Memantine in Preventing Side Effects in Patients Undergoing Whole-Brain Radiation Therapy for Brain Metastases From Solid Tumors

A Randomized, Phase III, Double-Blind, Placebo-Controlled Trial of Memantine for Prevention of Cognitive Dysfunction in Patients Receiving Whole-Brain Radiotherapy

RATIONALE: Memantine may be able to decrease side effects caused by whole-brain radiation therapy. It is not yet known if memantine is effective in preventing side effects caused by whole-brain radiation therapy.

PURPOSE: This randomized phase III trial is studying memantine to see how well it works compared to a placebo in preventing side effects caused by whole-brain radiation therapy in patients with brain metastases from solid tumors.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Metastatic Cancer; Neurotoxicity; Cognitive/Functional Effects
• Intervention / Treatment: Drug: Memantine; Radiation: Whole brain radiation therapy; Other: Placebo

Detailed Description

OBJECTIVES:

Primary

• Determine whether the addition of memantine hydrochloride to whole-brain radiotherapy (WBRT) preserves cognitive function, specifically memory, as measured by the Hopkins Verbal Learning Test for delayed recall (HVLT-delayed recall), over that of placebo and WBRT in patients with brain metastases at 24 weeks from the start of drug treatment.

Secondary

• Determine whether the addition of memantine hydrochloride preserves cognitive function, specifically memory, as measured by the HVLT-delayed recall at 8 weeks, 16 weeks, and 12 months from the start of drug treatment.
• Determine whether the addition of memantine hydrochloride increases time to neurocognitive failure as measured by cognitive decline on a battery of tests including the HVLT for free recall, delayed recall, and delayed recognition; the Controlled Word Association Test (COWAT); the Trail Making Test Parts A and B (TMT); the Medical Outcomes Scale-Cognitive Functioning Subscale (MOS); and the Mini-Mental Status Examination (MMSE).
• Evaluate the potential benefit of memantine hydrochloride in change and overall quality of life, as measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) subscale.
• Determine whether the addition of memantine hydrochloride increases progression-free survival.
• Determine whether the addition of memantine hydrochloride increases overall survival.
• Compare adverse events between the treatment arms according to the CTCAE v3.0 criteria.
• Collect serum, plasma, buffy coat cells, urine, and cerebrospinal fluid (CSF) for future translational research analyses.

OUTLINE: This is a multicenter study. Patients are stratified according to recursive partitioning analysis (RPA) prognostic class (class I vs class II with controlled systemic disease) and prior surgical therapy (none vs radiosurgery or surgical resection). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo whole-brain radiotherapy (WBRT) 5 days a week for 3 weeks (15 fractions). Patients also receive oral memantine hydrochloride once daily beginning on day 1 of WBRT and continuing for 24 weeks.
• Arm II: Patients undergo WBRT as in arm I. Patients also receive oral placebo once daily beginning on day 1 of WBRT and continuing for 24 weeks.

After completion of study treatment, patients are followed at 6 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

