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Trial record 4 of 60 for:    PASSAGE | West Virginia, United States

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02360215
Recruitment Status : Completed
First Posted : February 10, 2015
Results First Posted : March 6, 2020
Last Update Posted : June 2, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Supportive Care
Conditions Cognitive Impairment
Metastatic Malignant Neoplasm in the Brain
Solid Neoplasm
Interventions Radiation: Whole brain radiation therapy with hippocampal avoidance
Drug: Memantine
Radiation: Whole brain radiation therapy
Enrollment 518
Recruitment Details  
Pre-assignment Details Registered patients who completed required baseline neurocognitive assessments were randomized. Of 561 registered patients, 518 were randomized.
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description Whole brain radiation therapy (WBRT) and memantine Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Period Title: Overall Study
Started 257 261
All Randomized Participants 257 261
Started Protocol Treatment 232 223
MDASI-BT Symptom Score [1] 249 251
MDASI-BT Intererence Score [2] 248 251
MDASI-BT Cognitive Factor Score [3] 249 251
MDASI-BT Neurologic Factor Score [4] 249 251
HVLT-R Total Recall [5] 256 259
HVLT-R Delayed Recall [6] 256 259
HVLT-R Recognition [7] 255 259
Trail Making Test (TMT) Part A [8] 256 260
TMT Part B [9] 250 257
Controlled Oral Word Association (COWA) [10] 257 261
Clinical Trial Battery Composite Score [11] 255 259
EQ-5D-5L Index at 2 Months [12] 142 125
EQ-5D-5L Index at 4 Months [13] 110 96
EQ-5D-5L Index at 6 Months [14] 79 70
EQ-5D-5L Index at 12 Months [15] 56 45
EQ-5D-5L VAS at 2 Months [16] 139 123
EQ-5D-5L VAS at 4 Months [17] 104 193
EQ-5D-5L VAS at 6 Months [18] 76 69
EQ-5D-5L VAS at 12 Months [19] 57 48
Completed [20] 257 261
Not Completed 0 0
[1]
M.D. Anderson Symptom Inventory-Brain Module (MDASI-BT) baseline symptom severity subscale completed
[2]
MDSAI-BT symptom interference subscale completed at baseline
[3]
MDSAI-BT cognifitive factor subscale completed at baseline
[4]
MDSAI-BT neurologic factor subscale completed at baseline
[5]
Has standardized baseline Hopkins Verbal Learning Test - Revised (HVLT-R) Total Recall score
[6]
Has standardized baseline HVLT-R Delayed Recall score
[7]
Has standardized baseline HVLT-R Recognition score
[8]
Has standardized baseline TMT Part A score
[9]
Has standardized baseline TMT Part B score
[10]
Has standardized baseline COWA score
[11]
Has standarized baseline Clinical Trial Battery Composite (CTB COMP) score
[12]
EQ-5D-5L index score completed at baseline and 2 months from treatment start
[13]
EQ-5D-5L index score completed at baseline and 4 months from treatment start
[14]
EQ-5D-5L index score completed at baseline and 6 months from treatment start
[15]
EQ-5D-5L index score completed at baseline and 12 months from treatment start
[16]
EQ-5D-5L visual analogue scale (VAS) completed at baseline and 2 months from treatment start
[17]
EQ-5D-5L visual analogue scale (VAS) completed at baseline and 4 months from treatment start
[18]
EQ-5D-5L visual analogue scale (VAS) completed at baseline and 6 months from treatment start
[19]
EQ-5D-5L visual analogue scale (VAS) completed at baseline and 12 months from treatment start
[20]
Subjects contributing data to results are considered to have completed the study.
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine Total
Hide Arm/Group Description Whole brain radiation therapy (WBRT) and memantine Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine Total of all reporting groups
Overall Number of Baseline Participants 257 261 518
Hide Baseline Analysis Population Description
All randomized patients
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 257 participants 261 participants 518 participants
61
(20 to 88)
62
(27 to 91)
61.5
(20 to 91)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 261 participants 518 participants
Female
149
  58.0%
150
  57.5%
299
  57.7%
Male
108
  42.0%
111
  42.5%
219
  42.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 261 participants 518 participants
Hispanic or Latino
5
   1.9%
9
   3.4%
14
   2.7%
Not Hispanic or Latino
231
  89.9%
229
  87.7%
460
  88.8%
Unknown or Not Reported
21
   8.2%
23
   8.8%
44
   8.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 261 participants 518 participants
American Indian or Alaska Native
1
   0.4%
2
   0.8%
3
   0.6%
Asian
4
   1.6%
3
   1.1%
7
   1.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
23
   8.9%
29
  11.1%
52
  10.0%
White
206
  80.2%
205
  78.5%
411
  79.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
23
   8.9%
22
   8.4%
45
   8.7%
Primary tumor  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 261 participants 518 participants
Bone
1
   0.4%
1
   0.4%
2
   0.4%
Breast
45
  17.5%
51
  19.5%
96
  18.5%
Colon
6
   2.3%
4
   1.5%
10
   1.9%
Esophagus
7
   2.7%
6
   2.3%
13
   2.5%
Gastroesophageal Junction
1
   0.4%
1
   0.4%
2
   0.4%
Kidney
8
   3.1%
5
   1.9%
13
   2.5%
Lung
151
  58.8%
156
  59.8%
307
  59.3%
Ovary
3
   1.2%
3
   1.1%
6
   1.2%
Skin
7
   2.7%
15
   5.7%
22
   4.2%
Analcanal
2
   0.8%
1
   0.4%
3
   0.6%
Pancreas
1
   0.4%
1
   0.4%
2
   0.4%
Other
25
   9.7%
17
   6.5%
42
   8.1%
Karnofsky Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 261 participants 518 participants
70
53
  20.6%
48
  18.4%
101
  19.5%
80
75
  29.2%
81
  31.0%
156
  30.1%
90
95
  37.0%
85
  32.6%
180
  34.7%
100
34
  13.2%
47
  18.0%
81
  15.6%
[1]
Measure Description: 70 = Cares for self; unable to carry on normal activity or to do active work; 80 = Normal activity with effort; some signs or symptoms of disease; 90 = Able to carry on normal activity, minor signs or symptoms of disease; 100 = Normal no complaints; no evidence of disease.
