Bevacizumab in Treating Patients With Metastatic Breast Cancer That Overexpresses HER-2/NEU

A Randomized Phase III Double-Blind Placebo-Controlled Trial of First-Line Chemotherapy and Trastuzumab With or Without Bevacizumab for Patients With HER-2/NEU Over-Expressing Metastatic Breast Cancer

This randomized phase III trial studies first-line chemotherapy and trastuzumab to compare how well they work when given with or without bevacizumab in treating patients with breast cancer that overexpresses human epidermal growth factor receptor 2 (HER-2/NEU) and has spread to other areas of the body. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab and bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of breast cancer by blocking the growth of new blood vessels necessary for tumor growth. It is not yet known whether giving first-line chemotherapy together with trastuzumab is more effective with or without bevacizumab in treating patients with metastatic breast cancer that overexpresses HER-2/NEU.

Study Overview

• Status: Terminated
• Conditions: Breast Carcinoma; Stage IV Breast Cancer; Recurrent Breast Carcinoma
• Intervention / Treatment: Drug: Carboplatin; Biological: Trastuzumab; Drug: Paclitaxel; Biological: Bevacizumab; Other: Placebo

Detailed Description

PRIMARY OBJECTIVES:

I. Evaluate efficacy of the addition of bevacizumab in patients eligible for first-line trastuzumab with chemotherapy for HER-2/NEU overexpressing metastatic breast cancer, by assessing the progression-free survival (PFS) after initiation of combination therapy.

SECONDARY OBJECTIVES:

I. Evaluate response rates (RR) in patients with measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST]), when applicable.

II. Evaluate overall survival (OS).

III. Evaluate the proportion of progression-free at 6 months.

IV. Compare the toxicity of chemotherapy/trastuzumab to that of chemotherapy/ trastuzumab in combination with bevacizumab.

V. Evaluate left ventricular ejection fraction (LVEF) decline and clinical congestive heart failure (CHF).

EXPLORATORY OBJECTIVES:

I. Compare breast cancer symptoms and treatment related symptoms between patients receiving chemotherapy and trastuzumab with or without bevacizumab.

II. Evaluate whether PFS correlates with vascular endothelial growth factor (VEGF) levels in breast tumor tissue.

III. Analysis of circulating tumor cells and circulating endothelial cells (CEC).

1. Serially enumerate circulating tumor cells (CTC) and CEC in patients on study and determine whether: the number of CTC and CEC decrease in responding patients; the extent of CTC and CEC decrease is greater in the experimental arm, Arm B versus the control arm, Arm A; enumeration of CTC and CEC in responding patients correlate with progression free survival (PFS).
2. Perform an exploratory analysis of phosphorylation status of v-akt murine thymoma viral oncogene homolog (akt)-2 in circulating tumor cells.
3. Perform an exploratory analysis of reverse transcriptase (RT)-polymerase chain reaction (PCR) of CTC messenger ribonucleic acid (mRNA) to determine whether change in expression of selected downstream targets of bevacizumab therapy can serve as pharmacodynamic or surrogate markers of bevacizumab targeting and modulation.

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

ARM A:

INDUCTION THERAPY: Patients receive trastuzumab intravenously (IV) over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

ARM B:

INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: 489 patients

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Memorial Hospital
  • California
    • 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
    • Hayward, California, United States, 94545
      • Saint Rose Hospital
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Marysville, California, United States, 95901
      • Fremont - Rideout Cancer Center
    • Monterey, California, United States, 93940
      • Community Hospital of Monterey Peninsula
    • Mountain View, California, United States, 94040
      • El Camino Hospital
    • 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
    • Pomona, California, United States, 91767
      • Pomona Valley Hospital Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • San Pablo, California, United States, 94806
      • Doctors Medical Center- JC Robinson Regional 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
    • 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, 80222
      • Colorado Cancer Research Program NCORP
    • 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
      • SCL Health Lutheran Medical Center
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology and Oncology Associates
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
    • Atlanta, Georgia, United States, 30322
      • Emory University/Winship Cancer Institute
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Savannah, Georgia, United States, 31404
      • Memorial University Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
  • Idaho
    • Pocatello, Idaho, United States, 83201
      • Portneuf Medical Center
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Berwyn, Illinois, United States, 60402
      • MacNeal Hospital and Cancer Center
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Bloomington, Illinois, United States, 61701
      • Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Canton, Illinois, United States, 61520
      • Graham Hospital Association
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60611
      • Hematology and Oncology Associates
    • Chicago, Illinois, United States, 60612-3785
      • John H Stroger Jr Hospital of Cook County
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Heartland Cancer Research NCORP
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Eureka, Illinois, United States, 61530
      • Eureka Hospital
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare Galesburg
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Cottage
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Havana, Illinois, United States, 62644
      • Illinois CancerCare-Havana
    • Highland Park, Illinois, United States, 60035
      • Hematology Oncology Associates of Illinois-Highland Park
    • Hinsdale, Illinois, United States, 60521
      • Hinsdale Hematology Oncology Associates Incorporated
    • Hopedale, Illinois, United States, 61747
      • Hopedale Medical Complex - Hospital
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates Limited
    • Joliet, Illinois, United States, 60432
      • Midwest Center for Hematology Oncology
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Libertyville, Illinois, United States, 60048
      • NorthShore Hematology Oncology-Libertyville
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Moline, Illinois, United States, 61265
      • Garneau, Stewart C MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Porubcin, Michael MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Spector, David MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Sharis, Christine M MD (UIA Investigator)
    • Moline, Illinois, United States, 61265
      • Stoffel, Thomas J MD (UIA Investigator)
    • Monmouth, Illinois, United States, 61462
      • Illinois CancerCare-Monmouth
    • Monmouth, Illinois, United States, 61462
      • Holy Family Medical Center
    • Naperville, Illinois, United States, 60540
      • Edward Hospital/Cancer Center
    • Naperville, Illinois, United States, 60563
      • DuPage Medical Group-Ogden
    • Niles, Illinois, United States, 60714
      • Illinois Cancer Specialists-Niles
    • Normal, Illinois, United States, 61761
      • Community Cancer Center Foundation
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Illinois CancerCare-Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Ottawa, Illinois, United States, 61350
      • Ottawa Regional Hospital and Healthcare Center
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Pekin, Illinois, United States, 61554
      • 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
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Peru, Illinois, United States, 61354
      • Illinois Valley Hospital
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Skokie, Illinois, United States, 60076
      • Hematology Oncology Associates of Illinois - Skokie
    • Spring Valley, Illinois, United States, 61362
      • Saint Margaret's Hospital
    • Spring Valley, Illinois, United States, 61362
      • Illinois CancerCare-Spring Valley
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • Carle Clinic-Urbana Main
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • Franciscan St. Francis Health-Beech Grove
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Sidney and Lois Eskenazi Hospital
    • Indianapolis, Indiana, United States, 46260
      • Saint Vincent Hospital and Health Care Center
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Lafayette, Indiana, United States, 47904
      • IU Health Arnett Cancer Care
    • 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 Hospital and Health Care Services
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46617
      • South Bend Clinic
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium CCOP
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC-William R Bliss Cancer Center
    • Bettendorf, Iowa, United States, 52722
      • Constantinou, Costas L MD (UIA Investigator)
    • Davenport, Iowa, United States, 52803
      • Genesis Medical Center - East Campus
    • Davenport, Iowa, United States, 52804
      • Genesis Medical Center - West Campus
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50309
      • Iowa-Wide Oncology Research Coalition NCORP
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates-Laurel
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
    • Sioux City, Iowa, United States, 51104
      • Saint Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center-Sioux City
    • Waterloo, Iowa, United States, 50702
      • Covenant 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
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Topeka, Kansas, United States, 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
      • Wichita NCI Community Oncology Research Program
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Main Office
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • 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
      • Louisiana State University Health Science Center
    • New Orleans, Louisiana, United States, 70112
      • Interim LSU Public Hospital
  • 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
    • Easton, Maryland, United States, 21601
      • The Memorial Hospital at Easton
    • Easton, Maryland, United States, 21601
      • Memorial Hospital at Easton - Shore Regional Cancer 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 CCOP
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital and Medical Center
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Escanaba, Michigan, United States, 49431
      • Green Bay Oncology - Escanaba
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Flint, Michigan, United States, 48532
