AzTrials
AzTrials

HER2-Positive Breast CarcinomaPhase 2NCT01622868

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

A Phase 2 study testing Laboratory Biomarker Analysis, Lapatinib Ditosylate and Stereotactic Radiosurgery in people with HER2-Positive Breast Carcinoma and Invasive Breast Carcinoma, run by National Cancer Institute (NCI) at 302 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Lapatinib Ditosylate and Stereotactic Radiosurgery
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
143 participants
Where
302 sitesin 3 countries
Study dates
6 Dec 2012to 20 May 2022
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

302 sites in 3 countries.

302 sites in 3 countries

United States292 sites

  • Jefferson Abington Hospital

    Abington, Pennsylvania, 19001

  • Bixby Medical Center

    Adrian, Michigan, 49221

  • Hickman Cancer Center

    Adrian, Michigan, 49221

  • Summa Health System - Akron Campus

    Akron, Ohio, 44304

  • Cleveland Clinic Akron General

    Akron, Ohio, 44307

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87102

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • Radiation Oncology Center

    Alliance, Ohio, 44601

  • AnMed Health Cancer Center

    Anderson, South Carolina, 29621

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Sutter Auburn Faith Hospital

    Auburn, California, 95602

  • Sutter Cancer Centers Radiation Oncology Services-Auburn

    Auburn, California, 95603

  • Rush - Copley Medical Center

    Aurora, Illinois, 60504

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Summa Health System - Barberton Campus

    Barberton, Ohio, 44203

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Cleveland Clinic Cancer Center Beachwood

    Beachwood, Ohio, 44122

  • UHHS-Chagrin Highlands Medical Center

    Beachwood, Ohio, 44122

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • Central Vermont Medical Center/National Life Cancer Treatment

    Berlin Corners, Vermont, 05602

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • Spectrum Health Big Rapids Hospital

    Big Rapids, Michigan, 49307

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • The Kirklin Clinic at Acton Road

    Birmingham, Alabama, 35243

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Toledo Clinic Cancer Centers-Bowling Green

    Bowling Green, Ohio, 43402

  • Saint Joseph Mercy Brighton

    Brighton, Michigan, 48114

  • New York-Presbyterian/Brooklyn Methodist Hospital

    Brooklyn, New York, 11215

  • Henry Ford Cancer Institute-Downriver

    Brownstown, Michigan, 48183

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Mills-Peninsula Medical Center

    Burlingame, California, 94010

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park

    Cameron Park, California, 95682

  • Saint Joseph Mercy Canton

    Canton, Michigan, 48188

  • Cleveland Clinic Mercy Hospital

    Canton, Ohio, 44708

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Mercy San Juan Medical Center

    Carmichael, California, 95608

  • Saint Luke's Hospital

    Cedar Rapids, Iowa, 52402

  • Dayton Physicians LLC-Miami Valley South

    Centerville, Ohio, 45459

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Geauga Hospital

    Chardon, Ohio, 44024

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Saint Joseph Mercy Chelsea

    Chelsea, Michigan, 48118

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612

  • UChicago Medicine Comprehensive Cancer Center - Saint Joseph Hospital

    Chicago, Illinois, 60657

  • Oncology Hematology Care Inc-Kenwood

    Cincinnati, Ohio, 45236

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Henry Ford Macomb Hospital-Clinton Township

    Clinton Township, Michigan, 48038

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Northside Hospital-Forsyth

    Cumming, Georgia, 30041

  • Carle on Vermilion

    Danville, Illinois, 61832

  • Sutter Davis Hospital

    Davis, California, 95616

  • Good Samaritan Hospital - Dayton

    Dayton, Ohio, 45406

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Dayton Physician LLC-Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Beaumont Hospital - Dearborn

    Dearborn, Michigan, 48124

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Ascension Saint John Hospital

