Back to resultsMemantine Hydrochloride and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Reducing Neurocognitive Decline in Patients With Brain Metastases
Primary Purpose
Cognitive Impairment, Metastatic Malignant Neoplasm in the Brain, Solid Neoplasm
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Whole brain radiation therapy with hippocampal avoidance
Memantine
Whole brain radiation therapy
Sponsored by
About this trial
This is an interventional supportive care trial for Cognitive Impairment
Eligibility Criteria
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
Sites / Locations
- Lewis and Faye Manderson Cancer Center
- Banner MD Anderson Cancer Center
- Banner University Medical Center - Tucson
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Mercy San Juan Medical Center
- City of Hope Comprehensive Cancer Center
- UC San Diego Moores Cancer Center
- Kaiser Permanente Los Angeles Medical Center
- Los Angeles County-USC Medical Center
- USC / Norris Comprehensive Cancer Center
- Kaiser Permanente Oakland-Broadway
- Stanford Cancer Institute Palo Alto
- Kaiser Permanente-Rancho Cordova Cancer Center
- Rohnert Park Cancer Center
- Sutter Cancer Centers Radiation Oncology Services-Roseville
- The Permanente Medical Group-Roseville Radiation Oncology
- Mercy Cancer Center - Sacramento
- Sutter Medical Center Sacramento
- University of California San Diego
- California Pacific Medical Center-Pacific Campus
- Stanford Cancer Center South Bay
- Kaiser Permanente Medical Center - Santa Clara
- Kaiser Permanente Cancer Treatment Center
- Sutter Solano Medical Center/Cancer Center
- Rocky Mountain Cancer Centers-Boulder
- Penrose-Saint Francis Healthcare
- UCHealth Memorial Hospital Central
- Swedish Medical Center
- Saint Vincent's Medical Center
- Helen F Graham Cancer Center
- Christiana Care Health System-Christiana Hospital
- Boca Raton Regional Hospital
- UM Sylvester Comprehensive Cancer Center at Coral Gables
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- UF Cancer Center at Orlando Health
- Cleveland Clinic-Weston
- Grady Health System
- Emory University Hospital Midtown
- Piedmont Hospital
- Emory University Hospital/Winship Cancer Institute
- Emory Saint Joseph's Hospital
- Memorial Health University Medical Center
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Saint Alphonsus Cancer Care Center-Boise
- Saint Luke's Mountain States Tumor Institute
- Saint Luke's Mountain States Tumor Institute - Meridian
- Saint Luke's Mountain States Tumor Institute - Nampa
- Saint Luke's Mountain States Tumor Institute-Twin Falls
- SIH Cancer Institute
- Northwestern University
- John H Stroger Jr Hospital of Cook County
- University of Chicago Comprehensive Cancer Center
- Decatur Memorial Hospital
- Crossroads Cancer Center
- Northwestern Medicine Cancer Center Delnor
- Edward Hines Jr VA Hospital
- Condell Memorial Hospital
- Loyola University Medical Center
- Methodist Medical Center of Illinois
- OSF Saint Francis Medical Center
- Memorial Medical Center
- Carle Cancer Center
- Northwestern Medicine Cancer Center Warrenville
- Parkview Hospital Randallia
- Community Cancer Center East
- Community Cancer Center South
- Community Cancer Center North
- Saint Luke's Hospital
- University of Kansas Cancer Center
- Lawrence Memorial Hospital
- University of Kansas Cancer Center-Overland Park
- Ascension Via Christi Hospitals Wichita
- Wesley Medical Center
- University of Kentucky/Markey Cancer Center
- Tulane University Health Sciences Center
- University of Maryland/Greenebaum Cancer Center
- MedStar Union Memorial Hospital
- UM Upper Chesapeake Medical Center
- Central Maryland Radiation Oncology in Howard County
- UM Baltimore Washington Medical Center/Tate Cancer Center
- UM Saint Joseph Medical Center
- Tufts Medical Center
- Lahey Hospital and Medical Center
- Lowell General Hospital
- Saint Joseph Mercy Hospital
- McLaren Cancer Institute-Bay City
- Henry Ford Cancer Institute-Downriver
- Saint Joseph Mercy Chelsea
- 21st Century Oncology MHP - Clarkston
- McLaren Cancer Institute-Clarkston
- Henry Ford Macomb Hospital-Clinton Township
- Wayne State University/Karmanos Cancer Institute
- Henry Ford Hospital
- 21st Century Oncology MHP - Farmington
- Genesys Hurley Cancer Institute
- McLaren Cancer Institute-Flint
- Spectrum Health at Butterworth Campus
- West Michigan Cancer Center
- McLaren Cancer Institute-Lapeer Region
- Saint Mary Mercy Hospital
- McLaren Cancer Institute-Macomb
- McLaren Cancer Institute-Central Michigan
- Mercy Health Mercy Campus
- McLaren Cancer Institute-Owosso
- McLaren Cancer Institute-Northern Michigan
- Saint Joseph Mercy Oakland
- McLaren-Port Huron
- Lakeland Medical Center Saint Joseph
- 21st Century Oncology MHP - Troy
- Henry Ford West Bloomfield Hospital
- Mayo Clinic Health System in Albert Lea
- Unity Hospital
- Mayo Clinic Health Systems-Mankato
- Abbott-Northwestern Hospital
- Mayo Clinic Radiation Therapy-Northfield
- Mayo Clinic