Neurologic Function Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 261 participants 518 participants
No neurologic symptoms, FA without assistance
119
  46.3%
113
  43.3%
232
  44.8%
Minor neurologic symptoms, FA without assistance
86
  33.5%
92
  35.2%
178
  34.4%
Moderate NS, FA but requires assistance
27
  10.5%
24
   9.2%
51
   9.8%
Moderate NS, less than FA and requires assistance
15
   5.8%
18
   6.9%
33
   6.4%
Unknown
9
   3.5%
13
   5.0%
22
   4.2%
Not Reported
1
   0.4%
1
   0.4%
2
   0.4%
[1]
Measure Description: NS = neurologic symptoms; FA = fully active at home/work
Recursive Partitioning Analysis (RPA) Class   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 261 participants 518 participants
Class I
38
  14.8%
33
  12.6%
71
  13.7%
Class II
219
  85.2%
228
  87.4%
447
  86.3%
[1]
Measure Description: The Radiation Therapy Oncology Group (RTOG) previously developed three prognostic classes for patients with brain metastases using recursive partitioning analysis (RPA) of a large database. (This study only includes the first two classes.) Class I = Karnofsky Performance Status (KPS) ≥ 70, primary controlled, age < 65, metastasis in brain only. Class II = KPS ≥ 70 and 1 of the following: primary uncontrolled; primary controlled, age ≥ 65; primary controlled, age < 65, metastases in brain & other sites.
Prior Radiosurgery  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 261 participants 518 participants
No
197
  76.7%
200
  76.6%
397
  76.6%
Yes
60
  23.3%
61
  23.4%
121
  23.4%
Prior Surgical Resection  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 261 participants 518 participants
No
189
  73.5%
198
  75.9%
387
  74.7%
Yes
68
  26.5%
63
  24.1%
131
  25.3%
Metastases  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 261 participants 518 participants
Brain
98
  38.1%
98
  37.5%
196
  37.8%
Brain and Other Sites
159
  61.9%
163
  62.5%
322
  62.2%
Education  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 257 participants 261 participants 518 participants
No formal education
1
   0.4%
1
   0.4%
2
   0.4%
Grade school
9
   3.5%
5
   1.9%
14
   2.7%
Not high education graduate
15
   5.8%
22
   8.4%
37
   7.1%
High school graduate (including equivalency)
86
  33.5%
85
  32.6%
171
  33.0%
Some college or associate degree
68
  26.5%
71
  27.2%
139
  26.8%
Bachelor's Degree
43
  16.7%
38
  14.6%
81
  15.6%
Master's Degree
17
   6.6%
22
   8.4%
39
   7.5%
Doctoral degree or professional degree
5
   1.9%
8
   3.1%
13
   2.5%
Not reported
13
   5.1%
9
   3.4%
22
   4.2%
1.Primary Outcome
Title Time to Neurocognitive Failure
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 257 261
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
68.2
(61.2 to 74.2)
59.3
(51.9 to 66.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments Null hypothesis: the addition of HA-WBRT as compared to WBRT will increase time to neurocognitive failure from 53.8% in the WBRT arm to 42.8% in the HA-WBRT arm at 6 months. Treating death as a competing risk and using a Gray's test with two-sided α=0.05 to test for statistically significant difference in the distribution of neurocognitive failure times, it was calculated that 230 events over both arms would provide 90% statistical power.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method Gray's test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.59 to 0.96
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall Score (Neurocognitive Decline)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with standardized score at baseline
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 149 129
Mean (Standard Deviation)
Unit of Measure: units on a scale
2 months Number Analyzed 149 participants 129 participants
-0.63  (1.25) -0.47  (1.21)
4 months Number Analyzed 110 participants 93 participants
-0.68  (1.29) -0.36  (1.16)
6 months Number Analyzed 82 participants 68 participants
-0.34  (1.33) -0.06  (1.14)
12 months Number Analyzed 60 participants 46 participants
-0.55  (1.52) -0.34  (1.34)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with HVLT-R Symptom Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Treatment Arm (WBRT+Memantine vs. HA-WBRT Memantine) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0586
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with HVLT-R Symptom Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Age (>61 year vs. <= 61 years) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0048
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with HVLT-R Symptom Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Baseline Total Recall is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
3.Secondary Outcome
Title Change From Baseline in the Hopkins Verbal Learning Test -Revised (HVLT-R) Delayed Recall Score (Neurocognitive Decline)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with standardized score at baseline
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 256 259
Mean (Standard Deviation)
Unit of Measure: units on a scale
2 months Number Analyzed 148 participants 128 participants
-0.75  (1.51) -0.73  (1.53)
4 months Number Analyzed 109 participants 93 participants
-0.88  (1.61) -0.68  (1.44)
6 months Number Analyzed 80 participants 68 participants
-0.54  (1.55) -0.30  (1.31)
12 months Number Analyzed 60 participants 46 participants
-0.89  (1.65) -0.87  (1.71)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with HVLT-R Delayed Recall Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Treatment Arm (WBRT+Memantine vs. HA-WBRT Memantine) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2656
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with HVLT-R Delayed Recall Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Age (> 61 years vs. <= 61 years) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0067
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with HVLT-R Delayed Recall Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Baseline Delayed Recall is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