    Detroit, Michigan, 48236

  • Epic Care-Dublin

    Dublin, California, 94568

  • Pocono Medical Center

    East Stroudsburg, Pennsylvania, 18301

  • Hematology Oncology Associates of Central New York-East Syracuse

    East Syracuse, New York, 13057

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Elkhart Clinic

    Elkhart, Indiana, 46514-2098

  • Michiana Hematology Oncology PC-Elkhart

    Elkhart, Indiana, 46514

  • Elkhart General Hospital

    Elkhart, Indiana, 46515

  • Mercy Cancer Center-Elyria

    Elyria, Ohio, 44035

  • Bay Area Breast Surgeons Inc

    Emeryville, California, 94608

  • Epic Care Partners in Cancer Care

    Emeryville, California, 94608

  • Green Bay Oncology - Escanaba

    Escanaba, Michigan, 49829

  • Piedmont Fayette Hospital

    Fayetteville, Georgia, 30214

  • Armes Family Cancer Center

    Findlay, Ohio, 45840

  • Blanchard Valley Hospital

    Findlay, Ohio, 45840

  • Orion Cancer Care

    Findlay, Ohio, 45840

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Radiation Oncology Associates PC

    Fort Wayne, Indiana, 46804

  • Parkview Hospital Randallia

    Fort Wayne, Indiana, 46805

  • Parkview Regional Medical Center

    Fort Wayne, Indiana, 46845

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Dayton Physicians LLC-Atrium

    Franklin, Ohio, 45005

  • Fredericksburg Oncology Inc

    Fredericksburg, Virginia, 22401

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Gibbs Cancer Center-Gaffney

    Gaffney, South Carolina, 29341

  • Northeast Georgia Medical Center-Gainesville

    Gainesville, Georgia, 30501

  • Central Care Cancer Center - Garden City

    Garden City, Kansas, 67846

  • Mercy Health Saint Mary's

    Grand Rapids, Michigan, 49503

  • Spectrum Health at Butterworth Campus

    Grand Rapids, Michigan, 49503

  • Central Care Cancer Center - Great Bend

    Great Bend, Kansas, 67530

  • Green Bay Oncology at Saint Vincent Hospital

    Green Bay, Wisconsin, 54301-3526

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Green Bay Oncology Limited at Saint Mary's Hospital

    Green Bay, Wisconsin, 54303

  • Saint Vincent Hospital Cancer Center at Saint Mary's

    Green Bay, Wisconsin, 54303

  • Dayton Physicians LLC-Wayne

    Greenville, Ohio, 45331

  • Wayne Hospital

    Greenville, Ohio, 45331

  • Gibbs Cancer Center-Pelham

    Greer, South Carolina, 29651

  • Legacy Mount Hood Medical Center

    Gresham, Oregon, 97030

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • AdventHealth Hendersonville

    Hendersonville, North Carolina, 28792

  • Centerpoint Medical Center LLC

    Independence, Missouri, 64057

  • Cleveland Clinic Cancer Center Independence

    Independence, Ohio, 44131

  • Green Bay Oncology - Iron Mountain

    Iron Mountain, Michigan, 49801

  • Allegiance Health

    Jackson, Michigan, 49201

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • UW Cancer Center Johnson Creek

    Johnson Creek, Wisconsin, 53038

  • Mercy Hospital Joplin

    Joplin, Missouri, 64804

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Borgess Medical Center

    Kalamazoo, Michigan, 49048

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • North Kansas City Hospital

    Kansas City, Missouri, 64116

  • Heartland Hematology and Oncology Associates Incorporated

    Kansas City, Missouri, 64118

  • Research Medical Center

    Kansas City, Missouri, 64132

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Community Howard Regional Health