- Park Nicollet Clinic - Saint Louis Park
- Saint Francis Medical Center
- Siteman Cancer Center at West County Hospital
- North Kansas City Hospital
- Washington University School of Medicine
- Siteman Cancer Center-South County
- Missouri Baptist Medical Center
- Mercy Hospital Saint Louis
- Siteman Cancer Center at Saint Peters Hospital
- CoxHealth South Hospital
- Billings Clinic Cancer Center
- Benefis Healthcare- Sletten Cancer Institute
- Community Medical Hospital
- University of Nebraska Medical Center
- Renown Regional Medical Center
- Wentworth-Douglass Hospital
- Dartmouth Hitchcock Medical Center
- Montefiore Medical Center - Moses Campus
- New York-Presbyterian/Brooklyn Methodist Hospital
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- University of Rochester
- UNC Lineberger Comprehensive Cancer Center
- NHRMC Radiation Oncology - 16th Street
- Sanford Bismarck Medical Center
- Sanford Roger Maris Cancer Center
- Summa Akron City Hospital/Cooper Cancer Center
- Cleveland Clinic Akron General
- Case Western Reserve University
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Cleveland Clinic Cancer Center Independence
- UH Seidman Cancer Center at Southwest General Hospital
- University Hospitals Parma Medical Center
- Cleveland Clinic Cancer Center Strongsville
- UHHS-Westlake Medical Center
- University of Oklahoma Health Sciences Center
- Legacy Mount Hood Medical Center
- Legacy Good Samaritan Hospital and Medical Center
- Abington Memorial Hospital
- Crozer-Keystone Regional Cancer Center at Broomall
- Bryn Mawr Hospital
- Christiana Care Health System-Concord Health Center
- Geisinger Medical Center
- Northeast Radiation Oncology Center
- Crozer Regional Cancer Center at Brinton Lake
- Riddle Memorial Hospital
- Thomas Jefferson University Hospital
- Fox Chase Cancer Center
- Aria Health-Torresdale Campus
- Temple University Hospital
- Reading Hospital
- Geisinger Wyoming Valley/Henry Cancer Center
- Lankenau Medical Center
- Greenville Health System Cancer Institute-Faris
- Greenville Health System Cancer Institute-Eastside
- Self Regional Healthcare
- The Radiation Oncology Center-Hilton Head/Bluffton
- Greenville Health System Cancer Institute-Spartanburg
- Sanford USD Medical Center - Sioux Falls
- Vanderbilt University/Ingram Cancer Center
- University of Texas Medical Branch
- M D Anderson Cancer Center
- UTMB Cancer Center at Victory Lakes
- Ogden Regional Medical Center
- Huntsman Cancer Institute/University of Utah
- Norris Cotton Cancer Center-North
- Virginia Commonwealth University/Massey Cancer Center
- Virginia Mason Medical Center
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
- West Virginia University Healthcare
- Wheeling Hospital/Schiffler Cancer Center
- Langlade Hospital and Cancer Center
- Mayo Clinic Health System-Eau Claire Clinic
- Aurora Cancer Care-Grafton
- Aurora BayCare Medical Center
- UW Cancer Center Johnson Creek
- Aurora Cancer Care-Kenosha South
- Gundersen Lutheran Medical Center
- Mayo Clinic Health System-Franciscan Healthcare
- University of Wisconsin Hospital and Clinics
- Community Memorial Hospital
- Ascension Columbia Saint Mary's Water Tower Medical Commons
- Aurora Saint Luke's Medical Center
- Medical College of Wisconsin
- Aurora Sinai Medical Center
- Zablocki Veterans Administration Medical Center
- Vince Lombardi Cancer Clinic - Oshkosh
- Marshfield Clinic Stevens Point Center
- Aurora Medical Center in Summit
- Vince Lombardi Cancer Clinic-Two Rivers
- Aspirus Regional Cancer Center
- Aurora West Allis Medical Center
- Diagnostic and Treatment Center
- Aspirus UW Cancer Center
- CHUM - Hopital Notre-Dame
- McGill University Department of Oncology
- CHUM - Centre Hospitalier de l'Universite de Montreal
- The Research Institute of the McGill University Health Centre (MUHC)
- CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
- Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
- Allan Blair Cancer Centre
- Saskatoon Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
WBRT + Memantine
HA-WBRT/IMRT+ Memantine
Arm Description
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) using intensity modulated radiation therapy (IMRT) and memantine
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT02360215
First Posted
February 5, 2015
Last Updated
May 12, 2021
Sponsor
NRG Oncology
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT02360215
Brief Title
Memantine Hydrochloride and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Reducing Neurocognitive Decline in Patients With Brain Metastases
Official Title
A Randomized Phase III Trial of Memantine and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Patients With Brain Metastases
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
July 2015 (Actual)
Primary Completion Date
April 30, 2018 (Actual)
Study Completion Date
August 26, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NRG Oncology