• Study Type: Interventional
• Enrollment (Actual): 554
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V8
      • Nova Scotia Cancer Centre
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program at London Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill Cancer Centre at McGill University
    • Montreal, Quebec, Canada, H2L 4M1
      • Hopital Notre-Dame du CHUM
    • Quebec City, Quebec, Canada, G1R 2J6
      • Centre Hospitalier Universitaire de Quebec
• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • MBCCOP - Gulf Coast
    • Mobile, Alabama, United States, 36608
      • Providence Cancer Center at Providence Hospital
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Arizona Oncology Services Foundation
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
    • Tucson, Arizona, United States, 85704
      • Arizona Oncology - Tucson
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center at University of Arizona Health Sciences Center
  • California
    • Auburn, California, United States, 95603
      • Auburn Radiation Oncology
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center - Burbank
    • Cameron Park, California, United States, 95682
      • Radiation Oncology Centers - Cameron Park
    • Carmichael, California, United States, 95608
      • Mercy Cancer Center at Mercy San Juan Medical Center
    • Chico, California, United States, 95926
      • Enloe Cancer Center at Enloe Medical Center
    • Concord, California, United States, 94524-4110
      • Cancer Care Center at John Muir Health - Concord Campus
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • Glendale, California, United States, 91206
      • Glendale Adventist Medical Center
    • La Jolla, California, United States, 92093-0658
      • Rebecca and John Moores UCSD Cancer Center
    • Los Angeles, California, United States, 90089-9181
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Los Angeles, California, United States, 90048
      • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
    • Orange, California, United States, 92868
      • St. Joseph Hospital Regional Cancer Center - Orange
    • Roseville, California, United States, 95661
      • Radiation Oncology Center - Roseville
    • Sacramento, California, United States, 95815
      • Radiological Associates of Sacramento Medical Group, Incorporated
    • Sacramento, California, United States, 95819
      • Mercy General Hospital
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • Stanford, California, United States, 94305-5824
      • Stanford Cancer Center
    • Turlock, California, United States, 95382
      • Emanuel Regional Cancer Services at Emanuel Medical Center
    • Vacaville, California, United States, 95687
      • Solano Radiation Oncology Center
    • Walnut Creek, California, United States, 94598
      • John Muir/Mt. Diablo Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers - Aurora
    • Colorado Springs, Colorado, United States, 80909
      • Rocky Mountain Cancer Centers - Colorado Springs
    • Fort Collins, Colorado, United States, 80528
      • Poudre Valley Radiation Oncology
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8028
      • Yale Cancer Center
  • Delaware
    • Newark, Delaware, United States, 19713
      • CCOP - Christiana Care Health Services
  • District of Columbia
    • Washington, D.C., District of Columbia, United States, 20010
      • Washington Cancer Institute at Washington Hospital Center
  • Florida
    • Gainesville, Florida, United States, 32610-0232
      • University of Florida Shands Cancer Center
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute - Jacksonville
    • Jacksonville, Florida, United States, 32207
      • Integrated Community Oncology Network at Southside Cancer Center
    • Jacksonville, Florida, United States, 32258
      • Baptist Medical Center South
    • Jacksonville Beach, Florida, United States, 32250
      • Integrated Community Oncology Network
    • Orange Park, Florida, United States, 32073
      • Integrated Community Oncology Network - Orange Park
    • Orlando, Florida, United States, 32806
      • Florida Institute of Research, Medicine and Surgery Cancer Center
    • Palatka, Florida, United States, 32177
      • Florida Cancer Center - Palatka
    • Saint Augustine, Florida, United States, 32086
      • Flagler Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center
    • Decatur, Georgia, United States, 30033
      • Veterans Affairs Medical Center - Atlanta (Decatur)
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Northwest Community Hospital
    • Chicago, Illinois, United States, 60612-3785
      • John H. Stroger, Jr. Hospital of Cook County
    • Springfield, Illinois, United States, 62702
      • Cancer Institute at St. John's Hospital
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Saint John's Cancer Center at Saint John's Medical Center
    • Bloomington, Indiana, United States, 47403
      • Bloomington Hospital Regional Cancer Institute
    • Fort Wayne, Indiana, United States, 46805
      • Parkview Regional Cancer Center at Parkview Health
    • Fort Wayne, Indiana, United States, 46804
      • Radiation Oncology Associates Southwest
    • Goshen, Indiana, United States, 46526
      • Center for Cancer Care at Goshen General Hospital
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Methodist Cancer Center at Methodist Hospital
    • Indianapolis, Indiana, United States, 46219
      • Central Indiana Cancer Centers - East
    • Indianapolis, Indiana, United States, 46219
      • Community Regional Cancer Care at Community Hospital East
    • Indianapolis, Indiana, United States, 46256
      • Community Regional Cancer Care at Community Hospital North
    • Muncie, Indiana, United States, 47303-3499
      • Cancer Center at Ball Memorial Hospital
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
  • Iowa
    • Iowa City, Iowa, United States, 52242-1002
      • Holden Comprehensive Cancer Center at University of Iowa
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Kansas City Cancer Centers - Southwest
