Irinotecan and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer That Progressed During First-Line Therapy

Phase III Trial of Irinotecan-Based Chemotherapy Plus Cetuximab (NSC-714692) or Bevacizumab (NSC-704865) as Second-Line Therapy for Patients With Metastatic Colorectal Cancer Who Have Progressed on Bevacizumab With Either FOLFOX, OPTIMOX or XELOX

This randomized phase III trial is studying giving irinotecan and cetuximab together with bevacizumab to see how well it works compared with giving irinotecan and cetuximab alone in treating patients with metastatic colorectal cancer that progressed during first-line therapy. Drugs used in chemotherapy, such as irinotecan, 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 cetuximab and 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. It is not yet known whether irinotecan and cetuximab are more effective with or without bevacizumab in treating metastatic colorectal cancer.

Study Overview

• Status: Terminated
• Conditions: Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer
• Intervention / Treatment: Biological: bevacizumab; Drug: leucovorin calcium; Drug: fluorouracil; Biological: cetuximab; Drug: irinotecan hydrochloride

Detailed Description

PRIMARY OBJECTIVES:

I. Compare progression-free survival of patients with metastatic colorectal cancer that progressed on first-line therapy comprising bevacizumab and FOLFOX, OPTIMOX, or XELOX treated with irinotecan hydrochloride-based chemotherapy and cetuximab with vs without bevacizumab.

II. Compare overall survival of patients treated with these regimens. III. Compare objective tumor response (confirmed and unconfirmed, complete and partial response) in patients with measurable disease treated with these regimens.

IV. Compare the tolerability and safety profile of these regimens in these patients.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to Zubrod performance status (0 vs 1 or 2), discontinuation of oxaliplatin during first-line therapy (yes vs no), planned concurrent chemotherapy (FOLFIRI vs single-agent irinotecan hydrochloride), and time from last dose of bevacizumab (14-42 days vs >= 43 days).

All patients receive 1 of the following chemotherapy regimens:

SINGLE AGENT IRINOTECAN HYDROCHLORIDE: Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

FOLFIRI: Patients receive irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours on days 1 and 2. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Patients are then randomized to 1 of 3 treatment arms.

ARM I: Patients receive single-agent irinotecan hydrochloride or FOLFIRI as outlined above and cetuximab IV over 1-2 hours on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive single-agent irinotecan hydrochloride or FOLFIRI as outlined above and cetuximab as in arm I. Patients also receive bevacizumab IV over 30 minutes on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity.

