Fulvestrant With or Without Lapatinib in Treating Postmenopausal Women With Stage III or Stage IV Breast Cancer That is Hormone Receptor-Positive

Endocrine Therapy With or Without Inhibition of EGF and HER2 Growth Factor Receptors: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Fulvestrant With or Without Lapatinib (GW572016) for Postmenopausal Women With Hormone Receptor Positive Advanced Breast Cancer

This randomized phase III trial studies fulvestrant and lapatinib to see how well they work compared to fulvestrant and a placebo in treating postmenopausal women with stage III or stage IV breast cancer that is hormone receptor-positive. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by lowering the amount of estrogen the body makes. Lapatinib may stop the growth of breast cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether fulvestrant is more effective with or without lapatinib in treating breast cancer.

Study Overview

• Status: Completed
• Conditions: Recurrent Breast Carcinoma; Estrogen Receptor Positive; HER2/Neu Negative; Progesterone Receptor Positive; HER2 Positive Breast Carcinoma; Stage IV Breast Cancer AJCC v6 and v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Drug: Lapatinib Ditosylate; Drug: Fulvestrant

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the effect, in terms of progression free survival, of the antiestrogen fulvestrant alone with fulvestrant administered in combination with the dual-kinase inhibitor lapatinib for postmenopausal women with estrogen receptor (ER) and/or progesterone receptor (PgR) positive advanced breast cancer.

SECONDARY OBJECTIVES:

I. To compare the effects of fulvestrant alone with fulvestrant and lapatinib on other clinical endpoints, including response rate, response and stable disease rate (complete response [CR] + partial response [PR] + stable disease >= 6 months), duration of response, overall survival, symptom checklist scores, and toxicity.

II. To define predictive markers of clinical activity among women receiving fulvestrant with or without lapatinib.

III. To determine if the clinical benefits for combination of hormonal and growth factor inhibitor therapy are most pronounced in women whose tumors express higher levels of ER, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), phosphorylated protein kinase B (pAkt), and/or phosphorylated mitogen-activated protein kinase 1/2 (pERK1/2).

IV. To serologically determine if HER2 extracellular domain (ECD) and EGFR ECD levels can identify patients with a greater likelihood of response and clinical benefit to fulvestrant with or without lapatinib.

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

ARM I: Patients receive lapatinib ditosylate orally (PO) once daily (QD) on days 1-28 and fulvestrant intramuscularly (IM) on days 1 and 15 of course 1 and on day 1 of each subsequent course.

ARM II: Patients receive placebo PO QD on days 1-28 and fulvestrant as in Arm I.