4.Secondary Outcome
Title Change From Baseline in the Hopkins Verbal Learning Test -Revised (HVLT-R) Delayed Recognition (Neurocognitive Decline)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with baseline data
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 256 259
Mean (Standard Deviation)
Unit of Measure: units on a scale
2 months Number Analyzed 148 participants 126 participants
-0.69  (1.90) -0.70  (1.88)
4 months Number Analyzed 109 participants 93 participants
-0.11  (1.98) -0.12  (1.41)
6 months Number Analyzed 80 participants 68 participants
-0.55  (1.83) -0.06  (1.40)
12 months Number Analyzed 60 participants 46 participants
-0.48  (2.12) -0.30  (1.65)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with HVLT-R Delayed Recognition Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Treatment Arm (WBRT+Memantine vs. HA-WBRT Memantine) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0993
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with HVLT-R Delayed Recognition Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Age (> 61 years vs. <= 61 years) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with HVLT-R Delayed Recognition Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Baseline Delayed Recognition is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
5.Secondary Outcome
Title Change From Baseline in the Trail Making Test (TMT) Part A (Neurocognitive Decline)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with standardized score at baseline
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 256 260
Mean (Standard Deviation)
Unit of Measure: units on a scale
2 months Number Analyzed 148 participants 130 participants
-1.42  (6.27) -1.31  (5.47)
4 months Number Analyzed 109 participants 93 participants
-0.28  (2.42) 0.03  (2.80)
6 months Number Analyzed 82 participants 68 participants
-2.09  (13.02) 0.17  (2.19)
12 months Number Analyzed 60 participants 47 participants
-1.28  (5.10) -0.70  (3.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with TMT Part A (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Treatment Arm (WBRT+Memantine vs. HA-WBRT Memantine) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5988
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with TMT Part A (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Age (> 61 years vs. <= 61 years) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with TMT Part A (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Baseline TMT Part A is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method McNemar
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
6.Secondary Outcome
Title Change From Baseline in the Trail Making Test (TMT) Part B (Neurocognitive Decline)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with baseline data
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 250 257
Mean (Standard Deviation)
Unit of Measure: units on a scale
2 months Number Analyzed 138 participants 125 participants
-2.86  (16.60) -2.27  (9.91)
4 months Number Analyzed 99 participants 90 participants
-3.38  (17.88) -0.89  (6.14)
6 months Number Analyzed 78 participants 67 participants
-0.47  (7.78) -1.06  (6.55)
12 months Number Analyzed 58 participants 46 participants
-2.49  (8.18) -1.44  (6.59)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with TMT Part B (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Treatment Arm (WBRT+Memantine vs. HA-WBRT Memantine) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9226
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with TMT Part B (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Age (> 61 years vs. <= 61 years) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0024
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with TMT Part B (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Baseline TMT Part B is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Cox
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
7.Secondary Outcome
Title Change From Baseline in the Controlled Oral Word Association (COWA) Test (Neurocognitive Decline)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with standardized score at baseline
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 257 261
Mean (Standard Deviation)
Unit of Measure: units on a scale
2 months Number Analyzed 149 participants 128 participants
-0.28  (0.96) -0.29  (1.04)
4 months Number Analyzed 108 participants 95 participants
-0.06  (0.98) -0.08  (0.99)
6 months Number Analyzed 81 participants 68 participants
-0.15  (0.87) -0.11  (1.04)
12 months Number Analyzed 80 participants 68 participants
-0.44  (1.71) -0.21  (1.65)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with COWA (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Baseline COWA is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with COWA (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Treatment Arm (WBRT+Memantine vs. HA-WBRT Memantine) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9749
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with COWA (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Age (> 61 years vs. <= 61 years) is reported here. is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
8.Secondary Outcome
Title Change From Baseline in the Clinical Trial Battery Composite (CTB COMP) Score [Neurocognitive Decline]
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with standardized score at baseline
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 255 259
Mean (Standard Deviation)
Unit of Measure: units on a scale
2 months Number Analyzed 148 participants 127 participants
-1.09  (3.45) -0.87  (2.35)
4 months Number Analyzed 107 participants 92 participants
-0.81  (3.22) -0.27  (1.66)
6 months Number Analyzed 80 participants 68 participants
-0.44  (1.71) -0.21  (1.65)
12 months Number Analyzed 60 participants 46 participants
-0.98  (2.51) -0.61  (2.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with the neurocognitive composite score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Treatment Arm (WBRT+Memantine vs. HA-WBRT Memantine) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2552
