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

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

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Impairment; Metastatic Malignant Neoplasm in the Brain; Solid Neoplasm
• Intervention / Treatment: Drug: Memantine; Radiation: Whole brain radiation therapy; Radiation: Whole brain radiation therapy with hippocampal avoidance

Detailed Description

PRIMARY OBJECTIVES:

I. Determine whether the addition of whole-brain radiotherapy with hippocampal avoidance (HA-WBRT) increases time to neurocognitive failure at months 2, 4, 6, and 12 as measured by neurocognitive decline on a battery of tests: the Hopkins Verbal Learning Test-Revised (HVLT-R) for Total Recall, Delayed Recall, and Delayed Recognition, Controlled Oral Word Association (COWA), and the Trail Making Test (TMT) Parts A and B.

SECONDARY OBJECTIVES:

I. Determine whether the addition of HA-WBRT preserves neurocognitive function at months 2, 4, 6, and 12 as separately measured by each test, the HVLT-R for Total Recall, Delayed Recall, and Delayed Recognition; COWA; and TMT Parts A and B.

II. Evaluate the potential benefit of HA-WBRT in symptom burden, as measured by the M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT).

III. Assessment of quality adjusted survival and cost analysis using the five-level version of the EuroQol five-dimensional (EQ-5D-5L).

IV. Compare cumulative incidence of progression and overall survival after WBRT versus HA-WBRT.

V. Compare adverse events between the treatment arms according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 criteria.

TERTIARY OBJECTIVES:

I. Collect serum, plasma, and imaging studies for future translational research analyses.

II. Evaluate magnetic resonance (MR) imaging biomarkers of white matter injury and hippocampal volumetry at baseline and 6 months as potential predictors of neurocognitive decline and differential benefit from HA-WBRT as compared to WBRT.

III. Association of symptom burden and anxiety/depression with neurocognitive function.

IV. Evaluate the potential correlation between the prognostic scoring systems Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) and the diagnosis-specific graded prognostic assessment (DS-GPA) and neurocognitive function at baseline and overtime.

After completion of study treatment, patients are followed up at 12 months.