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

After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Arroyo Grande, California, United States, 93420
      • PCR Oncology
    • Arroyo Grande, California, United States, 93420
      • Arroyo Grande Community
    • 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
    • Emeryville, California, United States, 94608
      • Bay Area Breast Surgeons Inc
    • Fremont, California, United States, 94538
      • Valley Medical Oncology Consultants-Fremont
    • Glendale, California, United States, 91204
      • Glendale Memorial Hospital and Health Center
    • Hayward, California, United States, 94545
      • Saint Rose Hospital
    • Marysville, California, United States, 95901
      • Fremont - Rideout Cancer Center
    • Mountain View, California, United States, 94040
      • El Camino Hospital
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Camino Division
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94609
      • Hematology and Oncology Associates-Oakland
    • Oakland, California, United States, 94602
      • Highland General Hospital
    • Oakland, California, United States, 94609
      • Tom K Lee Inc
    • Oakland, California, United States, 94609
      • Bay Area Tumor Institute
    • Pleasanton, California, United States, 94588
      • Valley Care Health System - Pleasanton
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • Salinas, California, United States, 93901
      • Salinas Valley Memorial
    • San Diego, California, United States, 92108
      • Kaiser Permanente-San Diego Mission
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital
    • San Pablo, California, United States, 94806
      • Doctors Medical Center- JC Robinson Regional Cancer Center
    • Truckee, California, United States, 96161
      • Gene Upshaw Memorial Tahoe Forest Cancer Center
    • Vacaville, California, United States, 95687
      • Northbay Cancer Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • UCHealth Memorial Hospital Central
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Saint Vincent's Medical Center
    • New Haven, Connecticut, United States, 06520
      • Yale University
    • Torrington, Connecticut, United States, 06790
      • Smilow Cancer Hospital-Torrington Care Center
    • Waterbury, Connecticut, United States, 06708
      • Harold Leever Regional Cancer Center
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
    • Washington, District of Columbia, United States, 20016
      • Sibley Memorial Hospital
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital
  • Idaho
    • Boise, Idaho, United States, 83712
      • Saint Luke's Mountain States Tumor Institute
    • 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, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Heartland Cancer Research NCORP
    • Eureka, Illinois, United States, 61530
      • Eureka Hospital
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • 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
    • Kankakee, Illinois, United States, 60901
      • Presence Saint Mary's Hospital
    • Kewanee, Illinois, United States, 61443
      • Kewanee Hospital
    • La Grange, Illinois, United States, 60525
      • AMITA Health Adventist Medical Center
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center Foundation
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • 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
      • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
    • Pekin, Illinois, United States, 61554
      • Pekin Hospital
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Peru, Illinois, United States, 61354
      • Illinois Valley Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • River Forest, Illinois, United States, 60305
      • West Suburban Medical Center
    • Rockford, Illinois, United States, 61108
      • OSF Saint Anthony Medical Center
    • Spring Valley, Illinois, United States, 61362
      • Saint Margaret's Hospital
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • Franciscan Saint Francis Health-Beech Grove
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Elkhart, Indiana, United States, 46514-2098
      • Elkhart Clinic
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology Inc-Parkview
    • Goshen, Indiana, United States, 46526
      • Goshen Center for Cancer Care
    • Indianapolis, Indiana, United States, 46219
      • Community Cancer Center East
    • Indianapolis, Indiana, United States, 46256
      • Community Cancer Center North
    • 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
      • Saint Joseph Regional Medical Center-Mishawaka
    • Richmond, Indiana, United States, 47374
      • Reid Health
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • Michiana Hematology Oncology PC-South Bend
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC - Ames
    • Bettendorf, Iowa, United States, 52722
      • University of Iowa Healthcare Cancer Services Quad Cities
    • Cedar Rapids, Iowa, United States, 52403
      • Mercy Hospital
    • Cedar Rapids, Iowa, United States, 52403
      • Oncology Associates at Mercy Medical Center
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • Council Bluffs, Iowa, United States, 51503
      • Heartland Oncology and Hematology LLP
    • Davenport, Iowa, United States, 52803
      • Genesis Medical Center - East Campus
    • Davenport, Iowa, United States, 52804
      • Genesis Cancer Care Institute
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50309
      • Iowa-Wide Oncology Research Coalition NCORP
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates-Laurel
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • Mason City, Iowa, United States, 50401
      • Mercy Medical Center - North Iowa
    • Ottumwa, Iowa, United States, 52501
      • Ottumwa Regional Health Center
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
    • Sioux City, Iowa, United States, 51102
      • Mercy Medical Center-Sioux City
    • Sioux City, Iowa, United States, 51104
      • Saint Luke's Regional Medical Center
