Whole-Brain Radiation Therapy or Stereotactic Radiosurgery With or Without Lapatinib Ditosylate in Treating Patients With Brain Metastasis From HER2-Positive Breast Cancer

Phase II Randomized Study of Whole Brain Radiotherapy/Stereotactic Radiosurgery in Combination With Concurrent Lapatinib in Patients With Brain Metastasis From HER2-Positive Breast Cancer - A Collaborative Study of NRG Oncology and KROG

This randomized phase II trial studies how well whole-brain radiation therapy or stereotactic radiosurgery with or without lapatinib ditosylate works in treating patients with breast cancer that has too many of a protein called human epidermal growth factor receptor 2 (HER2) on its cells and has spread to the brain. Radiation therapy uses high energy x rays to kill tumor cells and shrink tumors. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether whole-brain radiation therapy or stereotactic radiosurgery together with lapatinib ditosylate is an effective treatment for brain metastasis from breast cancer.

Study Overview

• Status: Completed
• Conditions: Recurrent Breast Carcinoma; Invasive Breast Carcinoma; Metastatic Malignant Neoplasm in the Brain; Stage IV Breast Cancer AJCC v6 and v7; HER2-Positive Breast Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Radiation: Stereotactic Radiosurgery; Drug: Lapatinib Ditosylate; Radiation: Whole-Brain Radiotherapy

Detailed Description

PRIMARY OBJECTIVES:

I. To determine if there is a signal for an increase in complete response (CR) rate in the measurable brain metastases at 12 weeks post radiation therapy (RT) (whole brain or stereotactic radiosurgery [SRS]) as determined by magnetic-resonance imaging (MRI) scan of the brain, with the addition of lapatinib (lapatinib ditosylate) to whole-brain radiation therapy (WBRT)/SRS compared to WBRT/SRS alone.

SECONDARY OBJECTIVES:

I. To evaluate CR rate of the measurable brain metastases at 4 weeks post RT (WBRT/SRS) as determined by MRI scan of the brain, with the addition of lapatinib to WBRT/SRS compared to WBRT/SRS alone.

II. To evaluate objective response rate of measurable brain metastases at 4 and 12 weeks post RT (WBRT/SRS) as determined by MRI scan of the brain, with the addition of lapatinib to WBRT/SRS compared to WBRT/SRS alone.

III. To evaluate targeted lesion-specific objective response rate (CR + partial response [PR]) at 4 and 12 weeks post WBRT/SRS.

IV. To evaluate central nervous system (CNS) progressive disease outside the targeted measurable disease with addition of lapatinib to WBRT/SRS compared to WBRT/SRS alone.

V. To evaluate targeted lesion-specific progression at 4 and 12 weeks post WBRT/SRS.

VI. To evaluate treatment related adverse events when adding lapatinib to WBRT/SRS compared to WBRT/SRS alone.

VII. To evaluate overall CNS complete response: disappearance of all CNS target lesions sustained for at least 4 weeks; with no new lesions, no use of corticosteroids, and patient is stable or improved clinically, when adding lapatinib to WBRT/SRS compared to WBRT/SRS alone.

VIII. To evaluate overall CNS progressive disease (within or outside targeted measurable disease) with addition of lapatinib to WBRT/SRS compared to WBRT/SRS alone.

IX. To evaluate overall survival when adding lapatinib to WBRT/SRS compared to WBRT/SRS alone.

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

ARM A: Patients undergo WBRT 5 days a week for 3 weeks for a total of 15 treatments or SRS for 1 treatment.

ARM B: Patients undergo WBRT or SRS as in Arm A. Patients also receive lapatinib ditosylate orally (PO) once daily (QD) for 6 weeks.

After completion of study treatment, patients are followed up at 4 and 12 weeks and then every 12 weeks thereafter.