• Study Type: Interventional
• Enrollment (Actual): 518
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3H 2R9
      • The Research Institute of the McGill University Health Centre (MUHC)
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University Department of Oncology
    • Montreal, Quebec, Canada, H2X 3E4
      • CHUM - Centre Hospitalier de l'Universite de Montreal
    • Quebec City, Quebec, Canada, G1R 2J6
      • CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35401
      • Lewis and Faye Manderson Cancer Center
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center - Tucson
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Carmichael, California, United States, 95608
      • Mercy San Juan Medical Center
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Los Angeles County-USC Medical Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Oakland, California, United States, 94611
      • Kaiser Permanente Oakland-Broadway
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
    • Rancho Cordova, California, United States, 95670
      • Kaiser Permanente-Rancho Cordova Cancer Center
    • Rohnert Park, California, United States, 94928
      • Rohnert Park Cancer Center
    • Roseville, California, United States, 95678
      • The Permanente Medical Group-Roseville Radiation Oncology
    • Roseville, California, United States, 95661
      • Sutter Cancer Centers Radiation Oncology Services-Roseville
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • Sacramento, California, United States, 95816
      • Mercy Cancer Center - Sacramento
    • San Diego, California, United States, 92103
      • University of California San Diego
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center-Pacific Campus
    • San Jose, California, United States, 95124
      • Stanford Cancer Center South Bay
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente Cancer Treatment Center
    • Vallejo, California, United States, 94589
      • Sutter Solano Medical Center/Cancer Center
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Rocky Mountain Cancer Centers-Boulder
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Colorado Springs, Colorado, United States, 80909
      • UCHealth Memorial Hospital Central
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Saint Vincent's Medical Center
  • Delaware
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital
    • Coral Gables, Florida, United States, 33146
      • UM Sylvester Comprehensive Cancer Center at Coral Gables
    • Deerfield Beach, Florida, United States, 33442
      • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Orlando, Florida, United States, 32806
      • UF Cancer Center at Orlando Health
    • Weston, Florida, United States, 33331
      • Cleveland Clinic-Weston
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30342
      • Emory Saint Joseph's Hospital
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Boise, Idaho, United States, 83712
      • Saint Luke's Mountain States Tumor Institute
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Mountain States Tumor Institute - Meridian
    • Nampa, Idaho, United States, 83686
      • Saint Luke's Mountain States Tumor Institute - Nampa
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Mountain States Tumor Institute-Twin Falls
  • Illinois
    • Carterville, Illinois, United States, 62918
      • SIH Cancer Institute
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Geneva, Illinois, United States, 60134
      • Northwestern Medicine Cancer Center Delnor
    • Hines, Illinois, United States, 60141
      • Edward Hines Jr VA Hospital
    • Libertyville, Illinois, United States, 60048
      • Condell Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Warrenville, Illinois, United States, 60555
      • Northwestern Medicine Cancer Center Warrenville
  • Indiana
    • Fort Wayne, Indiana, United States, 46805
      • Parkview Hospital Randallia
    • Indianapolis, Indiana, United States, 46219
      • Community Cancer Center East
    • Indianapolis, Indiana, United States, 46227
      • Community Cancer Center South
    • Indianapolis, Indiana, United States, 46256
      • Community Cancer Center North
  • Iowa
    • Cedar Rapids, Iowa, United States, 52402
      • Saint Luke's Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Overland Park, Kansas, United States, 66210
      • University of Kansas Cancer Center-Overland Park
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Baltimore, Maryland, United States, 21218
      • MedStar Union Memorial Hospital
    • Bel Air, Maryland, United States, 21014
      • UM Upper Chesapeake Medical Center
    • Columbia, Maryland, United States, 21044
      • Central Maryland Radiation Oncology in Howard County
    • Glen Burnie, Maryland, United States, 21061
      • UM Baltimore Washington Medical Center/Tate Cancer Center
    • Towson, Maryland, United States, 21204
      • UM Saint Joseph Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
    • Lowell, Massachusetts, United States, 01854
      • Lowell General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Bay City, Michigan, United States, 48706
      • McLaren Cancer Institute-Bay City
    • Brownstown, Michigan, United States, 48183
      • Henry Ford Cancer Institute-Downriver
    • Chelsea, Michigan, United States, 48118
      • Saint Joseph Mercy Chelsea
    • Clarkston, Michigan, United States, 48346
      • McLaren Cancer Institute-Clarkston
    • Clarkston, Michigan, United States, 48346
      • 21st Century Oncology MHP - Clarkston
    • Clinton Township, Michigan, United States, 48038
      • Henry Ford Macomb Hospital-Clinton Township
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Farmington Hills, Michigan, United States, 48334
      • 21st Century Oncology MHP - Farmington
    • Flint, Michigan, United States, 48532
      • McLaren Cancer Institute-Flint
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Lapeer, Michigan, United States, 48446
      • McLaren Cancer Institute-Lapeer Region
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Mount Clemens, Michigan, United States, 48043
      • McLaren Cancer Institute-Macomb
    • Mount Pleasant, Michigan, United States, 48858
      • McLaren Cancer Institute-Central Michigan
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Owosso, Michigan, United States, 48867
      • McLaren Cancer Institute-Owosso
    • Petoskey, Michigan, United States, 49770