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This randomized phase III trial compares memantine hydrochloride and whole-brain radiotherapy with or without hippocampal avoidance in reducing neurocognitive decline in patients with cancer that has spread from the primary site (place where it started) to the brain. Whole brain radiotherapy (WBRT) is the most common treatment for brain metastasis. Unfortunately, the majority of patients with brain metastases experience cognitive (such as learning and memory) deterioration after WBRT. Memantine hydrochloride may enhance cognitive function by binding to and inhibiting channels of receptors located in the central nervous system. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Using radiation techniques, such as intensity modulated radiotherapy to avoid the hippocampal region during WBRT, may reduce the radiation dose to the hippocampus and help limit the radiation-induced cognitive decline. It is not yet known whether giving memantine hydrochloride and WBRT with or without hippocampal avoidance works better in reducing neurocognitive decline in patients with brain metastases.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cognitive Impairment, Metastatic Malignant Neoplasm in the Brain, Solid Neoplasm
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
518 (Actual)
8. Arms, Groups, and Interventions
Arm Title
WBRT + Memantine
Arm Type
Experimental
Arm Description
Whole brain radiation therapy (WBRT) and memantine
Arm Title
HA-WBRT/IMRT+ Memantine
Arm Type
Experimental
Arm Description
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) using intensity modulated radiation therapy (IMRT) and memantine
Intervention Type
Radiation
Intervention Name(s)
Whole brain radiation therapy with hippocampal avoidance
Other Intervention Name(s)
IMRT, Intensity Modulated RT, INTENSITY-MODULATED RADIATION THERAPY, Intensity-Modulated Radiotherapy, Whole-brain radiation therapy, WBRT, whole-brain radiotherapy, HA-WBRT
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Memantine
Other Intervention Name(s)
Ebixia, Memantine Hydrochloride, Namenda
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Whole brain radiation therapy
Other Intervention Name(s)
WBRT, whole-brain radiation therapy, whole-brain radiotherapy
Intervention Description
Whole brain radiation therapy (WBRT) 30 Gy in 10 fractions once per day, 5 days per week for approximately 2 weeks
Primary Outcome Measure Information:
Title
Time to Neurocognitive Failure
Description
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.
Time Frame
From randomization to last follow-up. Maximum follow-up was 15.6 months.
Secondary Outcome Measure Information:
Title
Change From Baseline in the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall Score (Neurocognitive Decline)
Description
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.
Time Frame
Baseline, 2, 4, 6, and 12 months
Title
Change From Baseline in the Hopkins Verbal Learning Test -Revised (HVLT-R) Delayed Recall Score (Neurocognitive Decline)
Description
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.
Time Frame
Baseline, 2, 4, 6, and 12 months
Title
Change From Baseline in the Hopkins Verbal Learning Test -Revised (HVLT-R) Delayed Recognition (Neurocognitive Decline)
Description
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.
Time Frame
Baseline, 2, 4, 6, and 12 months
Title
Change From Baseline in the Trail Making Test (TMT) Part A (Neurocognitive Decline)
Description
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.
Time Frame
Baseline, 2, 4, 6, and 12 months
Title
Change From Baseline in the Trail Making Test (TMT) Part B (Neurocognitive Decline)
Description
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.
Time Frame
Baseline, 2, 4, 6, and 12 months
Title
Change From Baseline in the Controlled Oral Word Association (COWA) Test (Neurocognitive Decline)
Description
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.
Time Frame
Baseline, 2, 4, 6, and 12 months
Title
Change From Baseline in the Clinical Trial Battery Composite (CTB COMP) Score [Neurocognitive Decline]
Description
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.
Time Frame
Baseline, 2, 4, 6, and 12 months
Title
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score
Description
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.
Time Frame
Baseline, 2, 4, 6, and 12 months
Title
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Interference Score
Description
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.
Time Frame
Baseline, 2, 4, 6, and 12 months
Title
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Factor Score
Description
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.
Time Frame
Baseline, 2, 4, 6, and 12 months
Title
Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Neurologic Factor Score
Description
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.
Time Frame
Baseline, 2, 4, 6, and 12 months
Title
Change in EQ-5D-5L Index Score at 2 Months
Description
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.
