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COMPLETED

NCT02360215

PHASE3

Memantine Hydrochloride and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Reducing Neurocognitive Decline in Patients With Brain Metastases

Sponsor: NRG Oncology

View on ClinicalTrials.gov

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.

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

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

518

Start Date

2015-07

Completion Date

2019-08-26

Last Updated

2026-09-10

Healthy Volunteers

Conditions

Cognitive Impairment Metastatic Malignant Neoplasm in the Brain Solid Neoplasm

Interventions

RADIATION

Whole brain radiation therapy with hippocampal avoidance

Intensity modulated radiation therapy (IMRT) 30 Gy in 10 fractions once per day, 5 days per week for approximately two week; starting within 21 calendar days after randomization.

DRUG

Memantine

Given PO daily during and after radiation therapy for a total of 24 weeks. Week 1: 5 mg in the AM, none in the PM; Week 2: 5 mg in the AM, 5 mg in the PM; Week 3: 10 mg in the AM, 5 mg in the PM; Weeks 4-24: 10 mg in the AM, 10 mg in the PM. Should start the same day as radiation therapy, at latest before the fourth radiation treatment.

RADIATION

Whole brain radiation therapy

Whole brain radiation therapy (WBRT) 30 Gy in 10 fractions once per day, 5 days per week for approximately 2 weeks

Inclusion Criteria: * 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 Exclusion Criteria: * Prior external beam radiation therapy to the brain or whole brain radiation therapy * Planned cytotoxic chemotherapy during the WBRT only; patients may have had prior chemotherapy * Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt * 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 registration * Chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy at the time of registration * Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic disease * Renal tubular acidosis or metabolic acidosis * Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count \< 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count \>= 200 cells/microliter within 30 days prior to registration; Note also that HIV testing is not required for eligibility for this protocol * Pregnant or lactating women, or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception * Prior allergic reaction to memantine (memantine hydrochloride) * Current alcohol or drug abuse (may exacerbate lethargy/dizziness with memantine) * Intractable seizures while on adequate anticonvulsant therapy-more than 1 seizure per month for the past 2 months * Patients with definitive leptomeningeal metastases * Patients with brain metastases from primary germ cell tumors, small cell carcinoma, unknown primary, or lymphoma * Contraindication to magnetic resonance (MR) imaging such as implanted metal devices or foreign bodies * Contraindication to gadolinium contrast administration during MR imaging, such as allergy or insufficient renal function * Current use of (other N-methyl D-aspartate \[NMDA\] antagonists) amantadine, ketamine, or dextromethorphan

Locations (220)

Lewis and Faye Manderson Cancer Center

Tuscaloosa, Alabama, United States

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Banner University Medical Center - Tucson

Tucson, Arizona, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, United States

Mercy San Juan Medical Center

Carmichael, California, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

UC San Diego Moores Cancer Center

La Jolla, California, United States

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Los Angeles County-USC Medical Center

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Kaiser Permanente Oakland-Broadway

Oakland, California, United States

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Kaiser Permanente-Rancho Cordova Cancer Center

Rancho Cordova, California, United States

Rohnert Park Cancer Center

Rohnert Park, California, United States

Sutter Cancer Centers Radiation Oncology Services-Roseville

Roseville, California, United States

The Permanente Medical Group-Roseville Radiation Oncology

Roseville, California, United States

Mercy Cancer Center - Sacramento

Sacramento, California, United States

Sutter Medical Center Sacramento

Sacramento, California, United States

University of California San Diego

San Diego, California, United States

California Pacific Medical Center-Pacific Campus

San Francisco, California, United States

Stanford Cancer Center South Bay

San Jose, California, United States

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, United States

Kaiser Permanente Cancer Treatment Center

South San Francisco, California, United States

Sutter Solano Medical Center/Cancer Center

Vallejo, California, United States

Rocky Mountain Cancer Centers-Boulder

Boulder, Colorado, United States

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States

UCHealth Memorial Hospital Central

Colorado Springs, Colorado, United States

Swedish Medical Center

Englewood, Colorado, United States

Saint Vincent's Medical Center

Bridgeport, Connecticut, United States

Helen F Graham Cancer Center

Newark, Delaware, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Boca Raton Regional Hospital