      • McLaren Cancer Institute-Northern Michigan
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • McLaren-Port Huron
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center Saint Joseph
    • Troy, Michigan, United States, 48098
      • 21st Century Oncology MHP - Troy
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
  • Minnesota
    • Albert Lea, Minnesota, United States, 56007
      • Mayo Clinic Health System in Albert Lea
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Mankato, Minnesota, United States, 56001
      • Mayo Clinic Health Systems-Mankato
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Northfield, Minnesota, United States, 55057
      • Mayo Clinic Radiation Therapy-Northfield
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Missoula, Montana, United States, 59804
      • Community Medical Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
  • New Hampshire
    • Dover, New Hampshire, United States, 03820
      • Wentworth-Douglass Hospital
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Campus
    • Brooklyn, New York, United States, 11215
      • New York-Presbyterian/Brooklyn Methodist Hospital
    • New York, New York, United States, 10032
      • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Wilmington, North Carolina, United States, 28401
      • NHRMC Radiation Oncology - 16th Street
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Roger Maris Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • Cleveland Clinic Akron General
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital/Cooper Cancer Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center Independence
    • Middleburg Heights, Ohio, United States, 44130
      • UH Seidman Cancer Center at Southwest General Hospital
    • Parma, Ohio, United States, 44129
      • University Hospitals Parma Medical Center
    • Strongsville, Ohio, United States, 44136
      • Cleveland Clinic Cancer Center Strongsville
    • Westlake, Ohio, United States, 44145
      • UHHS-Westlake Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital and Medical Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Broomall, Pennsylvania, United States, 19008
      • Crozer-Keystone Regional Cancer Center at Broomall
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Chadds Ford, Pennsylvania, United States, 19317
      • Christiana Care Health System-Concord Health Center
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Dunmore, Pennsylvania, United States, 18512
      • Northeast Radiation Oncology Center
    • Glen Mills, Pennsylvania, United States, 19342
      • Crozer Regional Cancer Center at Brinton Lake
    • Media, Pennsylvania, United States, 19063
      • Riddle Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 19114
      • Aria Health-Torresdale Campus
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Faris
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Institute-Eastside
    • Greenwood, South Carolina, United States, 29646
      • Self Regional Healthcare
    • Hilton Head Island, South Carolina, United States, 29926
      • The Radiation Oncology Center-Hilton Head/Bluffton
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System Cancer Institute-Spartanburg
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
  • Texas
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • League City, Texas, United States, 77573
      • UTMB Cancer Center at Victory Lakes
  • Utah
    • Ogden, Utah, United States, 84405
      • Ogden Regional Medical Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Vermont
    • Saint Johnsbury, Vermont, United States, 05819
      • Norris Cotton Cancer Center-North
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Healthcare
    • Wheeling, West Virginia, United States, 26003
      • Wheeling Hospital/Schiffler Cancer Center
  • Wisconsin
    • Antigo, Wisconsin, United States, 54409
      • Langlade Hospital and Cancer Center
    • Eau Claire, Wisconsin, United States, 54701
      • Mayo Clinic Health System-Eau Claire Clinic
    • Grafton, Wisconsin, United States, 53024
      • Aurora Cancer Care-Grafton
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center
    • Johnson Creek, Wisconsin, United States, 53038
      • UW Cancer Center Johnson Creek
    • Kenosha, Wisconsin, United States, 53142
      • Aurora Cancer Care-Kenosha South
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • La Crosse, Wisconsin, United States, 54601
      • Mayo Clinic Health System-Franciscan Healthcare
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Menomonee Falls, Wisconsin, United States, 53051
      • Community Memorial Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Sinai Medical Center
    • Milwaukee, Wisconsin, United States, 53295
      • Zablocki Veterans Administration Medical Center
    • Milwaukee, Wisconsin, United States, 53211
      • Ascension Columbia Saint Mary's Water Tower Medical Commons
    • Oshkosh, Wisconsin, United States, 54904
      • Vince Lombardi Cancer Clinic - Oshkosh
    • Stevens Point, Wisconsin, United States, 54482
      • Marshfield Clinic Stevens Point Center
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center in Summit
    • Two Rivers, Wisconsin, United States, 54241
      • Vince Lombardi Cancer Clinic-Two Rivers
    • Wausau, Wisconsin, United States, 54401
      • Aspirus Regional Cancer Center
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center
    • Weston, Wisconsin, United States, 54476
      • Diagnostic and Treatment Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Aspirus UW Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WBRT + Memantine; Whole brain radiation therapy (WBRT) and memantine	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.; Other Names: Namenda; Ebixia; Memantine Hydrochloride; 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; Other Names: WBRT; whole-brain radiation therapy; whole-brain radiotherapy