  • 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 Cancer Center
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67905
      • Cancer Center of Kansas-Liberal
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • 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
      • Cancer Center of Kansas - Salina
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Cancer Center / Stormont Vail Health
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Kentucky
    • Louisville, Kentucky, United States, 40215
      • Doctors Carrol, Sheth, Raghavan
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center
    • Baton Rouge, Louisiana, United States, 70806
      • Baton Rouge General Medical Center
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Science Center
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
    • York, Maine, United States, 03909
      • York Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Baltimore, Maryland, United States, 21229
      • Saint Agnes Hospital
    • Easton, Maryland, United States, 21601
      • University of Maryland Shore Medical Center at Easton
    • Elkton, Maryland, United States, 21921
      • Union Hospital of Cecil County
    • Frederick, Maryland, United States, 21701
      • Frederick Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Fall River, Massachusetts, United States, 02721
      • Saint Anne's Hospital
    • Gloucester, Massachusetts, United States, 01930
      • Addison Gilbert Hospital
    • Lowell, Massachusetts, United States, 01854
      • Lowell General Hospital
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center - University Campus
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Big Rapids, Michigan, United States, 49307
      • Spectrum Health Big Rapids Hospital
    • Escanaba, Michigan, United States, 49829
      • Green Bay Oncology - Escanaba
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Grand Rapids, Michigan, United States, 49503
      • Cancer Research Consortium of West Michigan NCORP
    • Holland, Michigan, United States, 49423
      • Holland Community Hospital
    • Iron Mountain, Michigan, United States, 49801
      • Green Bay Oncology - Iron Mountain
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Medical Center
    • Midland, Michigan, United States, 48670
      • Mid-Michigan Medical Center - Midland
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Muskegon, Michigan, United States, 49442
      • Mercy Health Partners-Hackley Campus
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital-Royal Oak
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center Saint Joseph
    • Saint Joseph, Michigan, United States, 49085
      • Marie Yeager Cancer Center
    • Saint Joseph, Michigan, United States, 49085
      • Oncology Care Associates PLLC
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • Saint Luke's Hospital of Duluth
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Cancer Center
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Saint Mary's Medical Center
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview-Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Litchfield, Minnesota, United States, 55355
      • Meeker County Memorial Hospital
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro Minnesota Community Oncology Research Consortium
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Saint Paul, Minnesota, United States, 55102
      • Saint Joseph's Hospital - Healtheast
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
    • Woodbury, Minnesota, United States, 55125
      • Woodwinds Health Campus
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
    • Keesler Air Force Base, Mississippi, United States, 39534
      • Keesler Medical Center
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Hospital
    • Chesterfield, Missouri, United States, 63017
      • Saint Luke's Hospital
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel
    • Columbia, Missouri, United States, 65201
      • Missouri Cancer Associates
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63141
      • Saint Louis-Cape Girardeau CCOP
    • Saint Louis, Missouri, United States, 63141
      • Center for Cancer Care and Research
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59102
      • Montana Cancer Consortium NCORP
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59102
      • Saint Vincent Frontier Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Great Falls, Montana, United States, 59405
      • Berdeaux, Donald MD (UIA Investigator)
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology
    • Missoula, Montana, United States, 59804
      • Community Medical Hospital
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59802
      • Montana Cancer Specialists
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • New Hampshire Oncology Hematology PA-Concord
    • Hooksett, New Hampshire, United States, 03106
      • New Hampshire Oncology Hematology PA-Hooksett
    • Laconia, New Hampshire, United States, 03246
      • LRGHealthcare-Lakes Region General Hospital
    • Manchester, New Hampshire, United States, 03103
      • Elliot Hospital
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • Summit, New Jersey, United States, 07902
      • Overlook Hospital
    • Trenton, New Jersey, United States, 08629
      • Saint Francis Medical Center
    • Vineland, New Jersey, United States, 08360
      • Inspira Medical Center Vineland
    • Voorhees, New Jersey, United States, 08043
      • Virtua Voorhees
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of Central New York-East Syracuse
    • Mount Kisco, New York, United States, 10549
      • Northern Westchester Hospital
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Staten Island, New York, United States, 10305
      • Staten Island University Hospital
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Gastonia, North Carolina, United States, 28054
      • CaroMont Regional Medical Center
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center-Goldsboro