Time Frame
Baseline and 2 months
Title
Change in EQ-5D-5L Index Score at 4 Months
Description
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.
Time Frame
Baseline and 4 months
Title
Change in EQ-5D-5L Index Score at 6 Months
Description
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.
Time Frame
Baseline and 6 months
Title
Change in EQ-5D-5L Index Score at 12 Months
Description
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.
Time Frame
Baseline and 12 months
Title
Change in EQ-5D-5L VAS Score at 2 Months
Description
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.
Time Frame
Baseline and 2 months
Title
Change in EQ-5D-5L VAS Score at 4 Months
Description
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.
Time Frame
Baseline and 4 months
Title
Change in EQ-5D-5L VAS Score at 6 Months
Description
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.
Time Frame
Baseline and 6 months
Title
Change in EQ-5D-5L VAS Score at 12 Months
Description
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.
Time Frame
Baseline and 12 months
Title
Intracranial Progression-Free Survival
Description
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.
Time Frame
From randomization to last follow-up. Analysis was planned to occur after 233 events were reported. Maximum follow-up was 15.6 months.
Title
Overall Survival
Description
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.
Time Frame
From randomization to last follow-up. Maximum follow-up was 15.6 months.
Title
Number of Patients With a Grade 3+ Adverse Event (AE) Regardless of Relationship to Treatment
Description
. 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.
Time Frame
From randomization to last follow-up. Analysis was planned to occur after 233 events were reported. Maximum follow-up was 15.6 months.
Other Pre-specified Outcome Measures:
Title
Anxiety/Depression Measured Using the EQ-5D-5L
Description
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.
Time Frame
Up to 12 months
Title
Effect of Radiation Therapy Oncology Group (RTOG) RPA and the Diagnosis-specific Graded Prognostic Assessment (DSGPA) on Neurocognitive Function
Description
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.
Time Frame
Up to 12 months
Title
Effect of White Matter Injury and Hippocampal Volume on Neurocognitive Function
Description
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.
Time Frame
Up to 12 months
Title
MDASI-BT Mood Variables
Description
The relationship between EQ-5D-5L and MDASI-BT mood variables and neurocognitive function will be assessed.
Time Frame
Up to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Brown
Organizational Affiliation
NRG Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lewis and Faye Manderson Cancer Center
City
Tuscaloosa
State/Province
Alabama
ZIP/Postal Code
35401
Country
United States
Facility Name
Banner MD Anderson Cancer Center
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
Banner University Medical Center - Tucson
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
Providence Saint Joseph Medical Center/Disney Family Cancer Center
City
Burbank
State/Province
California
ZIP/Postal Code
91505
Country
United States
Facility Name
Mercy San Juan Medical Center
City
Carmichael
State/Province
California
ZIP/Postal Code
95608
Country
United States
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
UC San Diego Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Kaiser Permanente Los Angeles Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Los Angeles County-USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
USC / Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Kaiser Permanente Oakland-Broadway
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
Facility Name
Stanford Cancer Institute Palo Alto
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Kaiser Permanente-Rancho Cordova Cancer Center
City
Rancho Cordova
State/Province
California
ZIP/Postal Code
95670
Country
United States
Facility Name
Rohnert Park Cancer Center
City
Rohnert Park
State/Province
California
ZIP/Postal Code
94928
Country
United States
Facility Name
Sutter Cancer Centers Radiation Oncology Services-Roseville
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Facility Name
The Permanente Medical Group-Roseville Radiation Oncology
City
Roseville
State/Province
California
ZIP/Postal Code
95678
Country
United States
Facility Name
Mercy Cancer Center - Sacramento
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
Sutter Medical Center Sacramento
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
University of California San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
California Pacific Medical Center-Pacific Campus
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Stanford Cancer Center South Bay
City
San Jose
State/Province
California
ZIP/Postal Code
95124
Country
United States
Facility Name
Kaiser Permanente Medical Center - Santa Clara
City
Santa Clara
State/Province
California
ZIP/Postal Code
95051
Country
United States
Facility Name
Kaiser Permanente Cancer Treatment Center
City
South San Francisco
State/Province
California
ZIP/Postal Code
94080
Country
United States
Facility Name
Sutter Solano Medical Center/Cancer Center
City
Vallejo
State/Province
California
ZIP/Postal Code
94589
Country
United States
Facility Name
Rocky Mountain Cancer Centers-Boulder
City
Boulder
State/Province
Colorado
ZIP/Postal Code
80304
Country
