Whole-Brain Radiation Therapy or Stereotactic Radiosurgery With or Without Lapatinib Ditosylate in Treating Patients With Brain Metastasis From HER2-Positive Breast Cancer
HER2-Positive Breast Carcinoma, Invasive Breast Carcinoma, Metastatic Malignant Neoplasm in the Brain
About this trial
This is an interventional treatment trial for HER2-Positive Breast Carcinoma
Eligibility Criteria
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
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- The Kirklin Clinic at Acton Road
- University of South Alabama Mitchell Cancer Institute
- Saint Joseph's Hospital and Medical Center
- Banner University Medical Center - Tucson
- Sutter Auburn Faith Hospital
- Sutter Cancer Centers Radiation Oncology Services-Auburn
- Alta Bates Summit Medical Center-Herrick Campus
- Mills-Peninsula Medical Center
- Sutter Cancer Centers Radiation Oncology Services-Cameron Park
- Mercy San Juan Medical Center
- Sutter Davis Hospital
- Epic Care-Dublin
- Bay Area Breast Surgeons Inc
- Epic Care Partners in Cancer Care
- Contra Costa Regional Medical Center
- Memorial Medical Center
- Palo Alto Medical Foundation-Camino Division
- Palo Alto Medical Foundation-Gynecologic Oncology
- Sutter Cancer Research Consortium
- Alta Bates Summit Medical Center - Summit Campus
- Bay Area Tumor Institute
- Palo Alto Medical Foundation Health Care
- Stanford Cancer Institute Palo Alto
- Sutter Cancer Centers Radiation Oncology Services-Roseville
- Sutter Roseville Medical Center
- Sutter Medical Center Sacramento
- Mercy General Hospital Radiation Oncology Center
- California Pacific Medical Center-Pacific Campus
- Palo Alto Medical Foundation-Santa Cruz
- Sutter Pacific Medical Foundation
- Palo Alto Medical Foundation-Sunnyvale
- Sutter Cancer Centers Radiation Oncology Services-Vacaville
- Sutter Solano Medical Center/Cancer Center
- Epic Care Cyberknife Center
- Smilow Cancer Hospital Care Center at Saint Francis
- The Hospital of Central Connecticut
- Beebe Medical Center
- Christiana Gynecologic Oncology LLC
- Delaware Clinical and Laboratory Physicians PA
- Helen F Graham Cancer Center
- Medical Oncology Hematology Consultants PA
- Christiana Care Health System-Christiana Hospital
- Beebe Health Campus
- TidalHealth Nanticoke / Allen Cancer Center
- Christiana Care Health System-Wilmington Hospital
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Miami Cancer Institute
- Piedmont Hospital
- Northside Hospital
- Northside Hospital-Forsyth
- Piedmont Fayette Hospital
- Northeast Georgia Medical Center-Gainesville
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Saint Alphonsus Cancer Care Center-Boise
- Saint Alphonsus Cancer Care Center-Caldwell
- Idaho Urologic Institute-Meridian
- Rush - Copley Medical Center
- John H Stroger Jr Hospital of Cook County
- UChicago Medicine Comprehensive Cancer Center - Saint Joseph Hospital
- Carle on Vermilion
- Carle Physician Group-Effingham
- Carle Physician Group-Mattoon/Charleston
- Good Samaritan Regional Health Center
- Carle Cancer Center
- Elkhart Clinic
- Michiana Hematology Oncology PC-Elkhart
- Elkhart General Hospital
- Radiation Oncology Associates PC
- Parkview Hospital Randallia
- Parkview Regional Medical Center
- Community Howard Regional Health
- IU Health La Porte Hospital
- Memorial Regional Cancer Center Day Road
- Michiana Hematology Oncology PC-Mishawaka
- Saint Joseph Regional Medical Center-Mishawaka
- Michiana Hematology Oncology PC-Plymouth
- Reid Health
- Memorial Hospital of South Bend
- Michiana Hematology Oncology PC-South Bend
- South Bend Clinic
- Michiana Hematology Oncology PC-Westville
- Saint Luke's Hospital
- Central Care Cancer Center - Garden City
- Central Care Cancer Center - Great Bend
- Kansas Institute of Medicine Cancer and Blood Center
- Minimally Invasive Surgery Hospital