    Kokomo, Indiana, 46904

  • IU Health La Porte Hospital

    La Porte, Indiana, 46350

  • Sparrow Hospital

    Lansing, Michigan, 48912

  • Memorial Medical Center - Las Cruces

    Las Cruces, New Mexico, 88011

  • Saint Luke's East - Lee's Summit

    Lee's Summit, Missouri, 64086

  • Kansas Institute of Medicine Cancer and Blood Center

    Lenexa, Kansas, 66219

  • Minimally Invasive Surgery Hospital

    Lenexa, Kansas, 66219

  • Beebe Medical Center

    Lewes, Delaware, 19958

  • Liberty Radiation Oncology Center

    Liberty, Missouri, 64068

  • Lima Memorial Hospital

    Lima, Ohio, 45804

  • Saint Barnabas Medical Center

    Livingston, New Jersey, 07039

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • Norton Hospital Pavilion and Medical Campus

    Louisville, Kentucky, 40202

  • Norton Suburban Hospital and Medical Campus

    Louisville, Kentucky, 40207

  • Covenant Medical Center-Lakeside

    Lubbock, Texas, 79410

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Elliot Hospital

    Manchester, New Hampshire, 03103

  • Holy Family Memorial Hospital

    Manitowoc, Wisconsin, 54221

  • Cleveland Clinic Cancer Center Mansfield

    Mansfield, Ohio, 44906

  • Fairview Clinics and Surgery Center Maple Grove

    Maple Grove, Minnesota, 55369

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • Saint John's Hospital - Healtheast

    Maplewood, Minnesota, 55109

  • Bay Area Medical Center

    Marinette, Wisconsin, 54143

  • Contra Costa Regional Medical Center

    Martinez, California, 94553-3156

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Toledo Clinic Cancer Centers-Maumee

    Maumee, Ohio, 43537

  • Toledo Radiation Oncology at Northwest Ohio Onocolgy Center

    Maumee, Ohio, 43537

  • Hillcrest Hospital Cancer Center

    Mayfield Heights, Ohio, 44124

  • Summa Health Medina Medical Center

    Medina, Ohio, 44256

  • UH Seidman Cancer Center at Lake Health Mentor Campus

    Mentor, Ohio, 44060

  • Ascension Columbia Saint Mary's Hospital Ozaukee

    Mequon, Wisconsin, 53097

  • Idaho Urologic Institute-Meridian

    Meridian, Idaho, 83642

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Miami Cancer Institute

    Miami, Florida, 33176

  • UH Seidman Cancer Center at Southwest General Hospital

    Middleburg Heights, Ohio, 44130

  • Ascension Columbia Saint Mary's Hospital - Milwaukee

    Milwaukee, Wisconsin, 53211

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • Health Partners Inc

    Minneapolis, Minnesota, 55454

  • Memorial Regional Cancer Center Day Road

    Mishawaka, Indiana, 46545

  • Michiana Hematology Oncology PC-Mishawaka

    Mishawaka, Indiana, 46545

  • Saint Joseph Regional Medical Center-Mishawaka

    Mishawaka, Indiana, 46545

  • University of South Alabama Mitchell Cancer Institute

    Mobile, Alabama, 36688

  • Memorial Medical Center

    Modesto, California, 95355

  • Mercy Memorial Hospital

    Monroe, Michigan, 48162

  • Toledo Clinic Cancer Centers-Monroe

    Monroe, Michigan, 48162

  • Virtua Memorial

    Mount Holly, New Jersey, 08060

  • Good Samaritan Regional Health Center

    Mount Vernon, Illinois, 62864

  • Palo Alto Medical Foundation-Camino Division

    Mountain View, California, 94040

  • Palo Alto Medical Foundation-Gynecologic Oncology

    Mountain View, California, 94040

  • Mercy Health Mercy Campus

    Muskegon, Michigan, 49444

  • The Hospital of Central Connecticut

    New Britain, Connecticut, 06050

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • Cancer Center of Western Wisconsin