ARM III (closed to accrual as of 4/20/2009): Patients receive single-agent irinotecan hydrochloride or FOLFIRI as outlined above and cetuximab as in arm I. Patients also receive a higher dose of bevacizumab (higher than in arm II) IV over 30 minutes on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months for 2 years and then once a year for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Ft. Smith, Arkansas, United States, 72903
      • Saint Edward Mercy Medical Center
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer 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
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • Fairfield, California, United States, 94533
      • Northbay Cancer Center
    • 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 General Hospital
    • Hayward, California, United States, 94545
      • Saint Rose Hospital
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Marysville, California, United States, 95901
      • Fremont - Rideout Cancer Center
    • 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
    • Pismo Beach, California, United States, 93449
      • Palchak David MD
    • Pleasanton, California, United States, 94588
      • Valley Care Health System - Pleasanton
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants
    • Roseville, California, United States, 95661
      • Sutter Roseville Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
    • San Pablo, California, United States, 94806
      • Doctors Medical Center- JC Robinson Regional Cancer Center
    • Truckee, California, United States, 96161
      • Tahoe Forest Cancer Center
  • 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
    • 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
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • Delaware
    • Dover, Delaware, United States, 19901
      • Bayhealth Medical Center at Kent General
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Lombardi Comprehensive Cancer Center at Georgetown University
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Jacksonville, Florida, United States, 32207
      • Edna Williams Cancer Center at the Baptist Cancer Institute
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Titusville, Florida, United States, 32796
      • Space Coast Cancer Centers-Titusville
  • Georgia
    • 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
    • Austell, Georgia, United States, 30106
      • Well Star Cobb Hospital
    • Columbus, Georgia, United States, 31904
      • John B Amos Cancer Center
    • 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
    • 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
    • Valdosta, Georgia, United States, 31603
      • South Georgia Medical Center
  • Illinois
    • 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, 60631
      • Resurrection Healthcare
    • Chicago, Illinois, United States, 60612-3785
      • John H Stroger Jr Hospital of Cook County
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Effingham, Illinois, United States, 62401
      • Saint Anthony Memorial Hospital
    • Eureka, Illinois, United States, 61530
      • Eureka Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare Galesburg
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hopedale, Illinois, United States, 61747
      • Hopedale Medical Complex - Hospital
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates Limited
    • La Grange, Illinois, United States, 60525
      • Adventist La Grange Memorial Hospital
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • 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
      • Illinois Oncology Research Association CCOP
    • Peru, Illinois, United States, 61354
      • Illinois Valley Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • 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
    • 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
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • Indiana University 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
    • Mishawaka, Indiana, United States, 46545-1470
      • Michiana Hematology Oncology PC-Mishawaka
    • Plymouth, Indiana, United States, 46563
      • Michiana Hematology Oncology PC-Plymouth
    • 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-William R Bliss Cancer Center
    • Bettendorf, Iowa, United States, 52722
      • Hematology Oncology Associates-Quad Cities
    • Cedar Rapids, Iowa, United States, 52403
      • Mercy Hospital
    • Cedar Rapids, Iowa, United States, 52403
      • Oncology Associates at Mercy Medical Center
    • Cedar Rapids, Iowa, United States, 52403
      • Cedar Rapids Oncology Association
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 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
    • Sioux City, Iowa, United States, 51104
      • Saint Luke's Regional Medical 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
  • Kansas
    • 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
    • Hays, Kansas, United States, 67601
      • Hays Medical Center
    • Hutchinson, Kansas, United States, 65702
      • Promise Regional Medical Center-Hutchinson
    • 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
    • Liberal, Kansas, United States, 67901
      • Cancer Center of Kansas-Liberal
    • 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
    • Pittsburg, Kansas, United States, 66762
      • Via Christi Hospital-Pittsburg
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Salina Regional Health Center
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Topeka, Kansas, United States, 66606
      • Saint Francis Hospital and Medical Center - Topeka
    • 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, 40215
      • Doctors Carrol, Sheth, Raghavan
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70806
      • Baton Rouge General Medical Center
  • Maine
    • Augusta, Maine, United States, 04330
      • Harold Alfond Center for Cancer Care
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
  • Maryland
    • Easton, Maryland, United States, 21601
      • Memorial Hospital at Easton - Shore Regional Cancer Center
    • Frederick, Maryland, United States, 21701
      • Frederick Memorial Hospital
  • Massachusetts
    • Attleboro, Massachusetts, United States, 02703
      • Sturdy Memorial Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Bixby Medical Center
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium Community Clinical Oncology Program
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • 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
      • 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
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital
    • Monroe, Michigan, United States, 48162
      • Community Cancer Center of Monroe
    • Muskegon, Michigan, United States, 49442
      • Mercy Health Partners-Hackley Campus
    • Niles, Michigan, United States, 49120
      • Michiana Hematology Oncology PC-Niles
    • 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
      • Marie Yeager Cancer Center
    • St. Joseph, Michigan, United States, 49085
      • Lakeland Hospital
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Minnesota
    • 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
    • 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
    • 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
    • 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
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Singing River Hospital
  • Missouri
    • Cape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Hospital
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel
    • Columbia, Missouri, United States, 65201
      • Veterans Administration
    • 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
      • Center for Cancer Care and Research
    • 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
    • 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
    • Kearney, Nebraska, United States, 68847
      • Good Samaritan Hospital
    • Lincoln, Nebraska, United States, 68510
      • Nebraska Cancer Research Center
  • New Jersey
    • Mount Holly, New Jersey, United States, 08060
      • Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
    • Sparta, New Jersey, United States, 07871
      • Sparta Cancer Treatment Center
    • Voorhees, New Jersey, United States, 08043
      • Virtua West Jersey Hospital Voorhees
  • New York
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center
    • Buffalo, New York, United States, 14215
      • Veterans Affairs Western New York Health Care System-Buffalo
    • Clifton Springs, New York, United States, 14432