- Menorah Medical Center
- Saint Luke's South Hospital
- Norton Hospital Pavilion and Medical Campus
- Norton Suburban Hospital and Medical Campus
- Ochsner Medical Center Jefferson
- Greater Baltimore Medical Center
- Boston Medical Center
- Bixby Medical Center
- Hickman Cancer Center
- Saint Joseph Mercy Hospital
- University of Michigan Comprehensive Cancer Center
- Bronson Battle Creek
- Spectrum Health Big Rapids Hospital
- Saint Joseph Mercy Brighton
- Henry Ford Cancer Institute-Downriver
- Saint Joseph Mercy Canton
- Saint Joseph Mercy Chelsea
- Henry Ford Macomb Hospital-Clinton Township
- Beaumont Hospital - Dearborn
- Henry Ford Hospital
- Ascension Saint John Hospital
- Green Bay Oncology - Escanaba
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Mercy Health Saint Mary's
- Spectrum Health at Butterworth Campus
- Green Bay Oncology - Iron Mountain
- Allegiance Health
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Borgess Medical Center
- Sparrow Hospital
- Trinity Health Saint Mary Mercy Livonia Hospital
- Mercy Memorial Hospital
- Toledo Clinic Cancer Centers-Monroe
- Mercy Health Mercy Campus
- Lakeland Hospital Niles
- 21st Century Oncology-Pontiac
- Saint Joseph Mercy Oakland
- Lake Huron Medical Center
- Ascension Saint Mary's Hospital
- Lakeland Medical Center Saint Joseph
- Marie Yeager Cancer Center
- Munson Medical Center
- Saint John Macomb-Oakland Hospital
- Henry Ford West Bloomfield Hospital
- Metro Health Hospital
- Fairview Ridges Hospital
- Mercy Hospital
- Fairview Southdale Hospital
- Unity Hospital
- Fairview Clinics and Surgery Center Maple Grove
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Hennepin County Medical Center
- Health Partners Inc
- North Memorial Medical Health Center
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Ridgeview Medical Center
- Rice Memorial Hospital
- University of Mississippi Medical Center
- Singing River Hospital
- Central Care Cancer Center - Bolivar
- Saint Francis Medical Center
- Siteman Cancer Center at West County Hospital
- Centerpoint Medical Center LLC
- Mercy Hospital Joplin
- Saint Luke's Hospital of Kansas City
- North Kansas City Hospital
- Heartland Hematology and Oncology Associates Incorporated
- Research Medical Center
- Saint Luke's East - Lee's Summit
- Liberty Radiation Oncology Center
- Delbert Day Cancer Institute at PCRMC
- Mercy Clinic-Rolla-Cancer and Hematology
- Heartland Regional Medical Center
- Saint Joseph Oncology Inc
- Saint Louis Cancer and Breast Institute-South City
- Washington University School of Medicine
- Siteman Cancer Center-South County
- Mercy Hospital Saint Louis
- Saint Louis-Cape Girardeau CCOP
- Siteman Cancer Center at Saint Peters Hospital
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Renown Regional Medical Center
- Elliot Hospital
- Saint Barnabas Medical Center
- Virtua Memorial
- Virtua Voorhees
- University of New Mexico Cancer Center
- Memorial Medical Center - Las Cruces
- Montefiore Medical Center - Moses Campus
- New York-Presbyterian/Brooklyn Methodist Hospital
- Roswell Park Cancer Institute
- Hematology Oncology Associates of Central New York-East Syracuse
- Mount Sinai Hospital
- Highland Hospital
- University of Rochester
- UNC Lineberger Comprehensive Cancer Center
- AdventHealth Hendersonville
- Iredell Memorial Hospital
- Summa Health System - Akron Campus
- Cleveland Clinic Akron General
- Radiation Oncology Center
- Summa Health System - Barberton Campus
- Cleveland Clinic Cancer Center Beachwood
- UHHS-Chagrin Highlands Medical Center
- Toledo Clinic Cancer Centers-Bowling Green
- Cleveland Clinic Mercy Hospital
- Dayton Physicians LLC-Miami Valley South
- Miami Valley Hospital South
- Geauga Hospital
- Oncology Hematology Care Inc-Kenwood
- Case Western Reserve University