    New Richmond, Wisconsin, 54017

  • Mount Sinai Hospital

    New York, New York, 10029

  • Christiana Gynecologic Oncology LLC

    Newark, Delaware, 19713

  • Delaware Clinical and Laboratory Physicians PA

    Newark, Delaware, 19713

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, 19713

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Lakeland Hospital Niles

    Niles, Michigan, 49120

  • Sutter Cancer Research Consortium

    Novato, California, 94945

  • Alta Bates Summit Medical Center - Summit Campus

    Oakland, California, 94609

  • Bay Area Tumor Institute

    Oakland, California, 94609

  • Saint Vincent Hospital Cancer Center at Oconto Falls

    Oconto Falls, Wisconsin, 54154

  • Saint Charles Hospital

    Oregon, Ohio, 43616

  • Toledo Clinic Cancer Centers-Oregon

    Oregon, Ohio, 43616

  • Menorah Medical Center

    Overland Park, Kansas, 66209

  • Saint Luke's South Hospital

    Overland Park, Kansas, 66213

  • Palo Alto Medical Foundation Health Care

    Palo Alto, California, 94301

  • Stanford Cancer Institute Palo Alto

    Palo Alto, California, 94304

  • University Hospitals Parma Medical Center

    Parma, Ohio, 44129

  • Singing River Hospital

    Pascagoula, Mississippi, 39581

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Saint Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

  • Michiana Hematology Oncology PC-Plymouth

    Plymouth, Indiana, 46563

  • 21st Century Oncology-Pontiac

    Pontiac, Michigan, 48341

  • Saint Joseph Mercy Oakland

    Pontiac, Michigan, 48341

  • Lake Huron Medical Center

    Port Huron, Michigan, 48060

  • Legacy Good Samaritan Hospital and Medical Center

    Portland, Oregon, 97210

  • University Hospitals Portage Medical Center

    Ravenna, Ohio, 44266

  • Beebe Health Campus

    Rehoboth Beach, Delaware, 19971

  • Renown Regional Medical Center

    Reno, Nevada, 89502

  • Reid Health

    Richmond, Indiana, 47374

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

  • North Memorial Medical Health Center

    Robbinsdale, Minnesota, 55422

  • Highland Hospital

    Rochester, New York, 14620

  • University of Rochester

    Rochester, New York, 14642

  • Delbert Day Cancer Institute at PCRMC

    Rolla, Missouri, 65401

  • Mercy Clinic-Rolla-Cancer and Hematology

    Rolla, Missouri, 65401

  • Sutter Cancer Centers Radiation Oncology Services-Roseville

    Roseville, California, 95661

  • Sutter Roseville Medical Center

    Roseville, California, 95661

  • Sutter Medical Center Sacramento

    Sacramento, California, 95816

  • Mercy General Hospital Radiation Oncology Center

    Sacramento, California, 95819

  • Ascension Saint Mary's Hospital

    Saginaw, Michigan, 48601

  • Lakeland Medical Center Saint Joseph

    Saint Joseph, Michigan, 49085

  • Marie Yeager Cancer Center

    Saint Joseph, Michigan, 49085

  • Heartland Regional Medical Center

    Saint Joseph, Missouri, 64506

  • Saint Joseph Oncology Inc

    Saint Joseph, Missouri, 64507

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • UH Seidman Cancer Center at Salem Regional Medical Center

    Salem, Ohio, 44460

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • California Pacific Medical Center-Pacific Campus

    San Francisco, California, 94115

  • North Coast Cancer Care

    Sandusky, Ohio, 44870

  • Palo Alto Medical Foundation-Santa Cruz

    Santa Cruz, California, 95065

  • Sutter Pacific Medical Foundation

    Santa Rosa, California, 95403

  • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler

    Savannah, Georgia, 31405

  • TidalHealth Nanticoke / Allen Cancer Center

    Seaford, Delaware, 19973

  • Memorial Hospital of South Bend

    South Bend, Indiana, 46601

  • Michiana Hematology Oncology PC-South Bend

    South Bend, Indiana, 46601

  • South Bend Clinic

    South Bend, Indiana, 46617

  • Spartanburg Medical Center

    Spartanburg, South Carolina, 29303

  • Mercy Hospital Springfield

    Springfield, Missouri, 65804

  • CoxHealth South Hospital

    Springfield, Missouri, 65807

  • Springfield Regional Cancer Center

    Springfield, Ohio, 45504

  • Springfield Regional Medical Center

    Springfield, Ohio, 45505

  • Saint Louis Cancer and Breast Institute-South City

    St Louis, Missouri, 63109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Saint Louis-Cape Girardeau CCOP