Experimental: HA-WBRT/IMRT+ Memantine; Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) using intensity modulated radiation therapy (IMRT) and memantine	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.; Other Names: Namenda; Ebixia; Memantine Hydrochloride; 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.; Other Names: IMRT; Intensity Modulated RT; INTENSITY-MODULATED RADIATION THERAPY; Intensity-Modulated Radiotherapy; WBRT; whole-brain radiotherapy; Whole-brain radiation therapy; HA-WBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Neurocognitive Failure	Neurocognitive failure is defined as the first failure, defined as a neurocognitive decline using the reliable change index (RCI) on at least one of the following assessments or parts of : Hopkins Verbal Learning Test - Revised (HVLT-R), Trail Making Test (TMT), or Controlled Oral Word Association (COWA). The HVLT-R has 3 parts that were analyzed separately for decline: Total Recall, Delayed Recall, and Delayed Recognition. The TMT has 2 parts that were analyzed separately: Part A and Part B. Neurocognitive failure rate is estimated using the cumulative incidence method. Analysis was planned to occur after 233 events were reported. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Six-month rates are provided.Analysis was planned to occur after 233 events were reported.	From randomization to last follow-up. Maximum follow-up was 15.6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall Score (Neurocognitive Decline)	The HVLT-R assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials (Total Recall), recalling the 12 targets after a 20-minute delay (Delayed Recall), and then identifying the 12 targets from a list of semantically related or unrelated items (delayed recognition). Raw scores are derived for total recall (sum of the number of targets correctly recalled), delayed recall (sum of the number of targets correctly recalled), and a delayed recognition discrimination index (sum of targets incorrectly identified subtracted from the sum of the number of targets correctly identified). The range of scores for total recall is 0 to 36, for delayed recall is 0 to 12, and -12 to 12 for recognition. A higher score indicates better functioning. Scores are standardized, adjusting for age, education, and gender as necessary, such that mean 0 and standard deviation is 1. Change is calculated as baseline score subtracted from post-baseline score.	Baseline, 2, 4, 6, and 12 months
Change From Baseline in the Hopkins Verbal Learning Test -Revised (HVLT-R) Delayed Recall Score (Neurocognitive Decline)	The HVLT-R assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials (Total Recall), recalling the 12 targets after a 20-minute delay (Delayed Recall), and then identifying the 12 targets from a list of semantically related or unrelated items (delayed recognition). Raw scores are derived for total recall (sum of the number of targets correctly recalled), delayed recall (sum of the number of targets correctly recalled), and a delayed recognition discrimination index (sum of targets incorrectly identified subtracted from the sum of the number of targets correctly identified). The range of scores for total recall is 0 to 36, for delayed recall is 0 to 12, and -12 to 12 for recognition. A higher score indicates better functioning. Scores are standardized, adjusting for age, education, and gender as necessary, such that mean 0 and standard deviation is 1. Change is calculated as baseline score subtracted from post-baseline score.	Baseline, 2, 4, 6, and 12 months
Change From Baseline in the Hopkins Verbal Learning Test -Revised (HVLT-R) Delayed Recognition (Neurocognitive Decline)	The HVLT-R assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials (Total Recall), recalling the 12 targets after a 20-minute delay (Delayed Recall), and then identifying the 12 targets from a list of semantically related or unrelated items (delayed recognition). Raw scores are derived for total recall (sum of the number of targets correctly recalled), delayed recall (sum of the number of targets correctly recalled), and a delayed recognition discrimination index (sum of targets incorrectly identified subtracted from the sum of the number of targets correctly identified). The range of scores for total recall is 0 to 36, for delayed recall is 0 to 12, and -12 to 12 for recognition. A higher score indicates better functioning. Scores are standardized by expressing the deviation from the mean score of the group in units of standard deviation. Change is calculated as baseline score subtracted from post-baseline score.	Baseline, 2, 4, 6, and 12 months
Change From Baseline in the Trail Making Test (TMT) Part A (Neurocognitive Decline)	The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the first (Part A), the targets are all numbers (1, 2, 3, etc.) and the test taker needs to connect them in sequential order; in the second part (Part B), the subject alternates between numbers and letters (1, A, 2, B, etc.). The score is the amount of time, in seconds, that it takes the patient to complete each maze. The range for Part A is 0 to 180 (3 minutes) and for Part B is 0 to 300 (5 minutes). Lower scores indicate better functioning. Scores are standardized, adjusting for age, education, gender as needed, so that mean is 0 and standard deviation is 1. Change is calculated as baseline score subtracted from post-baseline score.	Baseline, 2, 4, 6, and 12 months
Change From Baseline in the Trail Making Test (TMT) Part B (Neurocognitive Decline)	The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the first (Part A), the targets are all numbers (1, 2, 3, etc.) and the test taker needs to connect them in sequential order; in the second part (Part B), the subject alternates between numbers and letters (1, A, 2, B, etc.). The score is the amount of time, in seconds, that it takes the patient to complete each maze. The range for Part A is 0 to 180 (3 minutes) and for Part B is 0 to 300 (5 minutes). A lower score indicates better functioning. Scores are standardized by expressing the deviation from the mean score of the group in units of standard deviation. Change is calculated as baseline score subtracted from post-baseline score.	Baseline, 2, 4, 6, and 12 months
Change From Baseline in the Controlled Oral Word Association (COWA) Test (Neurocognitive Decline)	The COWA is a verbal fluency test that measures spontaneous production of words belonging to the same category or beginning with some designated letter. Patients are given 1 minute to name as many words as possible beginning with the designated letter. The procedure is then repeated for the remaining two letters. Two alternate forms of the COWA are employed to minimize practice effects. The score is the sum of the correct responses with a range of 0 to infinity. A higher score indicates better functioning. Scores are standardized, adjusting for age, education, and gender as necessary, such that mean is 0 and standard deviation is 1. Change is calculated as baseline score subtracted from post-baseline score.	Baseline, 2, 4, 6, and 12 months
