A Randomized Phase III Trial of Memantine and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Patients With Brain Metastases

Status: Completed
Location: See all (220) locations...
Intervention Type: Radiation, Drug
Study Type: Interventional
Study Phase: Phase 3
SUMMARY

This randomized phase III trial compares memantine hydrochloride and whole-brain radiotherapy with or without hippocampal avoidance in reducing neurocognitive decline in patients with cancer that has spread from the primary site (place where it started) to the brain. Whole brain radiotherapy (WBRT) is the most common treatment for brain metastasis. Unfortunately, the majority of patients with brain metastases experience cognitive (such as learning and memory) deterioration after WBRT. Memantine hydrochloride may enhance cognitive function by binding to and inhibiting channels of receptors located in the central nervous system. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Using radiation techniques, such as intensity modulated radiotherapy to avoid the hippocampal region during WBRT, may reduce the radiation dose to the hippocampus and help limit the radiation-induced cognitive decline. It is not yet known whether giving memantine hydrochloride and WBRT with or without hippocampal avoidance works better in reducing neurocognitive decline in patients with brain metastases.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No
View:

• PRIOR TO STEP 1 REGISTRATION:

• Brain metastases outside a 5-mm margin around either hippocampus must be visible on contrast-enhanced magnetic resonance imaging (MRI) performed =< 21 days prior to Step 1 registration; an allowed exception, regarding ability to image brain metastases, would be that patients who had undergone radiosurgery or surgical resection and are planning adjuvant WBRT do not have to have visible disease but do need a pre-surgery MRI or computed tomography (CT) scan demonstrating brain metastases; however, the brain metastases could not have been within 5 mm of either hippocampus

• Patients must have a gadolinium contrast-enhanced three-dimensional spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) axial MRI scan with standard axial and coronal gadolinium contrast-enhanced T1-weighted sequence and axial T2/FLAIR sequence acquisitions; to yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE, or TFE axial MRI scan should use the smallest possible axial slice thickness not exceeding 1.5 mm; the associated coronal and sagittal contrast-enhanced T1 sequences can be up to 2.5 mm in slice thickness; this MRI must be obtained =< 21 days prior to step 1 registration; the vendor specific MRI protocols are available for download from the Alzheimer's Disease Neuroimaging Initiative (ADNI)

• Patients must provide study-specific informed consent prior to registration

• PRIOR TO STEP 2 REGISTRATION:

• The following baseline neurocognitive assessments must be completed prior to Step 2 registration: HVLT-R, TMT, and COWA;

• Pathologically (histologically or cytologically) proven diagnosis of solid tumor malignancy within 5 years prior to Step 2 registration

• History and physical examination within 28 days prior to Step 2 registration

• Karnofsky performance status of >= 70 within 28 days prior to Step 2 registration

• Serum creatinine =< 3 mg/dL (265 umol/L) and creatinine clearance >= 30 ml/min

• Blood urea nitrogen (BUN) within institutional upper limit of normal (e.g. < 20 mg/dL)

• Total bilirubin =< 2.5 mg/dL (43 umol/L)

• Patients may have had prior therapy for brain metastasis, including radiosurgery and surgical resection; patients must have completed prior therapy by at least 14 days prior to Step 2 for surgical resection and 7 days for radiosurgery

• Negative serum pregnancy test (in women of childbearing potential) =< 14 days prior to Step 2; women of childbearing potential and men who are sexually active must practice adequate contraception while on study