      • Finger Lakes Hematology and Oncology
    • Glens Falls, New York, United States, 12801
      • Glens Falls Hospital
    • Glens Falls, New York, United States, 12801
      • Adirondack Cancer Center
    • Middletown, New York, United States, 10940
      • Orange Regional Medical Center
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center-Goldsboro
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
    • Kinston, North Carolina, United States, 28501
      • Kinston Medical Specialists PA
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth of the Carolinas-Moore Regional Hosiptal
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
  • 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
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • Akron General Medical Center
    • 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
    • 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 CCOP
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Elyria, Ohio, United States, 44035
      • Hematology Oncology Center Incorporated
    • Elyria, Ohio, United States, 44035
      • Community Health Partners Regional Medical Center
    • Fremont, Ohio, United States, 43420
      • Fremont Memorial Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Mansfield, Ohio, United States, 44903
      • Mansfield General Hospital-MedCentral Health System
    • 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
      • 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
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System
  • Oregon
    • Coos Bay, Oregon, United States, 97420
      • Bay Area Hospital
    • Portland, Oregon, United States, 97216
      • Adventist Medical Center
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-2001
      • Geisinger Medical Center
    • Darby, Pennsylvania, United States, 19023-1291
      • Mercy Fitzgerald Hospital
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazelton
    • Lemoyne, Pennsylvania, United States, 17043
      • Central PA Hematology-Medical Oncology Associates PC
    • Media, Pennsylvania, United States, 19063
      • Riddle Hospital
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Cancer Center at Allegheny General Hospital
    • Scranton, Pennsylvania, United States, 18508
      • Hematology and Oncology Associates of North East Pennsylvania
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • Upland, Pennsylvania, United States, 19013
      • Associates In Hematology Oncology PC-Upland
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Hospital
    • Columbia, South Carolina, United States, 29210
      • South Carolina Oncology Associates PA
    • Easley, South Carolina, United States, 29640
      • Greenville Health System Cancer Institute-Easley
    • Florence, South Carolina, United States, 29506
      • McLeod Regional Medical Center
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Andrews
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Faris
    • Greenville, South Carolina, United States, 29605
      • Greenville Memorial Hospital
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Butternut
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Instutite/Greenville CCOP
    • Greenwood, South Carolina, United States, 29646
      • Self Regional Healthcare
    • Greer, South Carolina, United States, 29650
      • Greenville Health System Cancer Institute-Greer
    • Greer, South Carolina, United States, 29650
      • Cancer Centers of the Carolinas-Greer Medical Oncology
    • Seneca, South Carolina, United States, 29672
      • Greenville Health System Cancer Institute-Seneca
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System Cancer Institute-Spartanburg
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Regional Medical Center
    • Spartanburg, South Carolina, United States, 29303
      • Upstate Carolina CCOP
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee - Memphis
  • Texas
    • Amarillo, Texas, United States, 79106
      • The Don and Sybil Harrington Cancer Center
    • Temple, Texas, United States, 76508
      • Scott and White Memorial Hospital
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology Inc
  • 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
      • Columbia Basin Hematology and Oncology PLLC
    • 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, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    • Seattle, Washington, United States, 98104
      • Harborview 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
    • Sedro-Woolley, Washington, United States, 98284
      • United General Hospital
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology PS
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Medical Center
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Charleston
    • Parkersburg, West Virginia, United States, 26101
      • Camden-Clark Memorial Hospital
  • Wisconsin
    • Eau Claire, Wisconsin, United States, 54702
      • Midelfort Clinic-Clairemont Campus
    • Eau Claire, Wisconsin, United States, 54703
      • Mayo Clinic Health System Eau Claire Hospital - Luther Campus
    • Elkhorn, Wisconsin, United States, 53121
      • Aurora Cancer Care-Southern Lakes
    • 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
    • Manitowoc, Wisconsin, United States, 54221
      • Holy Family Memorial Hospital
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Mequon, Wisconsin, United States, 53097
      • Columbia Saint Mary's Hospital - Ozaukee
    • Milwaukee, Wisconsin, United States, 53211
      • Columbia Saint Mary's Water Tower Medical Commons
    • Milwaukee, Wisconsin, United States, 53215
      • Medical Consultants Limited
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology - Oconto Falls
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology - Sturgeon Bay
  • 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 must have metastatic colorectal cancer that has been histologically or cytologically confirmed; confirmation may be from either the primary tumor or a metastasis; patients must have wild type KRAS
• Patients must be registered within 28 days of documented disease progression on first line chemotherapy with bevacizumab plus either FOLFOX, OPTIMOX, or XELOX; this progression must have occurred within 90 days after the last dose of bevacizumab; patients who discontinued oxaliplatin, continued with 5-FU/LV or capecitabine and bevacizumab and then had subsequent progression while on fluoropyrimidine and bevacizumab are eligible; patients who discontinued bevacizumab due to adverse events in the first-line setting are not eligible
• Measurable or nonmeasurable disease
• At least 14 days must have elapsed since the last dose of first line chemotherapy and bevacizumab
• Patients must not have received prior treatment with irinotecan (either as adjuvant or metastatic treatment)
• Patients must have no history of prior treatment with cetuximab or other agents targeting VEGF or EGFR (except for bevacizumab)
• Prior radiotherapy is allowed, provided at least 28 days have elapsed since the last treatment; all adverse events related to radiation therapy must be resolved
• Prior surgery is allowed, provided at least 28 days have elapsed since any major surgery and patient has recovered from all effects
• Zubrod performance status 0-2
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Hemoglobin >= 9 g/dL
• Total bilirubin =< 1.5 times upper limit of normal (ULN)
• Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvate transaminase (SGPT) =< 2.5 x IULN; if there are known liver metastases, SGOT or SGPT must be =< 5 x IULN; these results must be obtained within 28 days prior to registration
• Serum creatinine =< IULN or measured or estimated creatinine clearance >= 60 mL/min
• Patients must not have a history or known presence of brain metastasis
• Patients may be on full dose anticoagulation with warfarin provided that the patient has an acceptable International Normalized Ratio (INR) (between 2 and 3), obtained within 28 days prior to registration
• No clinically relevant bleeding diathesis or coagulopathy
• Patients must not have experienced nephrotic range proteinuria from prior bevacizumab therapy; urine protein must be screened by urine analysis for Urine Protein Creatinine (UPC) ratio; for UPC ratio > 0.5, 24-hour urine protein must be obtained and the level must be < 1,000 mg for patient enrollment; urine protein and creatinine used in calculating the UPC ratio must be obtained within 28 days prior to registration
• No uncontrolled high blood pressure (BP) (i.e., systolic BP > 150 mm Hg and diastolic BP > 90 mm Hg)