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Dayton Physician LLC-Miami Valley Hospital North
- Miami Valley Hospital North
- Mercy Cancer Center-Elyria
- Armes Family Cancer Center
- Blanchard Valley Hospital
- Orion Cancer Care
- Atrium Medical Center-Middletown Regional Hospital
- Dayton Physicians LLC-Atrium
- Dayton Physicians LLC-Wayne
- Wayne Hospital
- Cleveland Clinic Cancer Center Independence
- Kettering Medical Center
- Lima Memorial Hospital
- Cleveland Clinic Cancer Center Mansfield
- Toledo Clinic Cancer Centers-Maumee
- Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
- Hillcrest Hospital Cancer Center
- Summa Health Medina Medical Center
- UH Seidman Cancer Center at Lake Health Mentor Campus
- UH Seidman Cancer Center at Southwest General Hospital
- Saint Charles Hospital
- Toledo Clinic Cancer Centers-Oregon
- University Hospitals Parma Medical Center
- University Hospitals Portage Medical Center
- UH Seidman Cancer Center at Salem Regional Medical Center
- North Coast Cancer Care
- Springfield Regional Cancer Center
- Springfield Regional Medical Center
- Cleveland Clinic Cancer Center Strongsville
- ProMedica Flower Hospital
- Mercy Hospital of Tiffin
- Saint Vincent Mercy Medical Center
- University of Toledo
- Toledo Community Hospital Oncology Program CCOP
- Mercy Health - Saint Anne Hospital
- Toledo Clinic Cancer Centers-Toledo
- Dayton Physicians LLC-Upper Valley
- Upper Valley Medical Center
- Fulton County Health Center
- UHHS-Westlake Medical Center
- Cancer Treatment Center
- Cleveland Clinic Wooster Family Health and Surgery Center
- Natalie Warren Bryant Cancer Center at Saint Francis
- Warren Clinic Oncology-Tulsa
- Legacy Mount Hood Medical Center
- Legacy Good Samaritan Hospital and Medical Center
- Jefferson Abington Hospital
- Lehigh Valley Hospital-Cedar Crest
- Lehigh Valley Hospital - Muhlenberg
- Pocono Medical Center
- Thomas Jefferson University Hospital
- Reading Hospital
- AnMed Health Cancer Center
- Medical University of South Carolina
- Gibbs Cancer Center-Gaffney
- Gibbs Cancer Center-Pelham
- Spartanburg Medical Center
- Covenant Medical Center-Lakeside
- University of Texas Health Science Center at San Antonio
- Central Vermont Medical Center/National Life Cancer Treatment
- University of Vermont Medical Center
- University of Vermont and State Agricultural College
- Fredericksburg Oncology Inc
- Virginia Commonwealth University/Massey Cancer Center
- Legacy Salmon Creek Hospital
- Wheeling Hospital/Schiffler Cancer Center
- Green Bay Oncology at Saint Vincent Hospital
- Saint Vincent Hospital Cancer Center Green Bay
- Green Bay Oncology Limited at Saint Mary's Hospital
- Saint Vincent Hospital Cancer Center at Saint Mary's
- UW Cancer Center Johnson Creek
- University of Wisconsin Carbone Cancer Center
- Holy Family Memorial Hospital
- Bay Area Medical Center
- Ascension Columbia Saint Mary's Hospital Ozaukee
- Ascension Columbia Saint Mary's Hospital - Milwaukee
- Medical College of Wisconsin
- Cancer Center of Western Wisconsin
- Saint Vincent Hospital Cancer Center at Oconto Falls
- Saint Vincent Hospital Cancer Center at Sturgeon Bay
- Green Bay Oncology - Sturgeon Bay
- Juravinski Cancer Centre at Hamilton Health Sciences
- Jewish General Hospital
- Keimyung University-Dongsan Medical Center
- National Cancer Center-Korea
- Chonnam National University Hwasun Hospital
- Samsung Medical Center
- Seoul National University Bundang Hospital
- Gangnam Severance Hospital
- Seoul National University Hospital
- Yonsei University Health System-Severance Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm A (WBRT or SRS)
Arm B (lapatinib ditosylate, WBRT or SRS)
Patients undergo WBRT 5 days a week for 3 weeks for a total of 15 treatments, or SRS for 1 treatment.
Patients undergo WBRT or SRS as in Arm A. Patients also receive lapatinib ditosylate PO QD for 6 weeks.