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • Lucille P. Markey Cancer Center at University of Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Suburban Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Hospital Cancer Center
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center at University of Maryland Medical Center
    • Baltimore, Maryland, United States, 21237
      • Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
    • Baltimore, Maryland, United States, 21239
      • Good Samaritan Hospital of Maryland
    • Columbia, Maryland, United States, 21044
      • Central Maryland Oncology Center
    • Glen Burnie, Maryland, United States, 21061
      • Tate Cancer Center at Baltimore Washington Medical Center
    • Towson, Maryland, United States, 21204
      • Cancer Institute at St. Joseph Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Cancer Research Center
  • Michigan
    • Commerce, Michigan, United States, 48382
      • Charach Cancer Center at Huron Valley - Sinai Hospital
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Flint, Michigan, United States, 48532
      • Great Lakes Cancer Institute at McLaren Regional Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Livonia, Michigan, United States, 48154
      • St. Mary Mercy Hospital
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital - Royal Oak Campus
  • Minnesota
    • Albert Lea, Minnesota, United States, 56007
      • Albert Lea Cancer Center at Albert Lea Medical Center
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy and Unity Cancer Center at Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Mankato, Minnesota, United States, 56002
      • Immanuel St. Joseph's
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology, PA - Maplewood
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
    • Robbinsdale, Minnesota, United States, 55422-2900
      • Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Clinic - River Campus
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Regional Cancer Center at Singing River Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64154
      • Kansas City Cancer Centers - North
    • Kansas City, Missouri, United States, 64131
      • Kansas City Cancer Centers - South
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Estabrook Cancer Center
    • Omaha, Nebraska, United States, 68198
      • Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Nevada Cancer Research Foundation
    • Reno, Nevada, United States, 89502
      • Renown Institute for Cancer at Renown Regional Medical Center
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • Payson Center for Cancer Care at Concord Hospital
    • Manchester, New Hampshire, United States, 03103
      • Elliot Regional Cancer Center at Elliot Hospital
  • New Jersey
    • Bricktown, New Jersey, United States, 08724
      • Ocean Medical Center at Meridian Health
    • Camden, New Jersey, United States, 08103
      • Cancer Institute of New Jersey at Cooper University Hospital - Camden
    • Elizabeth, New Jersey, United States, 07207
      • Trinitas Comprehensive Cancer Center at Trinitas Hospital
    • Jamesburg, New Jersey, United States, 08831
      • Princeton Radiation Oncology Center
    • New Brunswick, New Jersey, United States, 08901
      • Saint Peter's University Hospital
    • Princeton, New Jersey, United States, 08540-3298
      • University Medical Center at Princeton
    • Toms River, New Jersey, United States, 08755
      • J. Phillip Citta Regional Cancer Center at Community Medical Center
    • Voorhees, New Jersey, United States, 08043
      • Cancer Institute of New Jersey at Cooper - Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87102
      • Lovelace Medical Center - Downtown
    • Albuquerque, New Mexico, United States, 87109
      • Radiation Oncology Associates, PA
  • New York
    • Albany, New York, United States, 12208
      • Veterans Affairs Medical Center - Albany
    • Albany, New York, United States, 12206
      • New York Oncology Hematology, PC at Albany Regional Cancer Care
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Canandaigua, New York, United States, 14424
      • Sands Cancer Center
    • Manhasset, New York, United States, 11030
      • CCOP - North Shore University Hospital
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Rochester, New York, United States, 14620
      • Highland Hospital of Rochester
    • Rochester, New York, United States, 14621
      • Lipson Cancer and Blood Center at Rochester General Hospital
    • Rochester, New York, United States, 14626
      • University Radiation Oncology at Parkridge Hospital
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospitals - Memorial Campus
    • Wilmington, North Carolina, United States, 28401
      • New Hanover Radiation Oncology, PA
  • North Dakota
    • Minot, North Dakota, United States, 58701
      • Trinity Cancercare Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Akron, Ohio, United States, 44309-2090
      • Summa Center for Cancer Care at Akron City Hospital
    • Barberton, Ohio, United States, 44203
      • Barberton Citizens Hospital
    • Cincinnati, Ohio, United States, 45267
      • Charles M. Barrett Cancer Center at University Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center at Fairview Hospital
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center
    • Maumee, Ohio, United States, 43537-1839
      • Northwest Ohio Oncology Center
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Cancer Center at Hillcrest Hospital
    • Oregon, Ohio, United States, 43616
      • St. Charles Mercy Hospital
    • Salem, Ohio, United States, 44460
      • Cancer Care Center, Incorporated
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care, Incorporated
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital Cancer Center
    • Toledo, Ohio, United States, 43614
      • Medical University of Ohio Cancer Center
    • Toledo, Ohio, United States, 43617
      • CCOP - Toledo Community Hospital
    • Toledo, Ohio, United States, 43623
      • St. Anne Mercy Hospital
    • West Chester, Ohio, United States, 45069
      • Precision Radiotherapy at University Pointe