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with the neurocognitive composite score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Age (> 61 years vs. <= 61 years) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with the neurocognitive composite score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Baseline composite score is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
9.Secondary Outcome
Title Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with baseline data
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 249 251
Mean (Standard Deviation)
Unit of Measure: score on a scale
2 months Number Analyzed 146 participants 126 participants
0.48  (1.39) 0.61  (1.62)
4 months Number Analyzed 113 participants 99 participants
0.29  (1.50) 0.36  (1.46)
6 months Number Analyzed 81 participants 71 participants
0.24  (1.49) -0.09  (1.34)
12 months Number Analyzed 61 participants 47 participants
0.53  (1.69) 0.09  (1.47)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with MDASI-BT Symptom Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Treatment Arm (WBRT+Memantine vs. HA-WBRT Memantine) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with MDASI-BT Symptom Severity score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Baseline symptom severity is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A two-sample t-test with a 2-sided type I error of 0.05 provides >90% statistical power to detect a medium effect size of 0.5 for a comparison of the change from baseline to 6 months from the start of treatment. The comparison at six months was tested within a mixed effects model with covariates age, RPA class, prior radiosurgery, prior surgical resection, baseline score, treatment arm, and time was used.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.083
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
10.Secondary Outcome
Title Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Interference Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with baseline data
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 248 251
Mean (Standard Deviation)
Unit of Measure: score on a scale
2 months Number Analyzed 143 participants 124 participants
0.84  (2.45) 1.09  (2.79)
4 months Number Analyzed 112 participants 99 participants
0.35  (2.57) 0.51  (2.60)
6 months Number Analyzed 81 participants 71 participants
0.57  (2.61) 0.01  (2.72)
12 months Number Analyzed 60 participants 47 participants
0.64  (2.86) 0.14  (3.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with MDASI-BT Interference Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Treatment Arm (WBRT+Memantine vs. HA-WBRT Memantine) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9118
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with MDASI-BT Interference Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Baseline interference score is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
11.Secondary Outcome
Title Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Factor Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with baseline data
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 249 251
Mean (Standard Deviation)
Unit of Measure: score on a scale
2 months Number Analyzed 146 participants 125 participants
0.45  (1.81) 0.50  (1.95)
4 months Number Analyzed 113 participants 99 participants
0.52  (1.64) 0.32  (1.78)
6 months Number Analyzed 81 participants 71 participants
0.57  (2.61) 0.01  (2.72)
12 months Number Analyzed 61 participants 47 participants
1.04  (2.33) 0.50  (1.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with MDASI-BT Cognitive Factor Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Treatment Arm (WBRT+Memantine vs. HA-WBRT Memantine) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1964
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with MDASI-BT Cognitive Factor Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Baseline cognitive factor score is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with MDASI-BT Cognitive Factor Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Prior radiotherapy (yes vs. no) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0032
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
12.Secondary Outcome
Title Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Neurologic Factor Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with baseline data
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 249 251
Mean (Standard Deviation)
Unit of Measure: score on a scale
2 months Number Analyzed 146 participants 124 participants
0.17  (1.91) 0.28  (2.31)
4 months Number Analyzed 113 participants 99 participants
0.13  (2.06) 0.24  (1.97)
6 months Number Analyzed 81 participants 71 participants
0.23  (1.89) 0.15  (2.11)
12 months Number Analyzed 61 participants 47 participants
0.60  (2.20) 0.40  (2.53)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with MDASI-BT Neurologic Factor Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Treatment Arm (WBRT+Memantine vs. HA-WBRT Memantine) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8877
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with MDASI-BT Neurologic Factor Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Baseline neurologic factor is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments A mixed effects model was run with MDASI-BT Neurologic Factor Score (baseline, 2, 4, 6, and 12 months) as the outcome of interest. Age, RPA class, prior radiosurgery, prior surgical resection were the covariates considered in each model along with interaction terms treatment*time, time*time, time*time*time and remained if p<0.05. Baseline score, treatment arm, and time were forced into the model. Age (> 61 years vs. <= 61 years) is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0078
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept estimates are not shown.)