United States
Facility Name
Penrose-Saint Francis Healthcare
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
UCHealth Memorial Hospital Central
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80909
Country
United States
Facility Name
Swedish Medical Center
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
Saint Vincent's Medical Center
City
Bridgeport
State/Province
Connecticut
ZIP/Postal Code
06606
Country
United States
Facility Name
Helen F Graham Cancer Center
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
Christiana Care Health System-Christiana Hospital
City
Newark
State/Province
Delaware
ZIP/Postal Code
19718
Country
United States
Facility Name
Boca Raton Regional Hospital
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
UM Sylvester Comprehensive Cancer Center at Coral Gables
City
Coral Gables
State/Province
Florida
ZIP/Postal Code
33146
Country
United States
Facility Name
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
City
Deerfield Beach
State/Province
Florida
ZIP/Postal Code
33442
Country
United States
Facility Name
University of Miami Miller School of Medicine-Sylvester Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
UF Cancer Center at Orlando Health
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Cleveland Clinic-Weston
City
Weston
State/Province
Florida
ZIP/Postal Code
33331
Country
United States
Facility Name
Grady Health System
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Emory University Hospital Midtown
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Piedmont Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Emory University Hospital/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Emory Saint Joseph's Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Memorial Health University Medical Center
City
Savannah
State/Province
Georgia
ZIP/Postal Code
31404
Country
United States
Facility Name
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
City
Savannah
State/Province
Georgia
ZIP/Postal Code
31405
Country
United States
Facility Name
Saint Alphonsus Cancer Care Center-Boise
City
Boise
State/Province
Idaho
ZIP/Postal Code
83706
Country
United States
Facility Name
Saint Luke's Mountain States Tumor Institute
City
Boise
State/Province
Idaho
ZIP/Postal Code
83712
Country
United States
Facility Name
Saint Luke's Mountain States Tumor Institute - Meridian
City
Meridian
State/Province
Idaho
ZIP/Postal Code
83642
Country
United States
Facility Name
Saint Luke's Mountain States Tumor Institute - Nampa
City
Nampa
State/Province
Idaho
ZIP/Postal Code
83686
Country
United States
Facility Name
Saint Luke's Mountain States Tumor Institute-Twin Falls
City
Twin Falls
State/Province
Idaho
ZIP/Postal Code
83301
Country
United States
Facility Name
SIH Cancer Institute
City
Carterville
State/Province
Illinois
ZIP/Postal Code
62918
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
John H Stroger Jr Hospital of Cook County
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Decatur Memorial Hospital
City
Decatur
State/Province
Illinois
ZIP/Postal Code
62526
Country
United States
Facility Name
Crossroads Cancer Center
City
Effingham
State/Province
Illinois
ZIP/Postal Code
62401
Country
United States
Facility Name
Northwestern Medicine Cancer Center Delnor
City
Geneva
State/Province
Illinois
ZIP/Postal Code
60134
Country
United States
Facility Name
Edward Hines Jr VA Hospital
City
Hines
State/Province
Illinois
ZIP/Postal Code
60141
Country
United States
Facility Name
Condell Memorial Hospital
City
Libertyville
State/Province
Illinois
ZIP/Postal Code
60048
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Methodist Medical Center of Illinois
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61636
Country
United States
Facility Name
OSF Saint Francis Medical Center
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61637
Country
United States
Facility Name
Memorial Medical Center
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62781
Country
United States
Facility Name
Carle Cancer Center
City
Urbana
State/Province
Illinois
ZIP/Postal Code
61801
Country
United States
Facility Name
Northwestern Medicine Cancer Center Warrenville
City
Warrenville
State/Province
Illinois
ZIP/Postal Code
60555
Country
United States
Facility Name
Parkview Hospital Randallia
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46805
Country
United States
Facility Name
Community Cancer Center East
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46219
Country
United States
Facility Name
Community Cancer Center South
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46227
Country
United States
Facility Name
Community Cancer Center North
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46256
Country
United States
Facility Name
Saint Luke's Hospital
City
Cedar Rapids
State/Province
Iowa
ZIP/Postal Code
52402
Country
United States
Facility Name
University of Kansas Cancer Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Lawrence Memorial Hospital
City
Lawrence
State/Province
Kansas
ZIP/Postal Code
66044
Country
United States
Facility Name
University of Kansas Cancer Center-Overland Park
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66210
Country
United States
Facility Name
Ascension Via Christi Hospitals Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Wesley Medical Center
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