Change From Baseline in the Clinical Trial Battery Composite (CTB COMP) Score [Neurocognitive Decline]	Clinical Trial Battery Composite score is the arithmetic mean of the HVLT-R (Free Recall, Delayed Recall, Delayed Recognition), TMTA, TMTB, and COWA scores, all of which are standardized, adjusting for age, education, and gender as necessary, such that mean is 0 and standard deviation is 1. A participant must have at least 5 of the 6 scores. A higher composite score indicates better neurocognitive function.Change is calculated as baseline score subtracted from post-baseline score.	Baseline, 2, 4, 6, and 12 months
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score	The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score (Symptom Severity) is the average of the subscale items, given that a specified minimum numbers of items were completed.	Baseline, 2, 4, 6, and 12 months
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Interference Score	The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score (Interference) is the average of the subscale items, given that a specified minimum numbers of items were completed.	Baseline, 2, 4, 6, and 12 months
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Factor Score	The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score (Cognitive Factor) is the average of the subscale items, given that a specified minimum numbers of items were completed.	Baseline, 2, 4, 6, and 12 months
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Neurologic Factor Score	The MD Anderson Symptom Inventory for brain tumor (MDASI-BT) is a 28-item multi-symptom patient-reported outcome measure assessing the severity of symptoms experienced by cancer patients and the interference with daily living caused by these symptoms, with 9 items specific to brain tumors. Each item ranges from 0 (best condition) to 10 (worst condition). A subscale score (Neurologic Factor) is the average of the subscale items, given that a specified minimum numbers of items were completed.	Baseline, 2, 4, 6, and 12 months
Change in EQ-5D-5L Index Score at 2 Months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The index score is reported here.	Baseline and 2 months
Change in EQ-5D-5L Index Score at 4 Months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The index score is reported here.	Baseline and 4 months
Change in EQ-5D-5L Index Score at 6 Months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The index score is reported here.	Baseline and 6 months
Change in EQ-5D-5L Index Score at 12 Months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The index score is reported here.	Baseline and 12 months
Change in EQ-5D-5L VAS Score at 2 Months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The VAS score is reported here.	Baseline and 2 months
Change in EQ-5D-5L VAS Score at 4 Months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The VAS score is reported here.	Baseline and 4 months
Change in EQ-5D-5L VAS Score at 6 Months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The VAS score is reported here.	Baseline and 6 months
Change in EQ-5D-5L VAS Score at 12 Months	The EQ-5D-5L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The VAS score is reported here.	Baseline and 12 months
Intracranial Progression-Free Survival	Intracranial progression-free survival time is defined as time from registration/randomization to the date of progression in the brain or death from any cause. Intracranial progression-free survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Analysis was planned to occur after 233 primary endpoint events (neurocognitive failure) were reported. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Six-month rates are provided.	From randomization to last follow-up. Analysis was planned to occur after 233 events were reported. Maximum follow-up was 15.6 months.
Overall Survival	Overall survival time is defined as time from registration/randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Analysis was planned to occur after 233 primary endpoint events (neurocognitive failure) were reported. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Six-month rates are provided.	From randomization to last follow-up. Maximum follow-up was 15.6 months.
Number of Patients With a Grade 3+ Adverse Event (AE) Regardless of Relationship to Treatment	. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.	From randomization to last follow-up. Analysis was planned to occur after 233 events were reported. Maximum follow-up was 15.6 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anxiety/Depression Measured Using the EQ-5D-5L	An exploratory analysis, beginning with correlation coefficients, will be used to assess the association of symptom burden and anxiety/depression with neurocognitive function at each time point. The symptom burden items of interest are the "distressed (upset)", "sad", and "mood" items. From the EQ-5D-5L, the depression/anxiety item will be of interest.	Up to 12 months
Effect of Radiation Therapy Oncology Group (RTOG) RPA and the Diagnosis-specific Graded Prognostic Assessment (DSGPA) on Neurocognitive Function	Neurocognitive function, as measured by the HVLT-R, COWA, and TMT, will be correlated with both the RTOG RPA and the DS-GPA classification systems. Baseline neurocognitive function for each test will be compared between both RPA classes using either a t-test or Wilcoxon-Mann-Whitney test, depending on the normality of the data.	Up to 12 months
Effect of White Matter Injury and Hippocampal Volume on Neurocognitive Function	Evaluated through MRI scans using physician-contoured and auto-contoured scores. Concordance rates will be assessed using Kappa statistics. The auto-contoured scores will be used for the remaining analyses due to the number of physicians reviewing the scans. White matter injury is measured by FLAIR volume change and is a continuous variable. Hippocampal volume is measured as a continuous variable also and both will be covariates considered in the Cox proportional hazards model to assess the impact on time to neurocognitive failure and the longitudinal modeling of neurocognitive function.	Up to 12 months
MDASI-BT Mood Variables	The relationship between EQ-5D-5L and MDASI-BT mood variables and neurocognitive function will be assessed.	Up to 12 months