13.Secondary Outcome
Title Change in EQ-5D-5L Index Score at 2 Months
Hide 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
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Participants with baseline and 2-month scores
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
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Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 142 125
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.04  (0.17) -0.05  (0.16)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.86
Comments Significance level = 0.05
Method t-test, 2 sided
Comments [Not Specified]
14.Secondary Outcome
Title Change in EQ-5D-5L Index Score at 4 Months
Hide 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
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Participants with baseline and 4-month scores
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
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Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 110 96
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.03  (0.17) -0.03  (0.16)
15.Secondary Outcome
Title Change in EQ-5D-5L Index Score at 6 Months
Hide 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
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Participants with baseline and 4-month scores
Arm/Group Title HA-WBRT + Memantine WBRT + Memantin
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 79 70
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.03  (0.14) -0.03  (0.17)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantin
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.95
Comments Significance level = 0.05
Method t-test, 2 sided
Comments [Not Specified]
16.Secondary Outcome
Title Change in EQ-5D-5L Index Score at 12 Months
Hide 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
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Participants with baseline and 12-month scores
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 56 45
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.03  (0.17) -0.01  (0.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.66
Comments Significance level = 0.05
Method t-test, 2 sided
Comments [Not Specified]
17.Secondary Outcome
Title Change in EQ-5D-5L VAS Score at 2 Months
Hide 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
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Participants with baseline and 2-month scores
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
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Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 139 123
Mean (Standard Deviation)
Unit of Measure: score on a scale
-5.64  (24.67) -1.41  (25.79)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments Significance level = 0.05
Method t-test, 2 sided
Comments [Not Specified]
18.Secondary Outcome
Title Change in EQ-5D-5L VAS Score at 4 Months
Hide 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
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Participants with baseline and 4-month scores
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
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Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 104 93
Mean (Standard Deviation)
Unit of Measure: score on a scale
-1.35  (23.14) -2.98  (25.71)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.64
Comments Significance level = 0.05
Method t-test, 2 sided
Comments [Not Specified]
19.Secondary Outcome
Title Change in EQ-5D-5L VAS Score at 6 Months
Hide 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
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Participants with baseline and 6-month scores
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 76 69
Mean (Standard Deviation)
Unit of Measure: score on a scale
3.97  (25.33) 3.49  (22.90)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.91
Comments Significance level = 0.05
Method t-test, 2 sided
Comments [Not Specified]
20.Secondary Outcome
Title Change in EQ-5D-5L VAS Score at 12 Months
Hide 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
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Participants with baseline and 6-month scores
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 57 48
Mean (Standard Deviation)
Unit of Measure: score on a scale
2.86  (19.60) 2.42  (23.37)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.92
Comments Significance level = 0.05
Method t-test, 2 sided
Comments [Not Specified]
21.Secondary Outcome
Title Intracranial Progression-Free Survival
Hide 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.
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All randomized participants
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 257 261
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
43.9
(37.5 to 50.2)
44.8
(38.5 to 51.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.076
Comments Two-sided significance level = 0.05
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.98 to 1.47
Estimation Comments Reference level = WBRT + Memantine
22.Secondary Outcome
Title Overall Survival
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
Hide Arm/Group Description:
Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 257 261
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
54.9
(48.6 to 61.2)
50.6
(44.2 to 57.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.242
Comments Two-sided significance level = 0.05
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.91 to 1.43
Estimation Comments Reference level = WBRT + Memantin
23.Secondary Outcome
Title Number of Patients With a Grade 3+ Adverse Event (AE) Regardless of Relationship to Treatment
Hide 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.
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Randomized participants who started protocol treatment
Arm/Group Title HA-WBRT + Memantine WBRT + Memantine
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Whole brain radiation therapy (WBRT) and memantine
Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
Overall Number of Participants Analyzed 232 223
Measure Type: Count of Participants
Unit of Measure: Participants
144
  62.1%
131
  58.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HA-WBRT + Memantine, WBRT + Memantine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments Two-sided p-value = 0.05
Method Chi-squared
Comments [Not Specified]
24.Other Pre-specified Outcome
Title Anxiety/Depression Measured Using the EQ-5D-5L
Hide 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
Outcome Measure Data Not Reported
25.Other Pre-specified Outcome
Title Effect of Radiation Therapy Oncology Group (RTOG) RPA and the Diagnosis-specific Graded Prognostic Assessment (DSGPA) on Neurocognitive Function
Hide 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
Outcome Measure Data Not Reported
26.Other Pre-specified Outcome
Title Effect of White Matter Injury and Hippocampal Volume on Neurocognitive Function
Hide 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
Outcome Measure Data Not Reported
27.Other Pre-specified Outcome
Title MDASI-BT Mood Variables
Hide Description The relationship between EQ-5D-5L and MDASI-BT mood variables and neurocognitive function will be assessed.