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University Health System-Severance Hospital
  • Seoul, Korea, Republic of, 06273
    • Gangnam Severance Hospital
  • Daegu
    • Dalseo-gu, Daegu, Korea, Republic of, 42601
      • Keimyung University-Dongsan Medical Center
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
      • National Cancer Center-Korea
  • Jeollanam-do
    • Hwasun-gun, Jeollanam-do, Korea, Republic of, 519-763
      • Chonnam National University Hwasun Hospital
  • Korea
    • Seoul, Korea, Korea, Republic of, 135-710
      • Samsung Medical Center
  • Kyeonggi-do
    • Seongnam City, Kyeonggi-do, Korea, Republic of, 463-707
      • Seoul National University Bundang Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
    • Birmingham, Alabama, United States, 35243
      • The Kirklin Clinic at Acton Road
    • Mobile, Alabama, United States, 36688
      • University of South Alabama Mitchell Cancer Institute
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Saint Joseph's Hospital and Medical Center
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center - Tucson
  • California
    • Auburn, California, United States, 95602
      • Sutter Auburn Faith Hospital
    • Auburn, California, United States, 95603
      • Sutter Cancer Centers Radiation Oncology Services-Auburn
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center-Herrick Campus
    • Burlingame, California, United States, 94010
      • Mills-Peninsula Medical Center
    • Cameron Park, California, United States, 95682
      • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    • Carmichael, California, United States, 95608
      • Mercy San Juan Medical Center
    • Davis, California, United States, 95616
      • Sutter Davis Hospital
    • Dublin, California, United States, 94568
      • Epic Care-Dublin
    • Emeryville, California, United States, 94608
      • Bay Area Breast Surgeons Inc
    • Emeryville, California, United States, 94608
      • Epic Care Partners in Cancer Care
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Modesto, California, United States, 95355
      • Memorial Medical Center
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Camino Division
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Gynecologic Oncology
    • Novato, California, United States, 94945
      • Sutter Cancer Research Consortium
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94609
      • Bay Area Tumor Institute
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
    • Palo Alto, California, United States, 94301
      • Palo Alto Medical Foundation Health Care
    • Roseville, California, United States, 95661
      • Sutter Cancer Centers Radiation Oncology Services-Roseville
    • Roseville, California, United States, 95661
      • Sutter Roseville Medical Center
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • Sacramento, California, United States, 95819
      • Mercy General Hospital Radiation Oncology Center
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center-Pacific Campus
    • Santa Cruz, California, United States, 95065
      • Palo Alto Medical Foundation-Santa Cruz
    • Santa Rosa, California, United States, 95403
      • Sutter Pacific Medical Foundation
    • Sunnyvale, California, United States, 94086
      • Palo Alto Medical Foundation-Sunnyvale
    • Vacaville, California, United States, 95687
      • Sutter Cancer Centers Radiation Oncology Services-Vacaville
    • Vallejo, California, United States, 94589
      • Sutter Solano Medical Center/Cancer Center
    • Walnut Creek, California, United States, 94597
      • Epic Care Cyberknife Center
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19713
      • Delaware Clinical and Laboratory Physicians PA
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants PA
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Newark, Delaware, United States, 19713
      • Christiana Gynecologic Oncology LLC
    • Rehoboth Beach, Delaware, United States, 19971
      • Beebe Health Campus
    • Seaford, Delaware, United States, 19973
      • TidalHealth Nanticoke / Allen Cancer Center
    • Wilmington, Delaware, United States, 19801
      • Christiana Care Health System-Wilmington Hospital
  • Florida
    • Deerfield Beach, Florida, United States, 33442
      • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Cumming, Georgia, United States, 30041
      • Northside Hospital-Forsyth
    • Fayetteville, Georgia, United States, 30214
      • Piedmont Fayette Hospital
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center-Gainesville
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Caldwell, Idaho, United States, 83605
      • Saint Alphonsus Cancer Care Center-Caldwell
    • Meridian, Idaho, United States, 83642
      • Idaho Urologic Institute-Meridian
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
    • Chicago, Illinois, United States, 60657
      • UChicago Medicine Comprehensive Cancer Center - Saint Joseph Hospital
    • Danville, Illinois, United States, 61832
      • Carle on Vermilion
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Elkhart, Indiana, United States, 46514
      • Michiana Hematology Oncology PC-Elkhart
    • Elkhart, Indiana, United States, 46514-2098
      • Elkhart Clinic
    • Fort Wayne, Indiana, United States, 46805
      • Parkview Hospital Randallia
    • Fort Wayne, Indiana, United States, 46845
      • Parkview Regional Medical Center
    • Fort Wayne, Indiana, United States, 46804
      • Radiation Oncology Associates PC
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Mishawaka, Indiana, United States, 46545
      • Memorial Regional Cancer Center Day Road
    • Mishawaka, Indiana, United States, 46545
      • Michiana Hematology Oncology PC-Mishawaka
    • Mishawaka, Indiana, United States, 46545
      • Saint Joseph Regional Medical Center-Mishawaka
    • Plymouth, Indiana, United States, 46563