      • Genesys Regional Medical Center-West Flint Campus
    • 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
      • Toledo Clinic Cancer Centers-Monroe
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Saint Joseph Mercy Port Huron
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • 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 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
    • 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 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
    • Woodbury, Minnesota, United States, 55125
      • Woodwinds Health Campus
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology and Hematology PA-Woodbury
  • Missouri
    • Cape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Hospital
    • Jefferson City, Missouri, United States, 65101
      • Capital Regional Medical Center
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital-Joplin
    • 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
      • Center for Cancer Care and Research
    • Springfield, Missouri, United States, 65804
      • Cancer Research for the Ozarks NCORP
    • 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, 59102
      • Frontier Cancer Center and Blood Institute-Billings
    • Billings, Montana, United States, 59107
      • Billings Clinic Cancer Center
    • Billings, Montana, United States, 59101
      • Montana Cancer Consortium NCORP
    • 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
      • CHI Health Good Samaritan
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03802
      • Portsmouth Regional Hospital
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Summit, New Jersey, United States, 07902
      • Overlook Hospital
    • Vineland, New Jersey, United States, 08360
      • Inspira Medical Center Vineland
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College of Medicine
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center - Moses Campus
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Middletown, New York, United States, 10940
      • Orange Regional Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14623
      • Interlakes Foundation Inc-Rochester
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital-Memorial Campus
    • Fayetteville, North Carolina, United States, 28304
      • Cape Fear Valley Health System
    • Gastonia, North Carolina, United States, 28054
      • Gaston Memorial Hospital
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic
    • Bismarck, North Dakota, United States, 58501
      • Saint Alexius Medical Center
  • Ohio
    • Bellefontaine, Ohio, United States, 43311
      • Mary Rutan Hospital
    • Bowling Green, Ohio, United States, 43402
      • Toledo Clinic Cancer Centers-Bowling Green
    • Canton, Ohio, United States, 44708
      • Mercy Medical Center
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Clyde, Ohio, United States, 43410
      • North Coast Cancer Care-Clyde
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Columbus, Ohio, United States, 43215
      • Columbus NCI Community Oncology Research Program
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Health Center
    • Dayton, Ohio, United States, 45420
      • Dayton NCI Community Oncology Research Program
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45428
      • Veteran Affairs Medical Center
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Elyria, Ohio, United States, 44035
      • Hematology Oncology Center Incorporated
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Maumee, Ohio, United States, 43537
      • Toledo Clinic Cancer Centers-Maumee
    • Maumee, Ohio, United States, 43537
      • Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
    • Maumee, Ohio, United States, 43537
      • Saint Luke's Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Oregon, Ohio, United States, 43616
      • Saint Charles Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic Cancer Centers-Oregon
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • 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
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System Cancer Care Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Cancer Care Associates
  • Oregon
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
    • Portland, Oregon, United States, 97213
      • Western Oncology Research Consortium
    • Portland, Oregon, United States, 97216
      • Adventist Medical Center
  • Pennsylvania
    • Doylestown, Pennsylvania, United States, 18901
      • Doylestown Hospital
    • Lancaster, Pennsylvania, United States, 17604
      • Lancaster General Hospital
    • Pottstown, Pennsylvania, United States, 19464
      • Pottstown Memorial Medical Center
    • Reading, Pennsylvania, United States, 19605
      • Penn State Health Saint Joseph Medical Center
    • Sellersville, Pennsylvania, United States, 18960
      • Grand View Hospital
  • Rhode Island
    • Cranston, Rhode Island, United States, 02920
      • Hematology and Oncology Associates of Rhode Island Inc
    • Warwick, Rhode Island, United States, 02886
      • Kent County Hospital
  • South Dakota
    • Aberdeen, South Dakota, United States, 57401
      • Avera Saint Luke's Hospital and Cancer Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Medical Center
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee Health Science Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Dallas, Texas, United States, 75390
      • Clements University Hospital
    • Dallas, Texas, United States, 75235
      • Zale Lipshy University Hospital
    • Temple, Texas, United States, 76508
      • Scott and White Memorial Hospital
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • 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
      • Kadlec Clinic Hematology and Oncology
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • 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
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Charleston
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Healthcare
    • Parkersburg, West Virginia, United States, 26101
      • Camden-Clark Memorial Hospital
  • Wisconsin
    • Antigo, Wisconsin, United States, 54409
      • Langlade Hospital and Cancer Center
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Clinic Cancer Center at Sacred Heart
    • Eau Claire, Wisconsin, United States, 54701
      • Sacred Heart Hospital
    • 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
    • Johnson Creek, Wisconsin, United States, 53038
      • UW Cancer Center Johnson Creek
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Madison, Wisconsin, United States, 53717
      • Dean Hematology and Oncology Clinic
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Marshfield, Wisconsin, United States, 54449
      • Saint Joseph's Hospital
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology - Oconto Falls
    • Rhinelander, Wisconsin, United States, 54501
      • Marshfield Clinic at James Beck Cancer Center
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Clinic-Rice Lake Center
    • Stevens Point, Wisconsin, United States, 54481
      • Saint Michael's Hospital
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology - Sturgeon Bay
    • Weston, Wisconsin, United States, 54476
      • Diagnostic and Treatment Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Marshfield Clinic - Wisconsin Rapids Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Aspirus UW Cancer Center
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed breast cancer that overexpresses HER-2/NEU with evidence of metastatic disease and/or chest wall recurrence prior to randomization