Collaborators and Investigators

• Sponsor: NRG Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Paul Brown, NRG Oncology

Publications and helpful links

General Publications

• Brown PD, Gondi V, Pugh S, Tome WA, Wefel JS, Armstrong TS, Bovi JA, Robinson C, Konski A, Khuntia D, Grosshans D, Benzinger TLS, Bruner D, Gilbert MR, Roberge D, Kundapur V, Devisetty K, Shah S, Usuki K, Anderson BM, Stea B, Yoon H, Li J, Laack NN, Kruser TJ, Chmura SJ, Shi W, Deshmukh S, Mehta MP, Kachnic LA; for NRG Oncology. Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001. J Clin Oncol. 2020 Apr 1;38(10):1019-1029. doi: 10.1200/JCO.19.02767. Epub 2020 Feb 14.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): April 30, 2018
• Study Completion (Actual): August 26, 2019

Study Registration Dates

• First Submitted: February 5, 2015
• First Submitted That Met QC Criteria: February 5, 2015
• First Posted (Estimate): February 10, 2015

Study Record Updates

• Last Update Posted (Actual): June 2, 2021
• Last Update Submitted That Met QC Criteria: May 12, 2021
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms; Brain Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: NRG-CC001 (Other Identifier: CTEP); UG1CA189867 (U.S. NIH Grant/Contract); NCI-2015-00030 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: NCT02360215
   Information comments: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No