• Patients who are primary English or French speakers are eligible

Locations
United States
Alabama
Lewis and Faye Manderson Cancer Center
Tuscaloosa
Arizona
Banner MD Anderson Cancer Center
Gilbert
Banner University Medical Center - Tucson
Tucson
California
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank
Mercy San Juan Medical Center
Carmichael
City of Hope Comprehensive Cancer Center
Duarte
UC San Diego Moores Cancer Center
La Jolla
Kaiser Permanente Los Angeles Medical Center
Los Angeles
Los Angeles County-USC Medical Center
Los Angeles
USC / Norris Comprehensive Cancer Center
Los Angeles
Kaiser Permanente Oakland-Broadway
Oakland
Stanford Cancer Institute Palo Alto
Palo Alto
Kaiser Permanente-Rancho Cordova Cancer Center
Rancho Cordova
Rohnert Park Cancer Center
Rohnert Park
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville
The Permanente Medical Group-Roseville Radiation Oncology
Roseville
Mercy Cancer Center - Sacramento
Sacramento
Sutter Medical Center Sacramento
Sacramento
University of California San Diego
San Diego
California Pacific Medical Center-Pacific Campus
San Francisco
Stanford Cancer Center South Bay
San Jose
Kaiser Permanente Medical Center - Santa Clara
Santa Clara
Kaiser Permanente Cancer Treatment Center
South San Francisco
Sutter Solano Medical Center/Cancer Center
Vallejo
Colorado
Rocky Mountain Cancer Centers-Boulder
Boulder
Penrose-Saint Francis Healthcare
Colorado Springs
UCHealth Memorial Hospital Central
Colorado Springs
Swedish Medical Center
Englewood
Connecticut
Saint Vincent's Medical Center
Bridgeport
Delaware
Christiana Care Health System-Christiana Hospital
Newark
Helen F Graham Cancer Center
Newark
Florida
Boca Raton Regional Hospital
Boca Raton
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami
UF Cancer Center at Orlando Health
Orlando
Cleveland Clinic-Weston
Weston
Georgia
Emory Saint Joseph's Hospital
Atlanta
Emory University Hospital Midtown
Atlanta
Emory University Hospital/Winship Cancer Institute
Atlanta
Grady Health System
Atlanta
Piedmont Hospital
Atlanta
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Savannah
Memorial Health University Medical Center
Savannah
Iowa
Saint Luke's Hospital
Cedar Rapids
Idaho
Saint Alphonsus Cancer Care Center-Boise
Boise
Saint Luke's Mountain States Tumor Institute
Boise
Saint Luke's Mountain States Tumor Institute - Meridian
Meridian
Saint Luke's Mountain States Tumor Institute - Nampa
Nampa
Saint Luke's Mountain States Tumor Institute-Twin Falls
Twin Falls
Illinois
SIH Cancer Institute
Carterville
John H Stroger Jr Hospital of Cook County
Chicago
Northwestern University
Chicago
University of Chicago Comprehensive Cancer Center
Chicago
Decatur Memorial Hospital
Decatur
Crossroads Cancer Center
Effingham
Northwestern Medicine Cancer Center Delnor
Geneva
Edward Hines Jr VA Hospital
Hines
Condell Memorial Hospital
Libertyville
Loyola University Medical Center
Maywood
Methodist Medical Center of Illinois
Peoria
OSF Saint Francis Medical Center
Peoria
Memorial Medical Center
Springfield
Carle Cancer Center
Urbana
Northwestern Medicine Cancer Center Warrenville
Warrenville
Indiana
Parkview Hospital Randallia
Fort Wayne
Community Cancer Center East
Indianapolis
Community Cancer Center North
Indianapolis
Community Cancer Center South
Indianapolis
Kansas
University of Kansas Cancer Center
Kansas City
Lawrence Memorial Hospital
Lawrence
University of Kansas Cancer Center-Overland Park
Overland Park
Ascension Via Christi Hospitals Wichita
Wichita
Wesley Medical Center
Wichita
Kentucky
University of Kentucky/Markey Cancer Center
Lexington
Louisiana
Tulane University Health Sciences Center
New Orleans
Massachusetts
Tufts Medical Center
Boston
Lahey Hospital and Medical Center
Burlington
Lowell General Hospital
Lowell
Maryland
MedStar Union Memorial Hospital
Baltimore
University of Maryland/Greenebaum Cancer Center
Baltimore
UM Upper Chesapeake Medical Center
Bel Air
Central Maryland Radiation Oncology in Howard County
Columbia
UM Baltimore Washington Medical Center/Tate Cancer Center
Glen Burnie
UM Saint Joseph Medical Center
Towson
Michigan
Saint Joseph Mercy Hospital
Ann Arbor
McLaren Cancer Institute-Bay City
Bay City
Henry Ford Cancer Institute-Downriver
Brownstown
Saint Joseph Mercy Chelsea
Chelsea
21st Century Oncology MHP - Clarkston
Clarkston
McLaren Cancer Institute-Clarkston