• HER-2/NEU overexpression is defined as 3+ HER-2 positivity as measured by immunohistochemistry OR HER-2 gene amplification as measured by fluorescent in situ hybridization (FISH, e.g. Vysis), per American Society of Clinical Oncology guidelines

  • NOTE: representative diagnostic tissue must be submitted for central diagnostic review for confirmation of HER-2/NEU overexpression within two weeks following patient randomization
• Evaluable (measurable or non-measurable) disease is allowed if confirmed within 4 weeks prior to randomization
• Prior endocrine treatment in the adjuvant or metastatic setting is allowed, provided last dose given >= 2 weeks prior to randomization
• Radiation therapy is allowed provided last dose is given >= 3 weeks prior to randomization
• Adjuvant trastuzumab therapy for breast cancer is allowed provided last dose was given >= 12 months prior to diagnosis of recurrence
• Adjuvant or neoadjuvant taxane therapy for breast cancer is allowed provided last dose was given >= 12 months prior to diagnosis of recurrence
• Adjuvant or neoadjuvant therapy with lapatinib is allowed provided last dose is given >= 4 weeks prior to diagnosis of recurrence
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count >= 1,000/mm^3
• Platelet count >= 100,000/mm^3
• Total bilirubin =< 1.5 mg/dL
• Aspartate aminotransferase (AST) =< 2 times upper limit of normal (ULN) (=< 5 times normal in patients with known liver involvement)
• Serum creatinine =< 1.5 mg/dL
• Urine protein: creatinine ratio =< 0.5 OR 24-hour urine protein < 1000 mg
• International normalized ratio (INR) =< 1.5 X ULN
• Partial thromboplastin time (PTT) =< 1.5 X ULN
• Multi gated acquisition scan (MUGA) scan or echocardiogram (ECHO) within 6 weeks prior to randomization with an left ventricular ejection fraction (LVEF) above the institutional lower limit of normal
• Patients must be able to understand and provide signed and dated written informed consent
• Major surgical procedure within 4 weeks prior to randomization is not allowed (except for non-operative biopsy, which would not be considered major surgery); treatment can not begin until seven (7) days after placement of a vascular access device
• Women must not be pregnant or breastfeeding; all females of childbearing potential must have a blood or urine test within 2 weeks prior to randomization to rule out pregnancy; women of childbearing potential and sexually active males must use an accepted and effective method of contraception