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Henderson, North Carolina, United States, 27536
      • Maria Parham Hospital
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
    • Kinston, North Carolina, United States, 28501
      • Vidant Oncology-Kinston
    • Lumberton, North Carolina, United States, 28358
      • Southeastern Regional Medical Center
    • Oxford, North Carolina, United States, 27565
      • Granville Medical Center
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth of the Carolinas-Moore Regional Hospital
    • Raleigh, North Carolina, United States, 27609
      • Duke Raleigh Hospital
    • Roxboro, North Carolina, United States, 27573
      • Person Memorial Hospital
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic
    • Bismarck, North Dakota, United States, 58501
      • Saint Alexius Medical Center
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center
    • Minot, North Dakota, United States, 58701
      • Trinity Cancer Care Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • Cleveland Clinic Akron General
    • Bellefontaine, Ohio, United States, 43311
      • Mary Rutan Hospital
    • Canton, Ohio, United States, 44710
      • Aultman Health Foundation
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • 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
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Miami Valley Hospital North
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45428
      • Dayton Veterans Affairs Medical Center
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center Independence
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lima, Ohio, United States, 45801
      • Saint Rita's Medical Center
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical 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 Family Health and Surgery Center
    • Wright-Patterson Air Force Base, Ohio, United States, 45433-5529
      • Wright-Patterson Medical Center
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System Cancer Care Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Bethlehem, Pennsylvania, United States, 18015
      • Saint Luke's University Hospital-Bethlehem Campus
    • Langhorne, Pennsylvania, United States, 19047
      • Saint Mary Medical and Regional Cancer Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Hospital
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute - Eastside
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
  • South Dakota
    • Aberdeen, South Dakota, United States, 57401
      • Avera Cancer Institute-Aberdeen
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center Oncology Clinic
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center
    • Sioux Falls, South Dakota, United States, 57105
      • Avera McKennan Hospital and University Health Center
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Wellmont Holston Valley Hospital and Medical Center
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee - Knoxville
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee Health Science Center
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital / Huntsman Intermountain Cancer Center
    • Cedar City, Utah, United States, 84720
      • Sandra L Maxwell Cancer Center
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • 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
    • Berlin, Vermont, United States, 05602
      • Central Vermont Medical Center/National Life Cancer Treatment
    • Burlington, Vermont, United States, 05405
      • University of Vermont and State Agricultural College
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Norton, Virginia, United States, 24273
      • Southwest VA Regional Cancer Center
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
  • Washington
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98112
      • Kaiser Permanente Washington
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology PS
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Green Bay, Wisconsin, United States, 54303
      • Saint Vincent Hospital Cancer Center at Saint Mary's
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology Limited at Saint Mary's Hospital
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology at Saint Vincent Hospital
    • Janesville, Wisconsin, United States, 53548
      • Mercyhealth Hospital and Cancer Center - Janesville
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53717
      • Dean Hematology and Oncology Clinic
    • Manitowoc, Wisconsin, United States, 54221
      • Holy Family Memorial Hospital
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Oconto Falls, Wisconsin, United States, 54154
      • Saint Vincent Hospital Cancer Center at Oconto Falls
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology - Sturgeon Bay
  • 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
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologic, pathologic or cytologic diagnosis of cancer of the female breast in either primary or metastatic setting; histological documentation of metastatic/recurrent disease is not required if there is unequivocal clinical evidence for recurrence
• Stage IV breast cancer (using American Joint Committee on Cancer [AJCC] criteria, 6th edition), or locally advanced (stage III) breast cancer not considered amenable to curative therapy
• Patients with symptomatic brain metastases or other symptomatic central nervous system (CNS) metastases are not eligible for the study; no screening studies are required among asymptomatic patients; patients with previously treated brain metastases, who are free of symptoms referable to CNS disease and who are > 3 months from treatment for brain metastases are eligible
• Tumors (as determined on pathology from either primary or metastatic sites) must be potentially sensitive to endocrine therapy, defined as expressing estrogen receptor (ER) and/or progesterone receptor (PgR) as determined immunohistochemical methods according to the local institution's standard protocol, >= 1% cells will be considered to be positive