Boca Raton, Florida, United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

UF Cancer Center at Orlando Health

Orlando, Florida, United States

Cleveland Clinic-Weston

Weston, Florida, United States

Grady Health System

Atlanta, Georgia, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Piedmont Hospital

Atlanta, Georgia, United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Emory Saint Joseph's Hospital

Atlanta, Georgia, United States

Memorial Health University Medical Center

Savannah, Georgia, United States

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

Savannah, Georgia, United States

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, United States

Saint Luke's Mountain States Tumor Institute

Boise, Idaho, United States

Saint Luke's Mountain States Tumor Institute - Meridian

Meridian, Idaho, United States

Saint Luke's Mountain States Tumor Institute - Nampa

Nampa, Idaho, United States

Saint Luke's Mountain States Tumor Institute-Twin Falls

Twin Falls, Idaho, United States

SIH Cancer Institute

Carterville, Illinois, United States

Northwestern University

Chicago, Illinois, United States

John H Stroger Jr Hospital of Cook County

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Decatur Memorial Hospital

Decatur, Illinois, United States

Crossroads Cancer Center

Effingham, Illinois, United States

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, United States

Edward Hines Jr VA Hospital

Hines, Illinois, United States

Condell Memorial Hospital

Libertyville, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

Methodist Medical Center of Illinois

Peoria, Illinois, United States

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Memorial Medical Center

Springfield, Illinois, United States

Carle Cancer Center

Urbana, Illinois, United States

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States

Parkview Hospital Randallia

Fort Wayne, Indiana, United States

Community Cancer Center East

Indianapolis, Indiana, United States

Community Cancer Center South

Indianapolis, Indiana, United States

Community Cancer Center North

Indianapolis, Indiana, United States

Saint Luke's Hospital

Cedar Rapids, Iowa, United States

University of Kansas Cancer Center

Kansas City, Kansas, United States

Lawrence Memorial Hospital

Lawrence, Kansas, United States

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, United States

Ascension Via Christi Hospitals Wichita

Wichita, Kansas, United States

Wesley Medical Center

Wichita, Kansas, United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

MedStar Union Memorial Hospital

Baltimore, Maryland, United States

UM Upper Chesapeake Medical Center

Bel Air, Maryland, United States

Central Maryland Radiation Oncology in Howard County

Columbia, Maryland, United States

UM Baltimore Washington Medical Center/Tate Cancer Center

Glen Burnie, Maryland, United States

UM Saint Joseph Medical Center

Towson, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Lowell General Hospital

Lowell, Massachusetts, United States

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

McLaren Cancer Institute-Bay City

Bay City, Michigan, United States

Henry Ford Cancer Institute-Downriver

Brownstown, Michigan, United States

Saint Joseph Mercy Chelsea

Chelsea, Michigan, United States

21st Century Oncology MHP - Clarkston

Clarkston, Michigan, United States

McLaren Cancer Institute-Clarkston

Clarkston, Michigan, United States

Henry Ford Macomb Hospital-Clinton Township

Clinton Township, Michigan, United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

21st Century Oncology MHP - Farmington

Farmington Hills, Michigan, United States

Genesys Hurley Cancer Institute

Flint, Michigan, United States

McLaren Cancer Institute-Flint

Flint, Michigan, United States

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

McLaren Cancer Institute-Lapeer Region

Lapeer, Michigan, United States

Saint Mary Mercy Hospital

Livonia, Michigan, United States

McLaren Cancer Institute-Macomb

Mount Clemens, Michigan, United States

McLaren Cancer Institute-Central Michigan

Mount Pleasant, Michigan, United States

Mercy Health Mercy Campus

Muskegon, Michigan, United States

McLaren Cancer Institute-Owosso

Owosso, Michigan, United States

McLaren Cancer Institute-Northern Michigan

Petoskey, Michigan, United States

Saint Joseph Mercy Oakland

Pontiac, Michigan, United States

McLaren-Port Huron

Port Huron, Michigan, United States

Lakeland Medical Center Saint Joseph

Saint Joseph, Michigan, United States

21st Century Oncology MHP - Troy

Troy, Michigan, United States

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, United States

Mayo Clinic Health System in Albert Lea

Albert Lea, Minnesota, United States

Unity Hospital

Fridley, Minnesota, United States

Mayo Clinic Health Systems-Mankato

Mankato, Minnesota, United States

Abbott-Northwestern Hospital

Minneapolis, Minnesota, United States

Mayo Clinic Radiation Therapy-Northfield

Northfield, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, United States

Saint Francis Medical Center

Cape Girardeau, Missouri, United States

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, United States

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, United States

North Kansas City Hospital

Kansas City, Missouri, United States

CoxHealth South Hospital

Springfield, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Siteman Cancer Center-South County