University of Kentucky/Markey Cancer Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Tulane University Health Sciences Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
University of Maryland/Greenebaum Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
MedStar Union Memorial Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21218
Country
United States
Facility Name
UM Upper Chesapeake Medical Center
City
Bel Air
State/Province
Maryland
ZIP/Postal Code
21014
Country
United States
Facility Name
Central Maryland Radiation Oncology in Howard County
City
Columbia
State/Province
Maryland
ZIP/Postal Code
21044
Country
United States
Facility Name
UM Baltimore Washington Medical Center/Tate Cancer Center
City
Glen Burnie
State/Province
Maryland
ZIP/Postal Code
21061
Country
United States
Facility Name
UM Saint Joseph Medical Center
City
Towson
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Lahey Hospital and Medical Center
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
Lowell General Hospital
City
Lowell
State/Province
Massachusetts
ZIP/Postal Code
01854
Country
United States
Facility Name
Saint Joseph Mercy Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
McLaren Cancer Institute-Bay City
City
Bay City
State/Province
Michigan
ZIP/Postal Code
48706
Country
United States
Facility Name
Henry Ford Cancer Institute-Downriver
City
Brownstown
State/Province
Michigan
ZIP/Postal Code
48183
Country
United States
Facility Name
Saint Joseph Mercy Chelsea
City
Chelsea
State/Province
Michigan
ZIP/Postal Code
48118
Country
United States
Facility Name
21st Century Oncology MHP - Clarkston
City
Clarkston
State/Province
Michigan
ZIP/Postal Code
48346
Country
United States
Facility Name
McLaren Cancer Institute-Clarkston
City
Clarkston
State/Province
Michigan
ZIP/Postal Code
48346
Country
United States
Facility Name
Henry Ford Macomb Hospital-Clinton Township
City
Clinton Township
State/Province
Michigan
ZIP/Postal Code
48038
Country
United States
Facility Name
Wayne State University/Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
21st Century Oncology MHP - Farmington
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Facility Name
Genesys Hurley Cancer Institute
City
Flint
State/Province
Michigan
ZIP/Postal Code
48503
Country
United States
Facility Name
McLaren Cancer Institute-Flint
City
Flint
State/Province
Michigan
ZIP/Postal Code
48532
Country
United States
Facility Name
Spectrum Health at Butterworth Campus
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
West Michigan Cancer Center
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
McLaren Cancer Institute-Lapeer Region
City
Lapeer
State/Province
Michigan
ZIP/Postal Code
48446
Country
United States
Facility Name
Saint Mary Mercy Hospital
City
Livonia
State/Province
Michigan
ZIP/Postal Code
48154
Country
United States
Facility Name
McLaren Cancer Institute-Macomb
City
Mount Clemens
State/Province
Michigan
ZIP/Postal Code
48043
Country
United States
Facility Name
McLaren Cancer Institute-Central Michigan
City
Mount Pleasant
State/Province
Michigan
ZIP/Postal Code
48858
Country
United States
Facility Name
Mercy Health Mercy Campus
City
Muskegon
State/Province
Michigan
ZIP/Postal Code
49444
Country
United States
Facility Name
McLaren Cancer Institute-Owosso
City
Owosso
State/Province
Michigan
ZIP/Postal Code
48867
Country
United States
Facility Name
McLaren Cancer Institute-Northern Michigan
City
Petoskey
State/Province
Michigan
ZIP/Postal Code
49770
Country
United States
Facility Name
Saint Joseph Mercy Oakland
City
Pontiac
State/Province
Michigan
ZIP/Postal Code
48341
Country
United States
Facility Name
McLaren-Port Huron
City
Port Huron
State/Province
Michigan
ZIP/Postal Code
48060
Country
United States
Facility Name
Lakeland Medical Center Saint Joseph
City
Saint Joseph
State/Province
Michigan
ZIP/Postal Code
49085
Country
United States
Facility Name
21st Century Oncology MHP - Troy
City
Troy
State/Province
Michigan
ZIP/Postal Code
48098
Country
United States
Facility Name
Henry Ford West Bloomfield Hospital
City
West Bloomfield
State/Province
Michigan
ZIP/Postal Code
48322
Country
United States
Facility Name
Mayo Clinic Health System in Albert Lea
City
Albert Lea
State/Province
Minnesota
ZIP/Postal Code
56007
Country
United States
Facility Name
Unity Hospital
City
Fridley
State/Province
Minnesota
ZIP/Postal Code
55432
Country
United States
Facility Name
Mayo Clinic Health Systems-Mankato
City
Mankato
State/Province
Minnesota
ZIP/Postal Code
56001
Country
United States
Facility Name
Abbott-Northwestern Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Mayo Clinic Radiation Therapy-Northfield
City
Northfield
State/Province
Minnesota
ZIP/Postal Code
55057
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Park Nicollet Clinic - Saint Louis Park
City
Saint Louis Park
State/Province
Minnesota
ZIP/Postal Code
55416
Country
United States
Facility Name
Saint Francis Medical Center
City
Cape Girardeau
State/Province
Missouri
ZIP/Postal Code
63703
Country
United States
Facility Name
Siteman Cancer Center at West County Hospital
City
Creve Coeur
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
North Kansas City Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64116
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Siteman Cancer Center-South County
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63129
Country
United States
Facility Name
Missouri Baptist Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63131
Country
United States
Facility Name