    • Wooster, Ohio, United States, 44691
      • Cancer Treatment Center
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic - Wooster
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Cancer Institute
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Center - Eugene
    • Grants Pass, Oregon, United States, 97527
      • Three Rivers Community Hospital
    • Medford, Oregon, United States, 97504
      • Dubs Cancer Center at Rogue Valley Medical Center
    • Medford, Oregon, United States, 97504
      • Providence Cancer Center at PMCC
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Rosenfeld Cancer Center at Abington Memorial Hospital
    • Beaver, Pennsylvania, United States, 15009
      • UPMC Cancer Center at Beaver Medical Center
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's Cancer Network at St. Luke's Hospital
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Clairton, Pennsylvania, United States, 15025
      • UPMC Cancer Center at Jefferson Regional Medical Center
    • Clarion, Pennsylvania, United States, 16214
      • Cancer Center at Clarion Hospital
    • Danville, Pennsylvania, United States, 17822-0001
      • Geisinger Cancer Institute at Geisinger Health
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Regional Cancer Center at Delaware County Memorial Hospital
    • Dunmore, Pennsylvania, United States, 18512
      • Northeast Radiation Oncology Center
    • Gettysburg, Pennsylvania, United States, 17325
      • Adams Cancer Center
    • Greensburg, Pennsylvania, United States, 15601
      • UPMC Cancer Center - Arnold Palmer Pavilion
    • Hanover, Pennsylvania, United States, 17331
      • Cherry Tree Cancer Center
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Cancer Institute at Milton S. Hershey Medical Center
    • Johnstown, Pennsylvania, United States, 15901
      • UPMC Cancer Center at the John P. Murtha Pavilion
    • McKeesport, Pennsylvania, United States, 15132
      • UPMC Cancer Center at UPMC McKeesport
    • Moon, Pennsylvania, United States, 15108
      • UPMC - Moon
    • Natrona Heights, Pennsylvania, United States, 15065
      • UPMC Cancer Center - Natrona Heights
    • New Castle, Pennsylvania, United States, 16105
      • Jameson Memorial Hospital - North Campus
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center - Philadelphia
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213-2582
      • UPMC - Shadyside
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Cancer Center at Magee-Womens Hospital
    • Pittsburgh, Pennsylvania, United States, 15215
      • UPMC Cancer Center at UPMC St. Margaret
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC Cancer Center at UPMC Passavant
    • Pittsburgh, Pennsylvania, United States, 15243
      • UPMC Cancer Center - Upper St. Clair
    • Seneca, Pennsylvania, United States, 16346
      • UPMC Cancer Center at UPMC Northwest
    • Uniontown, Pennsylvania, United States, 15401
      • UPMC Cancer Center - Uniontown
    • Washington, Pennsylvania, United States, 15301
      • Washington Hospital Cancer Center
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Cancer Center at Lankenau Hospital
    • York, Pennsylvania, United States, 17405
      • York Cancer Center at Apple Hill Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
  • Texas
    • Arlington, Texas, United States, 76014
      • Texas Oncology, PA at Texas Cancer Center - Arlington South
    • Bedford, Texas, United States, 76022
      • Texas Oncology, PA at Harris Center HEB
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • Dallas, Texas, United States, 75390
      • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
    • Dallas, Texas, United States, 75237
      • Texas Oncology, PA at Texas Cancer Center Dallas Southwest
    • Denton, Texas, United States, 76210
      • Texas Oncology, PA at Texas Cancer Center - Denton South
    • Fort Worth, Texas, United States, 76104
      • Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital
    • Longview, Texas, United States, 75601
      • Longview Cancer Center
    • Odessa, Texas, United States, 79761
      • West Texas Cancer Center
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas - Northeast
    • Sherman, Texas, United States, 75090
      • Texas Oncology, PA at Texas Cancer Center - Sherman
    • Sugar Land, Texas, United States, 77479
      • Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land
    • Tyler, Texas, United States, 75702
      • Tyler Cancer Center
  • Utah
    • Murray, Utah, United States, 84157
      • Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute at University of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care - University Health Center Campus
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Norfolk, Virginia, United States, 23507
      • Sentara Cancer Institute at Sentara Norfolk General Hospital
  • Washington
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
  • West Virginia
    • Wheeling, West Virginia, United States, 26003
      • Schiffler Cancer Center at Wheeling Hospital
  • Wisconsin
    • Appleton, Wisconsin, United States, 54911
      • Theda Care Cancer Institute
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital Regional Cancer Center
    • La Crosse, Wisconsin, United States, 54601
      • Franciscan Skemp Healthcare - La Crosse Campus
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Cancer Care Center at Bay Area Medical Center
    • Menomonee Falls, Wisconsin, United States, 53051
      • Community Memorial Hospital Cancer Care Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center
    • Milwaukee, Wisconsin, United States, 53215
      • Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
    • Racine, Wisconsin, United States, 53405
      • All Saints Cancer Center at Wheaton Franciscan Healthcare
    • Wausau, Wisconsin, United States, 54401
      • University of Wisconcin Cancer Center at Aspirus Wausau Hospital
    • West Allis, Wisconsin, United States, 53227
      • West Allis Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed diagnosis of a solid tumor malignancy within the past 5 years