• Patients on full-dose anticoagulants (e.g., warfarin) with PT/INR > 1.5 may be eligible provided that both of the following criteria are met:

  • The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
  • The patient has not active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
• Patients with a concurrent active malignancy except carcinoma in situ of the cervix or non-melanoma skin cancers (unless disease-free for at least 5 years at study entry) are not allowed

Exclusion Criteria:

• Prior chemotherapy, trastuzumab, or bevacizumab for metastatic breast cancer
• Patients who have had a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 640 mg/m^2 in the adjuvant or neo-adjuvant setting at any time
• Patients with grade 2-4 neuropathy
• Patients with a history or radiologic evidence of central nervous system (CNS) disease
• Patients have a current non-healing wound or fracture
• Patients have a hypersensitivity to paclitaxel or drugs using the vehicle Cremophor, Chinese hamster ovary cell products or other recombinant human antibodies
• Patients have a serious medical or psychiatric illness that would prevent ability to safely participate or provide informed consent
• Patients using any of the following drugs known to inhibit platelet function are not eligible: dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and cilostazol (Pletal)

• Clinically significant cardiovascular disease, including:

  • History of cerebrovascular (CVA) within 6 months
  • Uncontrolled hypertension
  • Myocardial infarction or unstable angina within 6 months
  • New York Heart Association class II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris
  • Clinically significant peripheral vascular disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (chemotherapy and placebo); INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Carboplatin; Given IV; Other Names: CBDCA; JM-8; Paraplatin; NSC-241240; Biological: Trastuzumab; Given IV; Other Names: Herceptin; Anti-HER2 Monoclonal Antibody; Drug: Paclitaxel; Given IV; Other Names: Taxol; NSC 125973; Other: Placebo; Given IV; Other Names: placebo therapy; sham therapy
Experimental: Arm B (chemotherapy and bevacizumab); INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Carboplatin; Given IV; Other Names: CBDCA; JM-8; Paraplatin; NSC-241240; Biological: Trastuzumab; Given IV; Other Names: Herceptin; Anti-HER2 Monoclonal Antibody; Drug: Paclitaxel; Given IV; Other Names: Taxol; NSC 125973; Biological: Bevacizumab; Given IV; Other Names: Avastin; Anti-VEGF Humanized Monoclonal Antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival (PFS) was defined as time from date of randomization to first disease progression, new second breast primaries, or to death from any cause, whichever occurred first, otherwise cases were censored at date last documented to be free of progression. Disease progression was defined using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier method was used to estimate the median PFS.	assessed every 3 months for patients within 2 years of registration, every 6 months for patients 3-5 years from registration and then yearly for up to10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival (OS) is defined as the time from randomization until death (event), or censored at last date known alive. Kaplan-Meier method was used to estimate the median OS.	assessed every 3 months for patients within 2 years of registration, every 6 months for patients 3-5 years from registration and then yearly for up to10 years
Proportion of Progression-free at 6 Months	Disease progression was defined using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Proportion of progression-free at 6 months was calculated using the Kaplan-Meier method.	assessed at baseline, at 3 and 6 months after study entry
Overall Response Rate	Overall response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all randomized patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and/or persistence of one or more non-target lesion(s).	assessed at baseline, every 12 weeks while on treatment, then very 3 months if patient is <2 years from study entry, every 6 months if 2-5 years from study entry, and annually if 6-10 years from study entry until disease progression