• No cardiovascular event within the past 6 months, including any of the following:

  • Arterial thrombosis
  • Unstable angina
  • Myocardial infarction
  • Cerebrovascular accident
• Patients must not have New York Heart Association (NYHA) >= Grade 2 congestive heart failure
• Patients must not have unstable symptomatic arrhythmia requiring medication; (patients with chronic, controlled arrhythmias such as atrial fibrillation or paroxysmal supraventricular tachycardia [PSVT] are eligible)
• No clinically significant peripheral vascular disease
• No serious or nonhealing active wound, ulcer, or bone fracture
• No history of gastrointestinal (GI) perforation while on prior bevacizumab
• No significant bleeding episodes (e.g., hemoptysis or upper or lower GI bleeding) within the past 6 months unless the source of bleeding has been resected
• No known hypersensitivity to bevacizumab or known potential hypersensitivity to cetuximab
• No other concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any other type of anticancer treatment
• Due to the possibility of harm to a fetus or nursing infant from this treatment regimen, patients must not be pregnant or nursing; women and men of reproductive potential must have agreed to use an effective contraceptive method
• No other malignancy within the past 5 years except for adequately treated basal or squamous cell skin cancer or cervical cancer in situ
• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm I (chemotherapy, cetuximab); Patients receive single-agent irinotecan hydrochloride IV or FOLFIRI IV. They also receive cetuximab IV over 1-2 hours on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity.	Drug: leucovorin calcium; Given IV; Other Names: CF; CFR; LV; Drug: fluorouracil; Given IV; Other Names: 5-FU; 5-fluorouracil; 5-Fluracil; Biological: cetuximab; Given IV; Other Names: C225; IMC-C225; C225 monoclonal antibody; MOAB C225; monoclonal antibody C225; Drug: irinotecan hydrochloride; Given IV; Other Names: irinotecan; Campto; Camptosar; U-101440E; CPT-11
EXPERIMENTAL: Arm II (chemotherapy, cetuximab, bevacizumab); Patients receive single-agent irinotecan hydrochloride or FOLFIRI AND cetuximab as in arm I. Patients also receive bevacizumab IV over 30 minutes on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity.	Biological: bevacizumab; Given IV; Other Names: Avastin; anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; rhuMAb VEGF; Drug: leucovorin calcium; Given IV; Other Names: CF; CFR; LV; Drug: fluorouracil; Given IV; Other Names: 5-FU; 5-fluorouracil; 5-Fluracil; Biological: cetuximab; Given IV; Other Names: C225; IMC-C225; C225 monoclonal antibody; MOAB C225; monoclonal antibody C225; Drug: irinotecan hydrochloride; Given IV; Other Names: irinotecan; Campto; Camptosar; U-101440E; CPT-11
EXPERIMENTAL: Arm III (closed to accrual as of 4/20/2009); Patients receive single-agent irinotecan hydrochloride or FOLFIRI AND cetuximab as in arm I. Patients also receive a higher dose of bevacizumab (higher than in arm II) IV over 30 minutes on day 1. Courses repeat every 14-21 days (depending upon chemotherapy regimen) in the absence of disease progression or unacceptable toxicity.	Biological: bevacizumab; Given IV; Other Names: Avastin; anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; rhuMAb VEGF; Drug: leucovorin calcium; Given IV; Other Names: CF; CFR; LV; Drug: fluorouracil; Given IV; Other Names: 5-FU; 5-fluorouracil; 5-Fluracil; Biological: cetuximab; Given IV; Other Names: C225; IMC-C225; C225 monoclonal antibody; MOAB C225; monoclonal antibody C225; Drug: irinotecan hydrochloride; Given IV; Other Names: irinotecan; Campto; Camptosar; U-101440E; CPT-11