Mercy Hospital Saint Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Siteman Cancer Center at Saint Peters Hospital
City
Saint Peters
State/Province
Missouri
ZIP/Postal Code
63376
Country
United States
Facility Name
CoxHealth South Hospital
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65807
Country
United States
Facility Name
Billings Clinic Cancer Center
City
Billings
State/Province
Montana
ZIP/Postal Code
59101
Country
United States
Facility Name
Benefis Healthcare- Sletten Cancer Institute
City
Great Falls
State/Province
Montana
ZIP/Postal Code
59405
Country
United States
Facility Name
Community Medical Hospital
City
Missoula
State/Province
Montana
ZIP/Postal Code
59804
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Renown Regional Medical Center
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
Wentworth-Douglass Hospital
City
Dover
State/Province
New Hampshire
ZIP/Postal Code
03820
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Montefiore Medical Center - Moses Campus
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
New York-Presbyterian/Brooklyn Methodist Hospital
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11215
Country
United States
Facility Name
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
UNC Lineberger Comprehensive Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
NHRMC Radiation Oncology - 16th Street
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
Sanford Bismarck Medical Center
City
Bismarck
State/Province
North Dakota
ZIP/Postal Code
58501
Country
United States
Facility Name
Sanford Roger Maris Cancer Center
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58122
Country
United States
Facility Name
Summa Akron City Hospital/Cooper Cancer Center
City
Akron
State/Province
Ohio
ZIP/Postal Code
44304
Country
United States
Facility Name
Cleveland Clinic Akron General
City
Akron
State/Province
Ohio
ZIP/Postal Code
44307
Country
United States
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic Cancer Center/Fairview Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44111
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Cleveland Clinic Cancer Center Independence
City
Independence
State/Province
Ohio
ZIP/Postal Code
44131
Country
United States
Facility Name
UH Seidman Cancer Center at Southwest General Hospital
City
Middleburg Heights
State/Province
Ohio
ZIP/Postal Code
44130
Country
United States
Facility Name
University Hospitals Parma Medical Center
City
Parma
State/Province
Ohio
ZIP/Postal Code
44129
Country
United States
Facility Name
Cleveland Clinic Cancer Center Strongsville
City
Strongsville
State/Province
Ohio
ZIP/Postal Code
44136
Country
United States
Facility Name
UHHS-Westlake Medical Center
City
Westlake
State/Province
Ohio
ZIP/Postal Code
44145
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Legacy Mount Hood Medical Center
City
Gresham
State/Province
Oregon
ZIP/Postal Code
97030
Country
United States
Facility Name
Legacy Good Samaritan Hospital and Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
Abington Memorial Hospital
City
Abington
State/Province
Pennsylvania
ZIP/Postal Code
19001
Country
United States
Facility Name
Crozer-Keystone Regional Cancer Center at Broomall
City
Broomall
State/Province
Pennsylvania
ZIP/Postal Code
19008
Country
United States
Facility Name
Bryn Mawr Hospital
City
Bryn Mawr
State/Province
Pennsylvania
ZIP/Postal Code
19010
Country
United States
Facility Name
Christiana Care Health System-Concord Health Center
City
Chadds Ford
State/Province
Pennsylvania
ZIP/Postal Code
19317
Country
United States
Facility Name
Geisinger Medical Center
City
Danville
State/Province
Pennsylvania
ZIP/Postal Code
17822
Country
United States
Facility Name
Northeast Radiation Oncology Center
City
Dunmore
State/Province
Pennsylvania
ZIP/Postal Code
18512
Country
United States
Facility Name
Crozer Regional Cancer Center at Brinton Lake
City
Glen Mills
State/Province
Pennsylvania
ZIP/Postal Code
19342
Country
United States
Facility Name
Riddle Memorial Hospital
City
Media
State/Province
Pennsylvania
ZIP/Postal Code
19063
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Aria Health-Torresdale Campus
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19114
Country
United States
Facility Name
Temple University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Reading Hospital
City
West Reading
State/Province
Pennsylvania
ZIP/Postal Code
19611
Country
United States
Facility Name
Geisinger Wyoming Valley/Henry Cancer Center
City
Wilkes-Barre
State/Province
Pennsylvania
ZIP/Postal Code
18711
Country
United States
Facility Name
Lankenau Medical Center
City
Wynnewood
State/Province
Pennsylvania
ZIP/Postal Code
19096
Country
United States
Facility Name
Greenville Health System Cancer Institute-Faris
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Greenville Health System Cancer Institute-Eastside
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Self Regional Healthcare
City
Greenwood
State/Province
South Carolina
ZIP/Postal Code
29646
Country
United States
Facility Name
The Radiation Oncology Center-Hilton Head/Bluffton
City
Hilton Head Island
State/Province
South Carolina
ZIP/Postal Code
29926
Country
United States
Facility Name
Greenville Health System Cancer Institute-Spartanburg
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29307
Country
United States
Facility Name
Sanford USD Medical Center - Sioux Falls
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57117-5134
