surgical/intraoperative examination
• Evidence of metastatic disease confirmed by CT scan, Magnetic resonance imaging (MRI), or ultrasound of the liver or chest CT scan or chest x-ray within the past 6 months
• Evidence of tumor outside of the pelvis, including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy
• Concurrent major surgery
• Active bleeding not related to the primary rectal tumor within the past 6 months
• Active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy
• Active gastroduodenal ulcer determined by endoscopy
• Serious or nonhealing wound, skin ulcer, or bone fracture
• Clinically significant peripheral sensory or motor neuropathy >= grade 2

• Nonmalignant systemic disease (e.g., cardiovascular, renal, or hepatic) that would preclude study treatment including, but not limited to, any of the following:

  • New York Heart Association class III or IV congestive heart failure
  • Concurrent symptomatic arrhythmia
• Transient ischemic attack or cerebrovascular accident
• Arterial thromboembolic event, unstable angina, or myocardial infarction within the past 12 months
• Significant peripheral vascular disease
• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude study requirements
• Significant traumatic injury within the past 28 days
• Known allergy to platinum compounds

• Prior invasive procedure, including either of the following:

  • Major surgical procedure or open biopsy within the past 28 days
  • Core biopsy or other minor procedure, except placement of a vascular access device, within the past 7 days

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I; Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses.	Drug: oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; L-OHP; Drug: leucovorin calcium; Given IV; Other Names: CF; CFR; LV; Drug: fluorouracil; Given IV; Other Names: 5-FU; 5-fluorouracil; 5-Fluracil
Experimental: Arm II; Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I.	Drug: oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; L-OHP; Drug: leucovorin calcium; Given IV; Other Names: CF; CFR; LV; Drug: fluorouracil; Given IV; Other Names: 5-FU; 5-fluorouracil; 5-Fluracil; Drug: bevacizumab; Given IV; Other Names: Avastin; anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; rhuMAb VEGF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year Overall Survival Rate	Overall survival (OS) was defined as time from randomization to date of death from any cause. Patients who were still alive were censored at last date of known alive. Kaplan-Meier method was used to estimate the 5-year OS rate.	Follow-up assessments performed every 3 months for patients < 2 years from randomization, every 6 months for patients 2-5 years from randomization, and every 12 months for patients 5-10 years from randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year Disease-free Survival Rate	Disease-free survival (DFS) was defined as time from randomization to recurrence, second invasive primary cancer or death, whichever occurred first. Patients who were still alive and had no DFS events were censored at the last disease assessment date known to be free of DFS events. Kaplan-Meier method was used to estimate 5-year DFS rate.	Follow-up assessments performed every 3 months for patients < 2 years from randomization, every 6 months for patients 2-5 years from randomization, and every 12 months for patients 5-10 years from randomization
Patterns of Failure	Failure included recurrence, second primary cancer and death without recurrence.	Follow-up assessments performed every 3 months for patients < 2 years from randomization, every 6 months for patients 2-5 years from randomization, and every 12 months for patients 5-10 years from randomization
Proportion of Patients Who Completed 12 Cycles of Treatment	In the study, treatment was repeated every 2 weeks for a total of 12 cycles on both arms. The total number of cycles of treatment patient received until going off treatment due to any reason was recorded. It was a measure of the tolerance of the therapy.	assessed at the end of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Rectal Function Between Baseline and 12 Months	Change in rectal function between baseline and 12 months was measuring the long-term rectal function among the patients. Rectal function was measured using the Bowel Function Questionnaire at baseline and 12 months after randomization. The total score of the questionnaire was calculated as the number of problems with bowel function (score range 0-11). Change in rectal function between baseline and 12 months= total score at 12 months - total score at baseline. A negative value indicated improved rectal function. This change in score was calculated for each individual patient who had the data.	assessed at baseline and 12 months after randomization
Change in Oxaliplatin-related Neurotoxicity Between Baseline and 12 Months	Change in oxaliplatin-related neurotoxicity between baseline and 12 months was measuring the long-term symptom of oxaliplatin-related neurotoxicity among the patients. Oxaliplatin-related neurotoxicity was measured using the FACT/GOG-Ntx subscale at baseline and 12 months after randomization. The range of the total score of the scale was between 0 and 44, and lower values indicate higher neurotoxicity. Change in oxaliplatin-related neurotoxicity between baseline and 12 months= total score at 12 months - total score at baseline. A negative value indicated worsened symptom. This change in score was calculated for each individual patient who had the data.	assessed at baseline and 12 months after randomization

Collaborators and Investigators

• Sponsor: ECOG-ACRIN Cancer Research Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Al Benson, Eastern Cooperative Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2006
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): February 11, 2019

Study Registration Dates

• First Submitted: March 15, 2006
• First Submitted That Met QC Criteria: March 15, 2006
• First Posted (Estimated): March 17, 2006

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Rectal cancer; Bevacizumab
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Antibodies; Fluorouracil; Oxaliplatin; Immunoglobulins; Bevacizumab; Leucovorin; Levoleucovorin; Antibodies, Monoclonal; Antineoplastic Agents, Immunological
• Other Study ID Numbers: E5204 (Other Identifier: ECOG-ACRIN Cancer Research Group); U10CA021115 (U.S. NIH Grant/Contract); NCI-2009-00563 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000467561 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.