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	PFS is measured from date of registration to first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time to death is from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.	Up to 5 years
Objective Tumor Response		Up to 5 years
Toxicity	Number of patients with Grade 3 through 5 adverse events that are related to study drug. Only adverse events that are possibly, probably or definitely related to study drug are reported.	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Eastern Cooperative Oncology Group; NCIC Clinical Trials Group; Cancer and Leukemia Group B; North Central Cancer Treatment Group
• Investigators: Principal Investigator: Philip Gold, Southwest Oncology Group

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (ACTUAL): November 1, 2012
• Study Completion (ACTUAL): November 1, 2012

Study Registration Dates

• First Submitted: July 10, 2007
• First Submitted That Met QC Criteria: July 10, 2007
• First Posted (ESTIMATE): July 11, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): July 31, 2014
• Last Update Submitted That Met QC Criteria: July 25, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Recurrence; Rectal Neoplasms; Colonic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Antibodies; Fluorouracil; Immunoglobulins; Bevacizumab; Leucovorin; Irinotecan; Levoleucovorin; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: NCI-2009-00784 (REGISTRY: CTRP (Clinical Trial Reporting Program)); U10CA032102 (U.S. NIH Grant/Contract); CALGB-SWOG-S0600; SWOG-S0600; CDR0000551934; ECOG-SWOG-S0600; CAN-NCIC-SWOG-S0600; NCCTG-SWOG-S0600; S0600 (OTHER: CTEP)