      • Michiana Hematology Oncology PC-Plymouth
    • Richmond, Indiana, United States, 47374
      • Reid Health
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • Michiana Hematology Oncology PC-South Bend
    • South Bend, Indiana, United States, 46617
      • South Bend Clinic
    • Westville, Indiana, United States, 46391
      • Michiana Hematology Oncology PC-Westville
  • Iowa
    • Cedar Rapids, Iowa, United States, 52402
      • Saint Luke's Hospital
  • Kansas
    • Garden City, Kansas, United States, 67846
      • Central Care Cancer Center - Garden City
    • Great Bend, Kansas, United States, 67530
      • Central Care Cancer Center - Great Bend
    • Lenexa, Kansas, United States, 66219
      • Kansas Institute of Medicine Cancer and Blood Center
    • Lenexa, Kansas, United States, 66219
      • Minimally Invasive Surgery Hospital
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66213
      • Saint Luke's South Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Hospital Pavilion and Medical Campus
    • Louisville, Kentucky, United States, 40207
      • Norton Suburban Hospital and Medical Campus
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Bixby Medical Center
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Big Rapids, Michigan, United States, 49307
      • Spectrum Health Big Rapids Hospital
    • Brighton, Michigan, United States, 48114
      • Saint Joseph Mercy Brighton
    • Brownstown, Michigan, United States, 48183
      • Henry Ford Cancer Institute-Downriver
    • Canton, Michigan, United States, 48188
      • Saint Joseph Mercy Canton
    • Chelsea, Michigan, United States, 48118
      • Saint Joseph Mercy Chelsea
    • Clinton Township, Michigan, United States, 48038
      • Henry Ford Macomb Hospital-Clinton Township
    • Dearborn, Michigan, United States, 48124
      • Beaumont Hospital - Dearborn
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48236
      • Ascension Saint John Hospital
    • Escanaba, Michigan, United States, 49829
      • Green Bay Oncology - Escanaba
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Iron Mountain, Michigan, United States, 49801
      • Green Bay Oncology - Iron Mountain
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Medical Center
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital
    • Monroe, Michigan, United States, 48162
      • Toledo Clinic Cancer Centers-Monroe
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Niles, Michigan, United States, 49120
      • Lakeland Hospital Niles
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Pontiac, Michigan, United States, 48341
      • 21st Century Oncology-Pontiac
    • Port Huron, Michigan, United States, 48060
      • Lake Huron Medical Center
    • Saginaw, Michigan, United States, 48601
      • Ascension Saint Mary's Hospital
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center Saint Joseph
    • Saint Joseph, Michigan, United States, 49085
      • Marie Yeager Cancer Center
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
    • 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
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Maple Grove, Minnesota, United States, 55369
      • Fairview Clinics and Surgery Center Maple Grove
    • 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, 55454
      • Health Partners Inc
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
    • Pascagoula, Mississippi, United States, 39581
      • Singing River Hospital
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center - Bolivar
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • Independence, Missouri, United States, 64057
      • Centerpoint Medical Center LLC
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital Joplin
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Kansas City, Missouri, United States, 64118
      • Heartland Hematology and Oncology Associates Incorporated
    • Lee's Summit, Missouri, United States, 64086
      • Saint Luke's East - Lee's Summit
    • Liberty, Missouri, United States, 64068
      • Liberty Radiation Oncology Center
    • Rolla, Missouri, United States, 65401
      • Delbert Day Cancer Institute at PCRMC
    • Rolla, Missouri, United States, 65401
      • Mercy Clinic-Rolla-Cancer and Hematology
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • Saint Joseph, Missouri, United States, 64507
      • Saint Joseph Oncology Inc
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
    • Saint Louis, Missouri, United States, 63109
      • Saint Louis Cancer and Breast Institute-South City
    • Saint Louis, Missouri, United States, 63141
      • Saint Louis-Cape Girardeau CCOP
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
  • New Hampshire
    • Manchester, New Hampshire, United States, 03103
      • Elliot Hospital
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • Voorhees, New Jersey, United States, 08043
      • Virtua Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
    • Las Cruces, New Mexico, United States, 88011
      • Memorial Medical Center - Las Cruces
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Campus
    • Brooklyn, New York, United States, 11215
      • New York-Presbyterian/Brooklyn Methodist Hospital
    • 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
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14620
      • Highland Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Hendersonville, North Carolina, United States, 28792
      • AdventHealth Hendersonville
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
  • Ohio
    • Akron, Ohio, United States, 44307
      • Cleveland Clinic Akron General
    • Akron, Ohio, United States, 44304
      • Summa Health System - Akron Campus
    • Alliance, Ohio, United States, 44601
      • Radiation Oncology Center
    • Barberton, Ohio, United States, 44203
      • Summa Health System - Barberton Campus
    • Beachwood, Ohio, United States, 44122