Time Frame Up to 12 months
Outcome Measure Data Not Reported
Time Frame From randomization to last follow-up. Maximum follow-up was 15.6 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title HA-WBRT + Memantine WBRT + Memantin
Hide Arm/Group Description Whole brain radiation therapy (WBRT) and memantine Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) and memantine
All-Cause Mortality
HA-WBRT + Memantine WBRT + Memantin
Affected / at Risk (%) Affected / at Risk (%)
Total   138/232 (59.48%)   135/223 (60.54%) 
Hide Serious Adverse Events
HA-WBRT + Memantine WBRT + Memantin
Affected / at Risk (%) Affected / at Risk (%)
Total   98/232 (42.24%)   106/222 (47.75%) 
Blood and lymphatic system disorders     
Anemia * 1  3/232 (1.29%)  5/222 (2.25%) 
Febrile neutropenia * 1  0/232 (0.00%)  1/222 (0.45%) 
Cardiac disorders     
Atrial fibrillation * 1  1/232 (0.43%)  1/222 (0.45%) 
Cardiac disorders - Other * 1  2/232 (0.86%)  0/222 (0.00%) 
Pericardial effusion * 1  1/232 (0.43%)  1/222 (0.45%) 
Pericardial tamponade * 1  0/232 (0.00%)  1/222 (0.45%) 
Sinus tachycardia * 1  1/232 (0.43%)  2/222 (0.90%) 
Endocrine disorders     
Cushingoid * 1  0/232 (0.00%)  1/222 (0.45%) 
Endocrine disorders - Other * 1  2/232 (0.86%)  0/222 (0.00%) 
Eye disorders     
Blurred vision * 1  1/232 (0.43%)  1/222 (0.45%) 
Gastrointestinal disorders     
Abdominal distension * 1  1/232 (0.43%)  0/222 (0.00%) 
Abdominal pain * 1  1/232 (0.43%)  3/222 (1.35%) 
Ascites * 1  1/232 (0.43%)  0/222 (0.00%) 
Bloating * 1  0/232 (0.00%)  1/222 (0.45%) 
Colitis * 1  0/232 (0.00%)  2/222 (0.90%) 
Constipation * 1  3/232 (1.29%)  2/222 (0.90%) 
Diarrhea * 1  0/232 (0.00%)  2/222 (0.90%) 
Dyspepsia * 1  0/232 (0.00%)  1/222 (0.45%) 
Dysphagia * 1  0/232 (0.00%)  4/222 (1.80%) 
Enterocolitis * 1  0/232 (0.00%)  1/222 (0.45%) 
Esophageal hemorrhage * 1  1/232 (0.43%)  0/222 (0.00%) 
Esophageal obstruction * 1  0/232 (0.00%)  1/222 (0.45%) 
Esophagitis * 1  0/232 (0.00%)  1/222 (0.45%) 
Gastrointestinal disorders - Other * 1  1/232 (0.43%)  1/222 (0.45%) 
Gastrointestinal pain * 1  1/232 (0.43%)  0/222 (0.00%) 
Ileus * 1  1/232 (0.43%)  1/222 (0.45%) 
Lower gastrointestinal hemorrhage * 1  1/232 (0.43%)  1/222 (0.45%) 
Nausea * 1  5/232 (2.16%)  4/222 (1.80%) 
Pancreatic hemorrhage * 1  0/232 (0.00%)  1/222 (0.45%) 
Pancreatitis * 1  0/232 (0.00%)  1/222 (0.45%) 
Small intestinal perforation * 1  2/232 (0.86%)  0/222 (0.00%) 
Upper gastrointestinal hemorrhage * 1  1/232 (0.43%)  0/222 (0.00%) 
Vomiting * 1  4/232 (1.72%)  5/222 (2.25%) 
General disorders     
Chills * 1  1/232 (0.43%)  0/222 (0.00%) 
Death NOS * 1  6/232 (2.59%)  9/222 (4.05%) 
Edema limbs * 1  1/232 (0.43%)  1/222 (0.45%) 
Fatigue * 1  1/232 (0.43%)  12/222 (5.41%) 
Fever * 1  2/232 (0.86%)  3/222 (1.35%) 
Flu like symptoms * 1  1/232 (0.43%)  1/222 (0.45%) 
Gait disturbance * 1  1/232 (0.43%)  2/222 (0.90%) 
General disorders and administration site conditions - Other * 1  2/232 (0.86%)  2/222 (0.90%) 
Infusion related reaction * 1  1/232 (0.43%)  0/222 (0.00%) 
Localized edema * 1  0/232 (0.00%)  1/222 (0.45%) 
Multi-organ failure * 1  1/232 (0.43%)  1/222 (0.45%) 
Non-cardiac chest pain * 1  0/232 (0.00%)  1/222 (0.45%) 
Pain * 1  2/232 (0.86%)  4/222 (1.80%) 
Sudden death NOS * 1  1/232 (0.43%)  0/222 (0.00%) 
Hepatobiliary disorders     
Bile duct stenosis * 1  1/232 (0.43%)  0/222 (0.00%) 
Gallbladder obstruction * 1  0/232 (0.00%)  1/222 (0.45%) 
Hepatic failure * 1  0/232 (0.00%)  1/222 (0.45%) 
Hepatic pain * 1  1/232 (0.43%)  0/222 (0.00%) 
Hepatobiliary disorders - Other * 1  1/232 (0.43%)  0/222 (0.00%) 
Immune system disorders     
Allergic reaction * 1  0/232 (0.00%)  1/222 (0.45%) 
Infections and infestations     
Abdominal infection * 1  1/232 (0.43%)  0/222 (0.00%) 