Country
United States
Facility Name
Vanderbilt University/Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas Medical Branch
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555-0565
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
UTMB Cancer Center at Victory Lakes
City
League City
State/Province
Texas
ZIP/Postal Code
77573
Country
United States
Facility Name
Ogden Regional Medical Center
City
Ogden
State/Province
Utah
ZIP/Postal Code
84405
Country
United States
Facility Name
Huntsman Cancer Institute/University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Norris Cotton Cancer Center-North
City
Saint Johnsbury
State/Province
Vermont
ZIP/Postal Code
05819
Country
United States
Facility Name
Virginia Commonwealth University/Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Virginia Mason Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
City
Yakima
State/Province
Washington
ZIP/Postal Code
98902
Country
United States
Facility Name
West Virginia University Healthcare
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
Wheeling Hospital/Schiffler Cancer Center
City
Wheeling
State/Province
West Virginia
ZIP/Postal Code
26003
Country
United States
Facility Name
Langlade Hospital and Cancer Center
City
Antigo
State/Province
Wisconsin
ZIP/Postal Code
54409
Country
United States
Facility Name
Mayo Clinic Health System-Eau Claire Clinic
City
Eau Claire
State/Province
Wisconsin
ZIP/Postal Code
54701
Country
United States
Facility Name
Aurora Cancer Care-Grafton
City
Grafton
State/Province
Wisconsin
ZIP/Postal Code
53024
Country
United States
Facility Name
Aurora BayCare Medical Center
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54311
Country
United States
Facility Name
UW Cancer Center Johnson Creek
City
Johnson Creek
State/Province
Wisconsin
ZIP/Postal Code
53038
Country
United States
Facility Name
Aurora Cancer Care-Kenosha South
City
Kenosha
State/Province
Wisconsin
ZIP/Postal Code
53142
Country
United States
Facility Name
Gundersen Lutheran Medical Center
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
Facility Name
Mayo Clinic Health System-Franciscan Healthcare
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Community Memorial Hospital
City
Menomonee Falls
State/Province
Wisconsin
ZIP/Postal Code
53051
Country
United States
Facility Name
Ascension Columbia Saint Mary's Water Tower Medical Commons
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53211
Country
United States
Facility Name
Aurora Saint Luke's Medical Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53215
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Aurora Sinai Medical Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53233
Country
United States
Facility Name
Zablocki Veterans Administration Medical Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53295
Country
United States
Facility Name
Vince Lombardi Cancer Clinic - Oshkosh
City
Oshkosh
State/Province
Wisconsin
ZIP/Postal Code
54904
Country
United States
Facility Name
Marshfield Clinic Stevens Point Center
City
Stevens Point
State/Province
Wisconsin
ZIP/Postal Code
54482
Country
United States
Facility Name
Aurora Medical Center in Summit
City
Summit
State/Province
Wisconsin
ZIP/Postal Code
53066
Country
United States
Facility Name
Vince Lombardi Cancer Clinic-Two Rivers
City
Two Rivers
State/Province
Wisconsin
ZIP/Postal Code
54241
Country
United States
Facility Name
Aspirus Regional Cancer Center
City
Wausau
State/Province
Wisconsin
ZIP/Postal Code
54401
Country
United States
Facility Name
Aurora West Allis Medical Center
City
West Allis
State/Province
Wisconsin
ZIP/Postal Code
53227
Country
United States
Facility Name
Diagnostic and Treatment Center
City
Weston
State/Province
Wisconsin
ZIP/Postal Code
54476
Country
United States
Facility Name
Aspirus UW Cancer Center
City
Wisconsin Rapids
State/Province
Wisconsin
ZIP/Postal Code
54494
Country
United States
Facility Name
CHUM - Hopital Notre-Dame
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
Facility Name
McGill University Department of Oncology
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1S6
Country
Canada
Facility Name
CHUM - Centre Hospitalier de l'Universite de Montreal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 3E4
Country
Canada
Facility Name
The Research Institute of the McGill University Health Centre (MUHC)
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3H 2R9
Country
Canada
Facility Name
CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1R 2J6
Country
Canada
Facility Name
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Facility Name
Allan Blair Cancer Centre
City
Regina
State/Province
Saskatchewan
ZIP/Postal Code
S4T 7T1
Country
Canada
Facility Name
Saskatoon Cancer Centre
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 4H4
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
32058845
Citation
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.
Results Reference
result
Available IPD and Supporting Information:
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://nctn-data-archive.nci.nih.gov/
Available IPD/Information Identifier
NCT02360215
Available IPD/Information Comments
Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.
Learn more about this trial
Memantine Hydrochloride and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Reducing Neurocognitive Decline in Patients With Brain Metastases
We'll reach out to this number within 24 hrs