      • UHHS-Chagrin Highlands Medical Center
    • Beachwood, Ohio, United States, 44122
      • Cleveland Clinic Cancer Center Beachwood
    • Bowling Green, Ohio, United States, 43402
      • Toledo Clinic Cancer Centers-Bowling Green
    • Canton, Ohio, United States, 44708
      • Cleveland Clinic Mercy Hospital
    • Centerville, Ohio, United States, 45459
      • Miami Valley Hospital South
    • Centerville, Ohio, United States, 45459
      • Dayton Physicians LLC-Miami Valley South
    • Chardon, Ohio, United States, 44024
      • Geauga Hospital
    • Cincinnati, Ohio, United States, 45236
      • Oncology Hematology Care Inc-Kenwood
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Dayton Physician LLC-Miami Valley Hospital North
    • Dayton, Ohio, United States, 45415
      • Miami Valley Hospital North
    • Elyria, Ohio, United States, 44035
      • Mercy Cancer Center-Elyria
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Findlay, Ohio, United States, 45840
      • Armes Family Cancer Center
    • Findlay, Ohio, United States, 45840
      • Orion Cancer Care
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Franklin, Ohio, United States, 45005
      • Dayton Physicians LLC-Atrium
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Greenville, Ohio, United States, 45331
      • Dayton Physicians LLC-Wayne
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center Independence
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Mansfield, Ohio, United States, 44906
      • Cleveland Clinic Cancer Center Mansfield
    • Maumee, Ohio, United States, 43537
      • Toledo Clinic Cancer Centers-Maumee
    • Maumee, Ohio, United States, 43537
      • Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Medina, Ohio, United States, 44256
      • Summa Health Medina Medical Center
    • Mentor, Ohio, United States, 44060
      • UH Seidman Cancer Center at Lake Health Mentor Campus
    • Middleburg Heights, Ohio, United States, 44130
      • UH Seidman Cancer Center at Southwest General Hospital
    • Oregon, Ohio, United States, 43616
      • Saint Charles Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic Cancer Centers-Oregon
    • Parma, Ohio, United States, 44129
      • University Hospitals Parma Medical Center
    • Ravenna, Ohio, United States, 44266
      • University Hospitals Portage Medical Center
    • Salem, Ohio, United States, 44460
      • UH Seidman Cancer Center at Salem Regional Medical Center
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • Springfield, Ohio, United States, 45504
      • Springfield Regional Cancer Center
    • Strongsville, Ohio, United States, 44136
      • Cleveland Clinic Cancer Center Strongsville
    • Sylvania, Ohio, United States, 43560
      • ProMedica Flower Hospital
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43608
      • Saint Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43623
      • Mercy Health - Saint Anne Hospital
    • 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
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Troy, Ohio, United States, 45373
      • Dayton Physicians LLC-Upper Valley
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
    • Westlake, Ohio, United States, 44145
      • UHHS-Westlake Medical Center
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic Wooster Family Health and Surgery Center
    • Wooster, Ohio, United States, 44691
      • Cancer Treatment Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at Saint Francis
    • Tulsa, Oklahoma, United States, 74146
      • Warren Clinic Oncology-Tulsa
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital and Medical Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Jefferson Abington Hospital
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Bethlehem, Pennsylvania, United States, 18017
      • Lehigh Valley Hospital - Muhlenberg
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Pocono Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Cancer Center
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Gaffney, South Carolina, United States, 29341
      • Gibbs Cancer Center-Gaffney
    • Greer, South Carolina, United States, 29651
      • Gibbs Cancer Center-Pelham
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
  • Texas
    • Lubbock, Texas, United States, 79410
      • Covenant Medical Center-Lakeside
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Vermont
    • Berlin, Vermont, United States, 05602
      • Central Vermont Medical Center/National Life Cancer Treatment
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
    • Burlington, Vermont, United States, 05405
      • University of Vermont and State Agricultural College
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology Inc
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
  • Washington
    • Vancouver, Washington, United States, 98686
      • Legacy Salmon Creek Hospital
  • West Virginia
    • Wheeling, West Virginia, United States, 26003
      • Wheeling Hospital/Schiffler Cancer Center
  • 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
    • Johnson Creek, Wisconsin, United States, 53038
      • UW Cancer Center Johnson Creek
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center
    • Manitowoc, Wisconsin, United States, 54221
      • Holy Family Memorial Hospital
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Mequon, Wisconsin, United States, 53097
      • Ascension Columbia Saint Mary's Hospital Ozaukee
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53211
      • Ascension Columbia Saint Mary's Hospital - Milwaukee
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin
    • Oconto Falls, Wisconsin, United States, 54154
      • Saint Vincent Hospital Cancer Center at Oconto Falls
    • Sturgeon Bay, Wisconsin, United States, 54235-1495
      • Saint Vincent Hospital Cancer Center at Sturgeon Bay
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology - Sturgeon Bay