Appendicitis * 1  0/232 (0.00%)  1/222 (0.45%) 
Bone infection * 1  1/232 (0.43%)  1/222 (0.45%) 
Bronchial infection * 1  0/232 (0.00%)  1/222 (0.45%) 
Catheter related infection * 1  1/232 (0.43%)  1/222 (0.45%) 
Encephalitis infection * 1  1/232 (0.43%)  0/222 (0.00%) 
Endocarditis infective * 1  1/232 (0.43%)  0/222 (0.00%) 
Infections and infestations - Other * 1  2/232 (0.86%)  2/222 (0.90%) 
Lung infection * 1  4/232 (1.72%)  7/222 (3.15%) 
Mucosal infection * 1  1/232 (0.43%)  0/222 (0.00%) 
Peritoneal infection * 1  1/232 (0.43%)  0/222 (0.00%) 
Sepsis * 1  8/232 (3.45%)  5/222 (2.25%) 
Small intestine infection * 1  1/232 (0.43%)  0/222 (0.00%) 
Upper respiratory infection * 1  0/232 (0.00%)  1/222 (0.45%) 
Urinary tract infection * 1  4/232 (1.72%)  4/222 (1.80%) 
Wound infection * 1  1/232 (0.43%)  1/222 (0.45%) 
Injury, poisoning and procedural complications     
Fall * 1  1/232 (0.43%)  4/222 (1.80%) 
Wound dehiscence * 1  0/232 (0.00%)  1/222 (0.45%) 
Investigations     
Alanine aminotransferase increased * 1  0/232 (0.00%)  1/222 (0.45%) 
Alkaline phosphatase increased * 1  0/232 (0.00%)  1/222 (0.45%) 
Aspartate aminotransferase increased * 1  0/232 (0.00%)  1/222 (0.45%) 
Blood bilirubin increased * 1  0/232 (0.00%)  1/222 (0.45%) 
Creatinine increased * 1  1/232 (0.43%)  0/222 (0.00%) 
INR increased * 1  1/232 (0.43%)  1/222 (0.45%) 
Investigations - Other * 1  0/232 (0.00%)  2/222 (0.90%) 
Neutrophil count decreased * 1  0/232 (0.00%)  3/222 (1.35%) 
Platelet count decreased * 1  1/232 (0.43%)  2/222 (0.90%) 
Weight loss * 1  0/232 (0.00%)  2/222 (0.90%) 
White blood cell decreased * 1  0/232 (0.00%)  2/222 (0.90%) 
Metabolism and nutrition disorders     
Anorexia * 1  1/232 (0.43%)  2/222 (0.90%) 
Dehydration * 1  2/232 (0.86%)  7/222 (3.15%) 
Hypercalcemia * 1  2/232 (0.86%)  2/222 (0.90%) 
Hyperglycemia * 1  3/232 (1.29%)  1/222 (0.45%) 
Hypocalcemia * 1  0/232 (0.00%)  1/222 (0.45%) 
Hypoglycemia * 1  0/232 (0.00%)  1/222 (0.45%) 
Hypokalemia * 1  1/232 (0.43%)  2/222 (0.90%) 
Hypomagnesemia * 1  0/232 (0.00%)  1/222 (0.45%) 
Hyponatremia * 1  4/232 (1.72%)  4/222 (1.80%) 
Metabolism and nutrition disorders - Other * 1  0/232 (0.00%)  2/222 (0.90%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  4/232 (1.72%)  3/222 (1.35%) 
Bone pain * 1  0/232 (0.00%)  1/222 (0.45%) 
Chest wall pain * 1  0/232 (0.00%)  1/222 (0.45%) 
Generalized muscle weakness * 1  10/232 (4.31%)  7/222 (3.15%) 
Muscle weakness left-sided * 1  1/232 (0.43%)  1/222 (0.45%) 
Muscle weakness lower limb * 1  2/232 (0.86%)  2/222 (0.90%) 
Muscle weakness right-sided * 1  1/232 (0.43%)  1/222 (0.45%) 
Muscle weakness upper limb * 1  0/232 (0.00%)  1/222 (0.45%) 
Musculoskeletal and connective tissue disorder - Other * 1  2/232 (0.86%)  0/222 (0.00%) 
Neck pain * 1  1/232 (0.43%)  0/222 (0.00%) 
Pain in extremity * 1  2/232 (0.86%)  1/222 (0.45%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other * 1  13/232 (5.60%)  9/222 (4.05%) 
Tumor pain * 1  2/232 (0.86%)  1/222 (0.45%) 
Nervous system disorders     
Ataxia * 1  0/232 (0.00%)  1/222 (0.45%) 
Cognitive disturbance * 1  1/232 (0.43%)  2/222 (0.90%) 
Depressed level of consciousness * 1  0/232 (0.00%)  1/222 (0.45%) 
Dizziness * 1  1/232 (0.43%)  3/222 (1.35%) 
Dysgeusia * 1  0/232 (0.00%)  1/222 (0.45%) 
Edema cerebral * 1  1/232 (0.43%)  1/222 (0.45%) 
Encephalopathy * 1  2/232 (0.86%)  0/222 (0.00%) 
Headache * 1  5/232 (2.16%)  6/222 (2.70%) 
Hydrocephalus * 1  0/232 (0.00%)  1/222 (0.45%) 
Intracranial hemorrhage * 1  1/232 (0.43%)  2/222 (0.90%) 
Ischemia cerebrovascular * 1  0/232 (0.00%)  1/222 (0.45%) 
Lethargy * 1  1/232 (0.43%)  0/222 (0.00%) 
Memory impairment * 1  0/232 (0.00%)  1/222 (0.45%) 