• The protocol has been amended to permit tumors with any HER2 status, though a determination of HER2 status must have been made; patients will be considered to be eligible if HER2 expression is documented by one of the following methods:

  • Immunohistochemistry (IHC) 0 (i.e., negative), 1+, 2+, or 3+ levels of expression, or
  • Gene amplification (fluorescent in situ hybridization [FISH]) positive or negative

• Patients must have at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2.0 cm with conventional techniques or as >= 1.0 cm with spiral computed tomography (CT) scan

  • Exception: Patients with lytic or blastic bone metastases as their only site of disease will be eligible for the study even though these patients are not considered to have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria; these patients will be evaluable for time to progression, but not response
  • Patients with all other lesions, including small lesions (longest diameter < 2.0 cm with conventional techniques or < 1.0 cm with spiral CT scan) and truly non-measurable lesions including those listed below are not eligible

  • Lesions that are considered non-measurable include the following:

    • Bone lesions (women with bone lesions will be eligible as described above)
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Inflammatory breast cancer
    • Lymphangitis cutis/pulmonitis
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions

• Patients must have had one or two prior endocrine treatments for breast cancer in either the adjuvant or metastatic setting, exclusive of treatment-related amenorrhea or ovarian suppression; sequential use of two different third-generation aromatase inhibitors is considered "one" treatment; it is not required that tumors be resistant to such treatments; for example:

  • A patient with de novo metastatic breast cancer who had never received endocrine therapy is not eligible;
  • A patient who received adjuvant tamoxifen and subsequent therapy with an aromatase inhibitor (adjuvant or metastatic) is eligible;
  • A patient who received an aromatase inhibitor in either the adjuvant or metastatic setting, and who discontinued therapy after several months because of side effects, is eligible;
  • A patient who received an aromatase inhibitor in the adjuvant setting is eligible, regardless of whether they did or did not receive tamoxifen at some point;
  • A patient who received adjuvant tamoxifen, and subsequently a nonsteroidal aromatase inhibitor and a steroidal aromatase inhibitor for advanced breast cancer in the adjuvant or metastatic setting is eligible;
  • A patient who received adjuvant tamoxifen, and then a nonsteroidal aromatase inhibitor and subsequently megesterol acetate for advanced breast cancer is not eligible
• Tumors potentially sensitive to endocrine therapy, defined as >= 3 months of prior endocrine therapy without disease progression in the adjuvant or metastatic setting
• Patients must have had prior treatment in either the adjuvant or metastatic setting with a commercially available third-generation aromatase inhibitor (i.e. anastrozole, exemestane, or letrozole); it is not required that tumors be resistant to such therapies
• Patients may have received up to one prior chemotherapy regimen for stage IV breast cancer; prior chemotherapy in the adjuvant and/or neoadjuvant setting is permitted; patients must have finished chemotherapy at least 1 week prior to starting protocol based treatment
• Patients may have received prior trastuzumab therapy for stage IV breast cancer, in combination with up to one chemotherapy and/or endocrine therapy regimen, but that must have concluded at least 3 weeks prior to starting protocol-based therapy; prior trastuzumab therapy in the adjuvant and/or neoadjuvant setting is permitted, but must have concluded at least 3 weeks prior to starting protocol-based therapy
• Prior therapy with commercially available inhibitor of EGFR (including but not limited to gefitinib, erlotinib, lapatinib or cetuximab) or experimental inhibitors of EGFR is prohibited
• Patients may have initiated bisphosphonate therapy prior to study entry; such patients will have bone lesions considered evaluable for progression but not for response
• Prior fulvestrant therapy is prohibited
• Patients receiving a gonadotropin-releasing hormone (GnRH) agonist for ovarian suppression must remain on such therapy throughout the course of protocol treatment; patients must discontinue other endocrine treatments, including systemic hormone-replacement therapy and intravaginal estrogens prior to study entry; patients must have concluded radiation therapy prior to study entry; patients must be at least 1 week from prior chemotherapy or 3 weeks from prior trastuzumab therapy, with adequate recovery of bone marrow function and performance status

• Patients must be postmenopausal women, defined as a woman fulfilling any of the following criteria:

  • Age >= 60 years; or
  • Age >= 45 years with an intact uterus and amenorrhea for 12 months or more; or
  • History of bilateral oophorectomy; or
  • Follicle stimulating hormone (FSH) levels within postmenopausal range according to the ranges established by the testing facility; or
  • Treatment with a GnRH agonist for ovarian suppression for at least 3 consecutive months prior to study registration, and remaining on such therapy throughout the course of protocol treatment
  • Women who are pregnant or nursing are not eligible for the study; clinicians should advise patients that there are no data for the safety of lapatinib or fulvestrant among pregnant patients, nor data on the impact of these agents on fertility or pregnancy
• Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-2
• Absence of pending visceral crisis, in the opinion of the treating physician
• Absence of acquired or inherited bleeding disorder
• Absence of need for therapeutic systemic anticoagulation (defined as maintaining international normalized ratio [INR] > 1.6); patients may take low-dose warfarin or aspirin (or equivalent) for maintenance of central venous catheter patency
• Granulocytes >= 1,000/μl
• Platelet count >= 100,000/μl
• Creatinine =< 2 mg/dl
• Total bilirubin =< 1.5 x upper limits of normal (ULN) unless due to Gilbert's syndrome
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN without liver metastases; =< 5 x ULN with liver metastases
• INR =< 1.6
• Left ventricular ejection fraction (LVEF) within institutional limits of normal

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (lapatinib); Patients receive lapatinib ditosylate PO QD on days 1-28 and fulvestrant IM on days 1 and 15 of course 1 and on day 1 of each subsequent course. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Lapatinib Ditosylate; Given PO; Other Names: Tykerb; Drug: Fulvestrant; Given IM; Other Names: Faslodex; Faslodex(ICI 182,780); ICI 182,780; ICI 182780; ZD9238
Placebo Comparator: Arm II (placebo); Patients receive placebo PO QD on days 1-28 and fulvestrant as in Arm I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Placebo Administration; Given PO; Drug: Fulvestrant; Given IM; Other Names: Faslodex; Faslodex(ICI 182,780); ICI 182,780; ICI 182780; ZD9238

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	PFS was defined as the interval from study entry until disease progression or death resulting from any cause, which ever occurred first. Progression is defined as a 20% increase in the sum of longest diameter of target lesions (per RECIST criteria).	Interval from randomization until disease progression or death, whichever occurs first, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Tumor Response Rate	Response was defined by the Response Evaluation Criteria in Solid Tumors (RECIST). A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm.	Up to 5 years
Overall Survival (OS)	Overall survival was measured as the interval from study entry until death, from any cause, or last contact.	Study entry to death or last follow-up, up to 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival for Participants With HER2-negative Tumors	PFS was defined as the interval from study entry until disease progression or death resulting from any cause, which ever occurred first.	Up to 5 years
Progression-free Survival for Participants With HER2-positive Tumors	PFS was defined as the interval from study entry until disease progression or death resulting from any cause, whichever occurred first.	Up to 5 years
Objective Tumor Response Rate for Participants With HER2-negative Tumors	Response was defined by the RECIST. A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm.	Up to 5 years
Objective Tumor Response Rate for Participants With HER2-positive Tumors	Response was defined by the RECIST. A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm.	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Harold J Burstein, Alliance for Clinical Trials in Oncology

Publications and helpful links

General Publications

• Burstein HJ, Cirrincione CT, Barry WT, Chew HK, Tolaney SM, Lake DE, Ma C, Blackwell KL, Winer EP, Hudis CA. Endocrine therapy with or without inhibition of epidermal growth factor receptor and human epidermal growth factor receptor 2: a randomized, double-blind, placebo-controlled phase III trial of fulvestrant with or without lapatinib for postmenopausal women with hormone receptor-positive advanced breast cancer-CALGB 40302 (Alliance). J Clin Oncol. 2014 Dec 10;32(35):3959-66. doi: 10.1200/JCO.2014.56.7941. Epub 2014 Oct 27.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2006
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 2, 2014

Study Registration Dates

• First Submitted: October 18, 2006
• First Submitted That Met QC Criteria: October 18, 2006
• First Posted (Estimate): October 19, 2006

Study Record Updates

• Last Update Posted (Actual): December 20, 2019
• Last Update Submitted That Met QC Criteria: December 9, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Breast Diseases; Breast Neoplasms; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant; Lapatinib
• Other Study ID Numbers: NCI-2009-00475 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180821 (U.S. NIH Grant/Contract); U10CA031946 (U.S. NIH Grant/Contract); CDR0000510452; CALGB-40302 (Other Identifier: CTEP)