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of invasive breast cancer
• HER2-overexpressing breast cancer (3+ staining by immunohistochemistry or HER2 gene amplification by fluorescent in situ hybridization [FISH] or silver in situ hybridization [SISH] >= 2.0)

• At least 1 measurable unirradiated parenchymal brain metastasis within 21 days prior to study entry; patients who are to undergo SRS must have no more than 10 brain metastases; there is no limit on number of brain metastases for WBRT; the minimum size as measured on T1-weighted gadolinium-enhanced MRI must be as follows according to the number of brain metastases:

  • For a single solitary lesion the size must be >= 10 mm
  • For 2 or more lesions, the size of at least 2 of the lesions must be >= 5 mm

  • Patients may also have the following provided the size requirements above are met:

    • Progressive parenchymal brain metastasis following stereotactic radiosurgery for 1-3 brain metastases, with at least 1 new measurable brain lesion
    • Progressive parenchymal brain metastasis following surgical resection of 1-3 brain metastases, with at least 1 measurable brain lesion
• History/physical examination within 21 days prior to study entry
• Karnofsky performance status >= 60 within 21 days prior to study entry
• Able to swallow and retain oral medication (note: for patients unable to swallow tablets, an oral suspension preparation is acceptable)
• Absolute neutrophil count (ANC) >= 1,200 cells/mm^3 (within 21 days prior to study entry)
• Platelets >= 70,000 cells/mm^3 (within 21 days prior to study entry)
• Hemoglobin >= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dL is acceptable) (within 21 days prior to study entry)
• Creatinine < 1.5 times institutional upper limit of normal (within 21 days prior to study entry)
• Bilirubin < 1.5 times institutional upper limit of normal (within 21 days prior to study entry)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 times institutional upper limit of normal with or without liver metastasis (within 21 days prior to study entry)
• Patient must provide study specific informed consent prior to study entry
• Women of childbearing potential must have a negative serum pregnancy test within 21 days prior to study entry
• Sexually active women of childbearing potential and sexually active men must practice adequate contraception during therapy and for 12 months after protocol treatment completion
• Prior lapatinib is allowed as long as the last dose received was > 21 days prior to study entry and provided the patient has not received it at any time after the diagnosis of brain metastasis