Clarkston
Henry Ford Macomb Hospital-Clinton Township
Clinton Township
Henry Ford Hospital
Detroit
Wayne State University/Karmanos Cancer Institute
Detroit
21st Century Oncology MHP - Farmington
Farmington Hills
Genesys Hurley Cancer Institute
Flint
McLaren Cancer Institute-Flint
Flint
Spectrum Health at Butterworth Campus
Grand Rapids
West Michigan Cancer Center
Kalamazoo
McLaren Cancer Institute-Lapeer Region
Lapeer
Saint Mary Mercy Hospital
Livonia
McLaren Cancer Institute-Macomb
Mount Clemens
McLaren Cancer Institute-Central Michigan
Mount Pleasant
Mercy Health Mercy Campus
Muskegon
McLaren Cancer Institute-Owosso
Owosso
McLaren Cancer Institute-Northern Michigan
Petoskey
Saint Joseph Mercy Oakland
Pontiac
McLaren-Port Huron
Port Huron
Lakeland Medical Center Saint Joseph
Saint Joseph
21st Century Oncology MHP - Troy
Troy
Henry Ford West Bloomfield Hospital
West Bloomfield
Minnesota
Mayo Clinic Health System in Albert Lea
Albert Lea
Unity Hospital
Fridley
Mayo Clinic Health Systems-Mankato
Mankato
Abbott-Northwestern Hospital
Minneapolis
Mayo Clinic Radiation Therapy-Northfield
Northfield
Mayo Clinic
Rochester
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park
Missouri
Saint Francis Medical Center
Cape Girardeau
Siteman Cancer Center at West County Hospital
Creve Coeur
North Kansas City Hospital
Kansas City
Mercy Hospital Saint Louis
Saint Louis
Missouri Baptist Medical Center
Saint Louis
Siteman Cancer Center-South County
Saint Louis
Washington University School of Medicine
Saint Louis
Siteman Cancer Center at Saint Peters Hospital
Saint Peters
CoxHealth South Hospital
Springfield
Montana
Billings Clinic Cancer Center
Billings
Benefis Healthcare- Sletten Cancer Institute
Great Falls
Community Medical Hospital
Missoula
North Carolina
UNC Lineberger Comprehensive Cancer Center
Chapel Hill
NHRMC Radiation Oncology - 16th Street
Wilmington
North Dakota
Sanford Bismarck Medical Center
Bismarck
Sanford Roger Maris Cancer Center
Fargo
Nebraska
University of Nebraska Medical Center
Omaha
New Hampshire
Wentworth-Douglass Hospital
Dover
Dartmouth Hitchcock Medical Center
Lebanon
Nevada
Renown Regional Medical Center
Reno
New York
Montefiore Medical Center - Moses Campus
Bronx
New York-Presbyterian/Brooklyn Methodist Hospital
Brooklyn
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York
University of Rochester
Rochester
Ohio
Cleveland Clinic Akron General
Akron
Summa Akron City Hospital/Cooper Cancer Center
Akron
Case Western Reserve University
Cleveland
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland
Cleveland Clinic Foundation
Cleveland
Ohio State University Comprehensive Cancer Center
Columbus
Cleveland Clinic Cancer Center Independence
Independence
UH Seidman Cancer Center at Southwest General Hospital
Middleburg Heights
University Hospitals Parma Medical Center
Parma
Cleveland Clinic Cancer Center Strongsville
Strongsville
UHHS-Westlake Medical Center
Westlake
Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City
Oregon
Legacy Mount Hood Medical Center
Gresham
Legacy Good Samaritan Hospital and Medical Center
Portland
Pennsylvania
Abington Memorial Hospital
Abington
Crozer-Keystone Regional Cancer Center at Broomall
Broomall
Bryn Mawr Hospital
Bryn Mawr
Christiana Care Health System-Concord Health Center
Chadds Ford
Geisinger Medical Center
Danville
Northeast Radiation Oncology Center
Dunmore
Crozer Regional Cancer Center at Brinton Lake
Glen Mills
Riddle Memorial Hospital
Media
Aria Health-Torresdale Campus
Philadelphia
Fox Chase Cancer Center
Philadelphia
Temple University Hospital
Philadelphia
Thomas Jefferson University Hospital
Philadelphia
Reading Hospital
West Reading
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-barre
Lankenau Medical Center
Wynnewood
South Carolina
Greenville Health System Cancer Institute-Eastside
Greenville
Greenville Health System Cancer Institute-Faris
Greenville
Self Regional Healthcare
Greenwood
The Radiation Oncology Center-Hilton Head/Bluffton
Hilton Head Island
Greenville Health System Cancer Institute-Spartanburg
Spartanburg
South Dakota
Sanford USD Medical Center - Sioux Falls
Sioux Falls
Tennessee
Vanderbilt University/Ingram Cancer Center
Nashville
Texas
University of Texas Medical Branch
Galveston
M D Anderson Cancer Center
Houston
UTMB Cancer Center at Victory Lakes
League City
Utah