Number of Patients Experiencing Congestive Heart Failure	Clinical congestive heart failure (CHF) was assessed using Left Ventricular Ejection Fraction (LVEF) and symptom information via the Cardiac Toxicity Form as well as symptom information collected via the Adverse Event Form. Clinical CHF was defined as symptomatic decline in LVEF to below the lower limit of normal (LLN) or symptomatic diastolic dysfunction.	assessed every 3 months while on treatment and at 3 months post treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fatigue Level Between Baseline and Cycle 6 Induction	Fatigue level was measured using Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue subscale. Participants indicated their level of fatigue across 13 items, each item on a 5-point Likert scale ranging from 0 (not at all) to 4(very much). Total score per patient was calculated by taking the reverse of each item (unless specified not to), taking the sum of those items, multiplying the sum by the number of items in the scale, and then dividing that number by the number of answered items. Total score ranged from 0 to 52 with higher scores representing less fatigue.	assessed at baseline and at cycle 6 induction prior to starting maintenance therapy
Change in FACT/NCCN Breast Symptom Index (FBSI) Between Baseline and Cycle 6 Induction	Participants indicated their level of breast symptoms across 8 items using the Functional Assessment of Cancer Therapy/National Comprehensive Cancer Network (FACT/NCCN) FBSI scale, each item on a 5-point Likert scale ranging from 0 (not at all) to 4(very much). Total score per patient, ranged from 0 to 32 with higher scores representing fewer symptoms.	assessed at baseline and at cycle 6 induction prior to starting maintenance therapy
Change in Neurotoxicity Level Between Baseline and Cycle 6 Induction	Participants indicated their level of neurotoxicity symptoms across 4 items using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) scale, each item on a 5-point Likert scale ranging from 0 (not at all) to 4(very much). Total score per patient ranged from 0 to 16 with higher scores representing fewer neurotoxic symptoms.	assessed at baseline and at cycle 6 induction prior to starting maintenance therapy
Change in Level of Experiencing Side Effects Between Baseline and Cycle 6 Induction	Participants indicated their level of experiencing side effects across 1 item (Functional Assessment of Cancer Therapy [FACT] item G5) on a 5-point Likert scale ranging from 0 (not at all) to 4(very much). Total score per patient, ranged from 0 to 4 with a higher score representing better quality of life (QOL).	assessed at baseline and at cycle 6 induction prior to starting maintenance therapy
Number of Circulating Tumor Cells at Baseline	Number of circulating tumor cells per 7.5mL blood were counted prior to starting protocol therapy	assessed at baseline prior to starting protocol therapy
VEGF Levels in Breast Tumor by Immunohistochemistry Assay (Tumor Sample Has Not Been Analyzed Yet, no Results Could be Reported)	Tissue sections from the primary or metastatic paraffin blocks were subjected to VEGF immunohistochemistry (IHC). The VEGF cytoplasmic staining intensity was evaluated semiquantitavely using a classification from 0 to 3, with 0 representing lack of staining, 1 = low staining intensity, 2 = intermediate staining intensity and 3 = strong staining intensity. The fraction of positively staining cells will be determined as well (0 = lack of staining, 1 ≤ 1% cell staining, 2 = 1 - 10% cell staining, 3 = 10 - 50% cell staining, 4 = 50 - 90% cells staining and 5 ≤ 90% cells staining) (48). Staining intensity score zero and fraction of positively staining cells of ≤ 1% (scores zero and 1) will be considered as absence of staining and therefore negative overexpression of VEGF.	assessed at baseline

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: August 24, 2007
• First Submitted That Met QC Criteria: August 24, 2007
• First Posted (Estimate): August 27, 2007

Study Record Updates

• Last Update Posted (Estimate): February 6, 2017
• Last Update Submitted That Met QC Criteria: December 12, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Bevacizumab; Metastatic Breast Cancer; Trastuzumab; HER2/NEU
• 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; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Paclitaxel; Trastuzumab; Antibodies; Immunoglobulins; Bevacizumab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological
• Other Study ID Numbers: NCI-2009-00504 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180794 (U.S. NIH Grant/Contract); U10CA023318 (U.S. NIH Grant/Contract); E1105 (Other Identifier: ECOG-ACRIN Cancer Research Group)

Plan for Individual participant data (IPD)

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