    St Louis, Missouri, 63141

  • Iredell Memorial Hospital

    Statesville, North Carolina, 28677

  • Cleveland Clinic Cancer Center Strongsville

    Strongsville, Ohio, 44136

  • Saint Vincent Hospital Cancer Center at Sturgeon Bay

    Sturgeon Bay, Wisconsin, 54235-1495

  • Green Bay Oncology - Sturgeon Bay

    Sturgeon Bay, Wisconsin, 54235

  • Palo Alto Medical Foundation-Sunnyvale

    Sunnyvale, California, 94086

  • ProMedica Flower Hospital

    Sylvania, Ohio, 43560

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • Mercy Hospital of Tiffin

    Tiffin, Ohio, 44883

  • Saint Vincent Mercy Medical Center

    Toledo, Ohio, 43608

  • University of Toledo

    Toledo, Ohio, 43614

  • Toledo Community Hospital Oncology Program CCOP

    Toledo, Ohio, 43617

  • Mercy Health - Saint Anne Hospital

    Toledo, Ohio, 43623

  • Toledo Clinic Cancer Centers-Toledo

    Toledo, Ohio, 43623

  • Munson Medical Center

    Traverse City, Michigan, 49684

  • Dayton Physicians LLC-Upper Valley

    Troy, Ohio, 45373

  • Upper Valley Medical Center

    Troy, Ohio, 45373

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

  • Natalie Warren Bryant Cancer Center at Saint Francis

    Tulsa, Oklahoma, 74136

  • Warren Clinic Oncology-Tulsa

    Tulsa, Oklahoma, 74146

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • Sutter Cancer Centers Radiation Oncology Services-Vacaville