St Louis, Missouri, United States

Missouri Baptist Medical Center

St Louis, Missouri, United States

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Billings Clinic Cancer Center

Billings, Montana, United States

Benefis Healthcare- Sletten Cancer Institute

Great Falls, Montana, United States

Community Medical Hospital

Missoula, Montana, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Renown Regional Medical Center

Reno, Nevada, United States

Wentworth-Douglass Hospital

Dover, New Hampshire, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

New York-Presbyterian/Brooklyn Methodist Hospital

Brooklyn, New York, United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

University of Rochester

Rochester, New York, United States

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

NHRMC Radiation Oncology - 16th Street

Wilmington, North Carolina, United States

Sanford Bismarck Medical Center

Bismarck, North Dakota, United States

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, United States

Cleveland Clinic Akron General

Akron, Ohio, United States

Case Western Reserve University

Cleveland, Ohio, United States

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Cleveland Clinic Cancer Center Independence

Independence, Ohio, United States

UH Seidman Cancer Center at Southwest General Hospital

Middleburg Heights, Ohio, United States

University Hospitals Parma Medical Center

Parma, Ohio, United States

Cleveland Clinic Cancer Center Strongsville

Strongsville, Ohio, United States

UHHS-Westlake Medical Center

Westlake, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Legacy Mount Hood Medical Center

Gresham, Oregon, United States

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, United States

Abington Memorial Hospital

Abington, Pennsylvania, United States

Crozer-Keystone Regional Cancer Center at Broomall

Broomall, Pennsylvania, United States

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, United States

Christiana Care Health System-Concord Health Center

Chadds Ford, Pennsylvania, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Northeast Radiation Oncology Center

Dunmore, Pennsylvania, United States

Crozer Regional Cancer Center at Brinton Lake

Glen Mills, Pennsylvania, United States

Riddle Memorial Hospital

Media, Pennsylvania, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Aria Health-Torresdale Campus

Philadelphia, Pennsylvania, United States

Temple University Hospital

Philadelphia, Pennsylvania, United States

Reading Hospital

West Reading, Pennsylvania, United States

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania, United States

Lankenau Medical Center

Wynnewood, Pennsylvania, United States

Greenville Health System Cancer Institute-Faris

Greenville, South Carolina, United States

Greenville Health System Cancer Institute-Eastside

Greenville, South Carolina, United States

Self Regional Healthcare

Greenwood, South Carolina, United States

The Radiation Oncology Center-Hilton Head/Bluffton

Hilton Head Island, South Carolina, United States

Greenville Health System Cancer Institute-Spartanburg

Spartanburg, South Carolina, United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

University of Texas Medical Branch

Galveston, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

UTMB Cancer Center at Victory Lakes

League City, Texas, United States

Ogden Regional Medical Center

Ogden, Utah, United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Norris Cotton Cancer Center-North

Saint Johnsbury, Vermont, United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Virginia Mason Medical Center

Seattle, Washington, United States

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington, United States

West Virginia University Healthcare

Morgantown, West Virginia, United States

Wheeling Hospital/Schiffler Cancer Center

Wheeling, West Virginia, United States

Langlade Hospital and Cancer Center

Antigo, Wisconsin, United States

Mayo Clinic Health System-Eau Claire Clinic

Eau Claire, Wisconsin, United States

Aurora Cancer Care-Grafton

Grafton, Wisconsin, United States

Aurora BayCare Medical Center

Green Bay, Wisconsin, United States

UW Cancer Center Johnson Creek

Johnson Creek, Wisconsin, United States

Aurora Cancer Care-Kenosha South

Kenosha, Wisconsin, United States

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States

Mayo Clinic Health System-Franciscan Healthcare

La Crosse, Wisconsin, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Community Memorial Hospital

Menomonee Falls, Wisconsin, United States

Ascension Columbia Saint Mary's Water Tower Medical Commons