Exclusion Criteria:

• Prior WBRT
• Prior radiation therapy (RT) (any site) with concurrent lapatinib defined as 1 or more days on which the patient received both radiation therapy and lapatinib on the same day
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Prior invasive malignancy (except non-melanomatous skin cancer, curatively resected thyroid papillary carcinoma, and invasive and non-invasive cancers related to the breast cancer) unless disease free for a minimum of 3 years
• Leptomeningeal disease
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields except patients who have progressed following stereotactic radiosurgery for 1-3 brain metastases, with at least one new lesion

• Severe, active co-morbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study entry
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study entry
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; hepatic or biliary disease that is acute or currently active or that requires antiviral therapy (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)
  • History of left ventricular ejection fraction (LVEF) below institutional normal unless repeated and within institutional normal range within 90 days of study entry
• Grade 2 or greater rash of any cause at time of study entry
• Grade 2 or greater diarrhea of any cause at time of study entry

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (WBRT or SRS); Patients undergo WBRT 5 days a week for 3 weeks for a total of 15 treatments, or SRS for 1 treatment.	Other: Laboratory Biomarker Analysis; Correlative studies; Radiation: Stereotactic Radiosurgery; Undergo SRS; Other Names: Stereotactic External Beam Irradiation; stereotactic external-beam radiation therapy; Stereotactic Radiotherapy; stereotaxic radiation therapy; stereotaxic radiosurgery; Stereotactic Radiation Therapy; Radiation: Whole-Brain Radiotherapy; Undergo WBRT; Other Names: WBRT; whole-brain radiation therapy
Experimental: Arm B (lapatinib ditosylate, WBRT or SRS); Patients undergo WBRT or SRS as in Arm A. Patients also receive lapatinib ditosylate PO QD for 6 weeks.	Other: Laboratory Biomarker Analysis; Correlative studies; Radiation: Stereotactic Radiosurgery; Undergo SRS; Other Names: Stereotactic External Beam Irradiation; stereotactic external-beam radiation therapy; Stereotactic Radiotherapy; stereotaxic radiation therapy; stereotaxic radiosurgery; Stereotactic Radiation Therapy; Drug: Lapatinib Ditosylate; Given PO; Other Names: Tykerb; Radiation: Whole-Brain Radiotherapy; Undergo WBRT; Other Names: WBRT; whole-brain radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR) Rate in the Brain at 12 Weeks Post-radiation Therapy (RT) Using the RECIST 1.1 Criteria Based on Brain Magnetic Resonance Imaging (MRI)	The Response Evaluation Criteria in Solid Tumors (RECIST) criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Complete response is defined as the complete disappearance of all enhancing disease and off all steroids. Rate is calculated by dividing the number of patients with complete response by the number of analyzable patients.	Baseline and 12 weeks post RT (approximately 12 weeks from start of treatment if SRS and 15 if WBRT)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate in the Brain at 4 Weeks Post-RT Using the RECIST 1.1 Criteria Based on Brain MRI	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Complete response is defined as the complete disappearance of all enhancing disease and off all steroids. Rate is calculated by dividing the number of patients with complete response by the number of analyzable patients.	Baseline and 4 weeks post RT (approximately 4 weeks from start of treatment if SRS and 7 if WBRT)
Complete Response Rate in the Brain Using the World Health Organization (WHO)/Modified McDonald Criteria Based on Brain MRI	The WHO/modified McDonald Criteria evaluates changes in bidimensional tumor measurements. Complete response is defined as the complete disappearance of all enhancing disease and off all steroids. Rate is calculated by dividing the number of patients with complete response by the number of analyzable patients.	Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)
Objective Response Rate in the Brain Using the RECIST 1.1 Criteria Based on Brain MRI	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Objective response is defined as a complete or partial response. Complete response is defined as the complete disappearance of all enhancing disease and off all steroids. Partial response is defined as ≥ 30% reduction in the sum of diameters of up to 2 of the largest target lesions. Rate is calculated by dividing the number of patients with objective response by the number of analyzable patients.	Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)