  • If the original histologic proof of malignancy is > 5 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic metastasis or brain metastasis)

• Brain metastases must be visible on contrast-enhanced MRI or a contrast enhanced CT scan (for patients unable to undergo MRI within the past 28 days)

  • Patients unable to undergo MRI imaging because of non-compatible devices are eligible, provided the contrast-enhanced CT scans are obtained and are of sufficient quality
  • Patients who had undergone radiosurgery or surgical resection and are planning adjuvant whole-brain radiotherapy do not have to have visible disease but do need a baseline MRI
• Must have stable systemic disease (i.e. no evidence of systemic disease progression within the past 3 months)
• Patients with brain metastases at initial presentation are eligible and do not need to demonstrate 3 months of stable scans

PATIENT CHARACTERISTICS:

Inclusion

• Karnofsky performance status 70-100%
• Serum creatinine ≤ 3 mg/dL and creatinine clearance ≥ 30 mL/min
• Total bilirubin ≤ 2.5 mg/dL
• Blood urea nitrogen (BUN) < 20 mg/dL
• Mini-mental status exam score ≥ 18
• Negative serum pregnancy test
• Fertile patients must practice adequate contraception

Exclusion

• 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 respiratory illness requiring hospitalization or precluding study therapy at the time of registration
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• Pregnant or lactating women
• Prior allergic reaction to memantine hydrochloride
• Current alcohol or drug abuse
• Intractable seizures while on adequate anticonvulsant therapy (i.e., more than one seizure per month for the past 2 months)

PRIOR CONCURRENT THERAPY:

Inclusion

• At least 14 days but no more than 56 days since prior therapy for brain metastasis, including radiosurgery and surgical resection
• No systemic chemotherapy for 14 days prior, during, or for 14 days after completion of whole-brain radiotherapy (WBRT)

Exclusion

• Prior cranial radiotherapy

  • Patients may have received up to 3 prior WBRT treatments and still be registered and randomized on the protocol provided WBRT parameters meet protocol requirements
• Chronic short-acting benzodiazepine use