Ogden Regional Medical Center
Ogden
Huntsman Cancer Institute/University of Utah
Salt Lake City
Virginia
Virginia Commonwealth University/Massey Cancer Center
Richmond
Vermont
Norris Cotton Cancer Center-North
Saint Johnsbury
Washington
Virginia Mason Medical Center
Seattle
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
Yakima
Wisconsin
Langlade Hospital and Cancer Center
Antigo
Mayo Clinic Health System-Eau Claire Clinic
Eau Claire
Aurora Cancer Care-Grafton
Grafton
Aurora BayCare Medical Center
Green Bay
UW Cancer Center Johnson Creek
Johnson Creek
Aurora Cancer Care-Kenosha South
Kenosha
Gundersen Lutheran Medical Center
La Crosse
Mayo Clinic Health System-Franciscan Healthcare
La Crosse
University of Wisconsin Hospital and Clinics
Madison
Community Memorial Hospital
Menomonee Falls
Ascension Columbia Saint Mary's Water Tower Medical Commons
Milwaukee
Aurora Saint Luke's Medical Center
Milwaukee
Aurora Sinai Medical Center
Milwaukee
Medical College of Wisconsin
Milwaukee
Zablocki Veterans Administration Medical Center
Milwaukee
Vince Lombardi Cancer Clinic - Oshkosh
Oshkosh
Marshfield Clinic Stevens Point Center
Stevens Point
Aurora Medical Center in Summit
Summit
Vince Lombardi Cancer Clinic-Two Rivers
Two Rivers
Aspirus Regional Cancer Center
Wausau
Aurora West Allis Medical Center
West Allis
Diagnostic and Treatment Center
Weston
Aspirus UW Cancer Center
Wisconsin Rapids
West Virginia
West Virginia University Healthcare
Morgantown
Wheeling Hospital/Schiffler Cancer Center
Wheeling
Other Locations
Canada
CHUM - Centre Hospitalier de l'Universite de Montreal
Montreal
CHUM - Hopital Notre-Dame
Montreal
McGill University Department of Oncology
Montreal
The Research Institute of the McGill University Health Centre (MUHC)
Montreal
CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
Quebec City
Allan Blair Cancer Centre
Regina
Saskatoon Cancer Centre
Saskatoon
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke
Time Frame
Start Date: July 2015
Completion Date: August 26, 2019
Participants
Target number of participants: 518
Treatments
Experimental: WBRT + Memantine
Whole brain radiation therapy (WBRT) and memantine
Experimental: HA-WBRT/IMRT+ Memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) using intensity modulated radiation therapy (IMRT) and memantine
Authors
Steven J. Feigenberg, Nicholas A. Blondin, Olusola Obayomi-Davies, Clifford G. Robinson, Benjamin B. Bridges, John E. Mignano, Desiree E. Doncals, Timothy J. Kruser, Joseph W. Shelton, Vinai Gondi, Mitchell Machtay, Adam W. Nowlan, Jason R. Citron, Paul G. Montgomery, Matthew S. Katz, Richard A. Peterson, Preston D. Steen, Nayana L. Vora, Joseph W. Leach, Eric L. Chang, Evan J. Wuthrick, Yuhchyau Chen, Andrew Y. Kee, Jay W. Carlson, Mehmet S. Copur, Kalika P. Sarma, Anand Mahadevan, Arul Mahadevan, Scott G. Soltys, Sajeel A. Chowdhary, Wayne H. Pinover, Andrew O. Wahl, Steven P. Howard, Howard A. Zaren, Aaron W. Pederson, Thomas E. Lad, Christopher U. Jones, Patricia K. Lillis, Albert S. DeNittis, Gregory A. Masters, Keren Sturtz, Parvesh Kumar, Frank A. Vicini, Brian K. Chang, Kiran Devisetty, Joseph A. Bovi, Eleanor M. Walker, Joshua M. Mammen, Todd A. Swanson, Eric A. Mellon, Steven J. Dibiase, Malcolm D. Mattes, Wenyin Shi, Klaudia U. Hunter, Abhishek A. Solanki, Ellen L. Ziaja, Samir Narayan, David L. Grisell, Terrence P. Cescon, Elizabeth M. Gore, Steven J. Chmura, Collin D. Driscoll, Joshua D. Palmer, Chad G. Rusthoven, Shaker R. Dakhil, Dean J. Conterato, Samantha A. Seaward, Paul D. Brown, Alan C. Hartford, Ellen A. Wiegner, Michael A. Papagikos, Michael R. Girvigian, James C. Tucker, Jondavid Pollock, Pranshu Mohindra, Albert Attia, James L. Wade, Benjamin T. Marchello, Terence S. Herman, Jing Li, Mark V. Mishra, Darryl R. Barton, Brandon J. Fisher, Daniel W. Weed, Curtis T. Miyamoto, Paul B. Fowler, Esther H. Rehmus, Sameer Rafla-Demetrious, Joseph M. Jenrette, Tony J. Wang, Timothy J. Harris, Erin S. Murphy, Ronald C. McGarry, Jona A. Hattangadi-Gluth, Baldassarre Stea, Vijayananda Kundapur, Nagendra (Bobby) S. Koneru, David Roberge, Kathleen J. Yost, John A. Ellerton, Nadia N. Laack, Michelle J. Ferguson, John A. Keech, William R. Bodner
Sponsors
Leads: NRG Oncology
Collaborators: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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