Percentage of Participants With Progression in the Brain Outside the Targeted Measurable Disease Using the RECIST 1.1 Criteria Based on Brain MRI	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. CNS progressive disease outside the targeted measureable disease was determined by a retrospective central review of MRI scans by the study neuroradiology co-chair and is defined as the first occurrence since baseline of new lesions or progression of non-target lesions. Time to CNS progressive disease is defined as time from randomization to the date of progressive disease, last known follow-up (censored), or death (competing risk). Progression rates are estimated using the cumulative incidence method. One-year rates are provided.	From randomization to last follow-up. MRIs occurred at baseline, 4 and 12 weeks post RT, then every 12 weeks thereafter until progression. Maximum follow-up at time of analysis was 71.6 months.
Targeted Lesion-specific Objective Response Rate Using the RECIST 1.1 Measurement Criteria Based on Brain MRI	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Objective response is defined as a complete or partial response. Complete response is defined as the complete disappearance of all enhancing disease and partial response is defined as ≥ 30% reduction in the diameter of the target lesion. Lesions were evaluated individually. Rate is calculated by dividing the number of lesions with objective response by the number of analyzable lesions.	Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)
Targeted Lesion-specific Progression Rate Using the RECIST 1.1 Measurement Criteria Based on Brain MRI	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Progression is defined as ≥ 20% increase in the diameter of the target lesion relative to nadir. Lesions were evaluated individually. Rate is calculated by dividing the number of lesions with progression by the number of analyzable lesions.	Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)
Frequency of Highest Treatment-related Adverse Event Per Participant	Adverse events reported as definitely, probably, or possibly related to protocol treatment. Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data provided in this outcome measure. See Adverse Events Module for specific Adverse Event data.	From randomization to last follow-up. Maximum follow-up at time of analysis was 71.6 months.
Overall Complete Response Rate in the Brain Using the RECIST 1.1 Criteria Based on Brain MRI	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Overall complete response is defined as the complete disappearance of all CNS target lesions sustained for at least 4 weeks; with no new lesions, no use of corticosteroids, and patient is stable or improved clinically. All site-reported MRI data and all site-reporting of clinical progressive disease indicators were used in this analysis. Rate is calculated by dividing the number of participants with overall complete response by the number of analyzable participants.	From randomization to last follow-up. MRIs occurred at baseline, 4 and 12 weeks post RT, then every 12 weeks thereafter until progression. Maximum follow-up at time of analysis was 71.6 months.
Overall Progression Rate in the Brain Using the RECIST 1.1 Criteria Based on Brain MRI	The RECIST criteria evaluates changes in the largest diameter (unidimensional measurement) of the tumor lesions. Overall progression is defined as unequivocal progression, new or worsening tumor-related neurological symptoms, tumor-related increase in steroid dose, new primary in brain, or progression in target lesions. All site-reported MRI data and all site-reporting of clinical progressive disease indicators were used in this analysis. Rate is calculated by dividing the number of participants with progression by the number of analyzable participants.	From randomization to last follow-up. MRIs occurred at baseline, 4 and 12 weeks post RT, then every 12 weeks thereafter until progression. Maximum follow-up at time of analysis was 71.6 months.
Overall Survival (OS)	An event for overall survival is death due to any cause. Survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis occurred after 101 deaths were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 71.6 months.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: NRG Oncology
• Investigators: Principal Investigator: In A Kim, NRG Oncology

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2012
• Primary Completion (Actual): December 30, 2019
• Study Completion (Actual): May 20, 2022

Study Registration Dates

• First Submitted: June 15, 2012
• First Submitted That Met QC Criteria: June 15, 2012
• First Posted (Estimated): June 19, 2012

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Breast Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms; Breast Neoplasms; Carcinoma; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lapatinib
• Other Study ID Numbers: NCI-2012-01977 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180868 (U.S. NIH Grant/Contract); U10CA021661 (U.S. NIH Grant/Contract); RTOG-1119 (Other Identifier: CTEP); CDR0000735353