    Vacaville, California, 95687

  • Sutter Solano Medical Center/Cancer Center

    Vallejo, California, 94589

  • Legacy Salmon Creek Hospital

    Vancouver, Washington, 98686

  • Virtua Voorhees

    Voorhees Township, New Jersey, 08043

  • Ridgeview Medical Center

    Waconia, Minnesota, 55387

  • Epic Care Cyberknife Center

    Walnut Creek, California, 94597

  • Saint John Macomb-Oakland Hospital

    Warren, Michigan, 48093

  • Fulton County Health Center

    Wauseon, Ohio, 43567

  • Henry Ford West Bloomfield Hospital

    West Bloomfield, Michigan, 48322

  • Reading Hospital

    West Reading, Pennsylvania, 19611

  • UHHS-Westlake Medical Center

    Westlake, Ohio, 44145

  • Michiana Hematology Oncology PC-Westville

    Westville, Indiana, 46391

  • Wheeling Hospital/Schiffler Cancer Center

    Wheeling, West Virginia, 26003

  • Rice Memorial Hospital

    Willmar, Minnesota, 56201

  • Christiana Care Health System-Wilmington Hospital

    Wilmington, Delaware, 19801

  • Cancer Treatment Center

    Wooster, Ohio, 44691

  • Cleveland Clinic Wooster Family Health and Surgery Center

    Wooster, Ohio, 44691

  • Metro Health Hospital

    Wyoming, Michigan, 49519

Other trials in United States

South Korea8 sites

  • Keimyung University-Dongsan Medical Center

    Dalseo-gu, Daegu, 42601

  • National Cancer Center-Korea

    Goyang-si, Gyeonggi-do, 410-769

  • Chonnam National University Hwasun Hospital

    Hwasun-gun, Jeollanam-do, 519-763

  • Seoul National University Bundang Hospital

    Seongnam, Kyeonggi-do, 463-707

  • Samsung Medical Center

    Seoul, Korea, 135-710

  • Gangnam Severance Hospital

    Seoul, 06273

  • Seoul National University Hospital

    Seoul, 110-744

  • Yonsei University Health System-Severance Hospital

    Seoul, 120-752

Other trials in South Korea

Canada2 sites

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

Other trials in Canada

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

Being tested
Laboratory Biomarker Analysis, Lapatinib Ditosylate, Stereotactic Radiosurgery, Whole-Brain Radiotherapy
Medical subject headings
Brain Neoplasms, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Lapatinib DitosylateDrug

    Also called Tykerb

    Given PO

  • Stereotactic RadiosurgeryRadiation

    Also called Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy, Stereotactic Radiotherapy

    Undergo SRS

  • Whole-Brain RadiotherapyRadiation

    Also called WBRT, whole-brain radiation therapy

    Undergo WBRT

Study groups in NCT01622868
Study groupRoleWhat they receive
Arm A (WBRT or SRS)ExperimentalPatients undergo WBRT 5 days a week for 3 weeks for a total of 15 treatments, or SRS for 1 treatment.
Receives: Other: Laboratory Biomarker Analysis; Radiation: Stereotactic Radiosurgery; Radiation: Whole-Brain Radiotherapy
Arm B (lapatinib ditosylate, WBRT or SRS)ExperimentalPatients undergo WBRT or SRS as in Arm A. Patients also receive lapatinib ditosylate PO QD for 6 weeks.
Receives: Other: Laboratory Biomarker Analysis; Drug: Lapatinib Ditosylate; Radiation: Stereotactic Radiosurgery; Radiation: Whole-Brain Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline and 12 weeks post RT (approximately 12 weeks from start of treatment if SRS and 15 if WBRT)

Secondary outcomes (10)

  1. 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.

    Measured: Baseline and 4 weeks post RT (approximately 4 weeks from start of treatment if SRS and 7 if WBRT)

  2. 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.

    Measured: Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)

  3. 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.

    Measured: Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)

  4. 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.

    Measured: 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.

  5. 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.

    Measured: Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)

  6. 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.

    Measured: Baseline, 4 and 12 weeks post RT (approximately 4 and 12 weeks from start of treatment if SRS, 7 and 15 if WBRT)

  7. 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.

    Measured: From randomization to last follow-up. Maximum follow-up at time of analysis was 71.6 months.

  8. 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.

    Measured: 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.

  9. 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.

    Measured: 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.

  10. 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.

    Measured: From randomization to last follow-up. Maximum follow-up at time of analysis was 71.6 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jun 2012 (estimated)
  2. Study start6 Dec 2012
  3. Primary completion30 Dec 2019
  4. Study completion20 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
143 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01622868
Sponsor's protocol ID
NCI-2012-01977
Other IDs
NCI-2012-01977, RTOG-1119, CDR0000735353, RTOG-1119, RTOG-1119, U10CA180868, U10CA021661
Status last verified
Sep 2023
First submitted
15 Jun 2012
Last updated
17 Oct 2023
Data monitoring committee
No

Publications

  • Kim IA, Winter KA, Sperduto PW, De Los Santos JF, Peereboom DM, Ogunleye T, Boulter D, Fritz JM, Cho KH, Shin KH, Zoberi I, Choi S, Palmer JD, Liem B, Kim YB, Anderson BM, Thakrar AW, Muanza TM, Kim MM, Choi DH, Mehta MP, White JR. Concurrent Lapatinib With Brain Radiation Therapy in Patients With HER2+ Breast Cancer With Brain Metastases: NRG Oncology-KROG/RTOG 1119 Phase 2 Randomized Trial. Int J Radiat Oncol Biol Phys. 2024 Apr 1;118(5):1391-1401. doi: 10.1016/j.ijrobp.2023.07.019. Epub 2023 Jul 26.

    PubMed 37506981

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