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WBRT+Memantine; Whole brain radiation therapy (WBRT) and memantine	Drug: Memantine; Patients began taking memantine(by mouth) while receiving radiation therapy. Patients continued taking memantine for 24 weeks or until doctor thinks it is in their best interest to stop. They started with 5 mg once a day. After a week dose increased to 5 mg twice a day. At week 3, dose increased to 10 mg in the morning and 5 mg in the evening. Weeks 4-24, dose was 10 mg twice a day.; Radiation: Whole brain radiation therapy; Whole brain radiation therapy (WBRT) once a day (2.5Gy), five days a week (Monday to Friday) for three weeks, for total fifteen treatments and 37.5 Gy
Active Comparator: WBRT+Placebo; Whole brain radiation therapy (WBRT) and placebo	Radiation: Whole brain radiation therapy; Whole brain radiation therapy (WBRT) once a day (2.5Gy), five days a week (Monday to Friday) for three weeks, for total fifteen treatments and 37.5 Gy; Other: Placebo; Patients began taking placebo(by mouth) while receiving radiation therapy. Patients continued taking placebo for 24 weeks or until doctor thinks it is in their best interest to stop. They started with 5 mg once a day. After a week dose increased to 5 mg twice a day. At week 3, dose increased to 10 mg in the morning and 5 mg in the evening. Weeks 4-24, dose was 10 mg twice a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Hopkins Verbal Learning Test - Revised for Delayed Recall (HVLT-R-delayed Recall) at 24 Weeks	The HVLT-R consists of 3 parts. Free call has a range of 0 to 36, delayed recall has a range from 0 to 12, and delayed recognition has a range of -12 to 12. Higher scores indicating better function in all 3 parts. Standardized scores are used by calculating an average standardized z score for each part of the HVLT-R. Change is calculated by subtracting baseline value from 24-week value. Imputation methods were used to determine values for all alive patients missing the 24 week assessment. This tool is being used to measure cognitive function, specifically memory.	Baseline and 24 weeks from the start of drug treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Hopkins Verbal Learning Test - Revised for Delayed Recall (HVLT-R-delayed Recall) at 8, 16, and 52 Weeks	The HVLT-R consists of 3 parts. Free call has a range of 0 to 36, delayed recall has a range from 0 to 12, and delayed recognition has a range of -12 to 12. Higher scores indicating better function in all 3 parts. Standardized scores are used by calculating an average standardized z score for each part of the HVLT-R. Change is calculated by subtracting baseline value from the respective later time point value. Imputation methods were used to determine values for all alive patients missing the post-baseline assessments. This tool is being used to measure cognitive function, specifically memory.	Baseline, 8, 16, and 52 weeks from the start of drug treatment
Median Time to Neurocognitive Failure	Neurocognitive failure is defined as the first cognitive failure on any of the neurocognitive tests: the HVLT-R for immediate recall, delayed recognition, and delayed recall; the Controlled Oral Word Association Test (COWAT); the Trail-Making Test (TMT) Parts A and B. Cognitive failure for each test is defined as a post-treatment score that meets one of the following criteria: follow-up score is at least 2 standard deviations worse than the patient's personal baseline score or the patient's raw score change is greater than the reliable change index. The cumulative incidence approach was used to estimate the median time to neurocognitive failure to account for the competing risks of disease progression and death.	Baseline to 12 months from the start of drug treatment
Change in Functional Assessment of Cancer Therapy With Brain Subscale (FACT-Br) at 24 Weeks	The FACT-Br is a 50-question self-report questionnaire contains the following domains (scales): Physical well-being (7 questions), social/family well-being (7 questions), emotional well-being (6 questions), functional well-being (7 questions) and brain cancer subscale which contains concerns relevant to patients with brain tumors (23 questions). Each question has a value 0-4. For some questions a higher indicates better outcome and others are the opposite. The former are summed as is, the latter are reversed in value before adding, such that each domain ranges from 0 to 4 times the number of questions in the domain, with 0 indicating worst and the highest possible value indicating best outcome. The FACT-Br total is obtained by adding all domains together if the overall question response rate is greater than 80%. Total scores on the FACT-Br range from 0 to 184 with lower scores indicating declining quality of life. Change is calculated as baseline score subtracted from 24-week score.	Baseline and 24 weeks from start of treatment
Median Progression-free Survival Time	Disease progression is defined as the first of the following events: an increase of at least 50% for lesions less than or equal to 1cm, an increase of least 25% for lesions greater than 1cm, appearance of any new brain metastases. Failure for progression-free survival is disease progression or death. Median progression-free survival was estimated using the Kaplan-Meier method.	From randomization to date of progression, death or last follow-up. Analysis occurs at the same time as the primary outcome. Patients are followed until death and all follow-up collected at time of analysis is used.
Overall Survival	Failure for overall survival is death from any cause. Median survival was estimated using the Kaplan-Meier method.	From randomization to date of death or last follow-up. Analysis occurs at the same time as the primary outcome. Patients are followed until death and all follow-up collected at time of analysis is used.

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology
• Investigators: Principal Investigator: Paul D. Brown, MD, Mayo Clinic; Study Chair: Christina A. Meyers, PhD, M.D. Anderson Cancer Center; Study Chair: Sherry Fox, RN, PhD, Bon Secours Cancer Institute at St. Mary's Hospital; Study Chair: Deepak Khuntia, MD, University of Wisconsin, Madison

Publications and helpful links

General Publications

• Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, Choucair A, Fox S, Suh JH, Roberge D, Kavadi V, Bentzen SM, Mehta MP, Watkins-Bruner D; Radiation Therapy Oncology Group (RTOG). Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013 Oct;15(10):1429-37. doi: 10.1093/neuonc/not114. Epub 2013 Aug 16.

Helpful Links

• Manuscript for primary analysis results

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: December 1, 2007
• First Submitted That Met QC Criteria: December 1, 2007
• First Posted (Estimate): December 4, 2007

Study Record Updates

• Last Update Posted (Actual): August 21, 2017
• Last Update Submitted That Met QC Criteria: July 21, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific; neurotoxicity; tumors metastatic to brain; cognitive/functional effects
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Poisoning; Neurotoxicity Syndromes; 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: RTOG-0614; CDR0000577872; NCI-2009-00735 (Registry Identifier: CTRP (Clinical Trial Reporting Program))