Movements involuntary * 1  0/232 (0.00%)  1/222 (0.45%) 
Nervous system disorders - Other * 1  5/232 (2.16%)  0/222 (0.00%) 
Paresthesia * 1  0/232 (0.00%)  1/222 (0.45%) 
Peripheral motor neuropathy * 1  0/232 (0.00%)  2/222 (0.90%) 
Peripheral sensory neuropathy * 1  1/232 (0.43%)  1/222 (0.45%) 
Seizure * 1  7/232 (3.02%)  0/222 (0.00%) 
Somnolence * 1  0/232 (0.00%)  1/222 (0.45%) 
Stroke * 1  2/232 (0.86%)  1/222 (0.45%) 
Syncope * 1  1/232 (0.43%)  0/222 (0.00%) 
Psychiatric disorders     
Confusion * 1  6/232 (2.59%)  7/222 (3.15%) 
Delirium * 1  1/232 (0.43%)  2/222 (0.90%) 
Depression * 1  1/232 (0.43%)  0/222 (0.00%) 
Hallucinations * 1  1/232 (0.43%)  0/222 (0.00%) 
Psychiatric disorders - Other * 1  1/232 (0.43%)  1/222 (0.45%) 
Suicidal ideation * 1  2/232 (0.86%)  0/222 (0.00%) 
Renal and urinary disorders     
Acute kidney injury * 1  2/232 (0.86%)  4/222 (1.80%) 
Chronic kidney disease * 1  1/232 (0.43%)  0/222 (0.00%) 
Renal and urinary disorders - Other * 1  1/232 (0.43%)  1/222 (0.45%) 
Renal calculi * 1  1/232 (0.43%)  0/222 (0.00%) 
Urinary incontinence * 1  0/232 (0.00%)  1/222 (0.45%) 
Urinary retention * 1  2/232 (0.86%)  0/222 (0.00%) 
Urinary urgency * 1  1/232 (0.43%)  0/222 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Aspiration * 1  1/232 (0.43%)  1/222 (0.45%) 
Bronchopulmonary hemorrhage * 1  1/232 (0.43%)  0/222 (0.00%) 
Cough * 1  0/232 (0.00%)  1/222 (0.45%) 
Dyspnea * 1  5/232 (2.16%)  9/222 (4.05%) 
Hypoxia * 1  1/232 (0.43%)  3/222 (1.35%) 
Pleural effusion * 1  4/232 (1.72%)  3/222 (1.35%) 
Pleuritic pain * 1  0/232 (0.00%)  1/222 (0.45%) 
Pneumonitis * 1  1/232 (0.43%)  2/222 (0.90%) 
Pneumothorax * 1  0/232 (0.00%)  1/222 (0.45%) 
Respiratory failure * 1  1/232 (0.43%)  6/222 (2.70%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  0/232 (0.00%)  1/222 (0.45%) 
Skin and subcutaneous tissue disorders - Other * 1  1/232 (0.43%)  0/222 (0.00%) 
Skin ulceration * 1  0/232 (0.00%)  1/222 (0.45%) 
Surgical and medical procedures     
Surgical and medical procedures - Other * 1  0/232 (0.00%)  1/222 (0.45%) 
Vascular disorders     
Hypertension * 1  1/232 (0.43%)  0/222 (0.00%) 
Hypotension * 1  2/232 (0.86%)  2/222 (0.90%) 
Peripheral ischemia * 1  0/232 (0.00%)  1/222 (0.45%) 
Superior vena cava syndrome * 1  1/232 (0.43%)  0/222 (0.00%) 
Thromboembolic event * 1  12/232 (5.17%)  14/222 (6.31%) 
Vascular disorders - Other * 1  0/232 (0.00%)  1/222 (0.45%) 
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
HA-WBRT + Memantine WBRT + Memantin
Affected / at Risk (%) Affected / at Risk (%)
Total   214/232 (92.24%)   201/223 (90.13%) 
Blood and lymphatic system disorders     
Anemia * 1  38/232 (16.38%)  43/223 (19.28%) 
Ear and labyrinth disorders     
Hearing impaired * 1  15/232 (6.47%)  16/223 (7.17%) 
Eye disorders     
Blurred vision * 1  31/232 (13.36%)  23/223 (10.31%) 
Gastrointestinal disorders     
Abdominal pain * 1  25/232 (10.78%)  13/223 (5.83%) 
Constipation * 1  60/232 (25.86%)  41/223 (18.39%) 
Diarrhea * 1  34/232 (14.66%)  19/223 (8.52%) 
Dry mouth * 1  21/232 (9.05%)  18/223 (8.07%) 
Dysphagia * 1  13/232 (5.60%)  14/223 (6.28%) 
Nausea * 1  105/232 (45.26%)  89/223 (39.91%) 
Vomiting * 1  43/232 (18.53%)  34/223 (15.25%) 
General disorders     
Edema limbs * 1  25/232 (10.78%)  18/223 (8.07%) 
Fatigue * 1  157/232 (67.67%)  143/223 (64.13%) 
Gait disturbance * 1  27/232 (11.64%)  22/223 (9.87%) 
Pain * 1  26/232 (11.21%)  28/223 (12.56%) 
Infections and infestations     
Mucosal infection * 1  10/232 (4.31%)  12/223 (5.38%) 
Injury, poisoning and procedural complications     
Dermatitis radiation * 1  18/232 (7.76%)  11/223 (4.93%) 
Fall * 1  15/232 (6.47%)  23/223 (10.31%) 
Investigations     
Alanine aminotransferase increased * 1  11/232 (4.74%)  13/223 (5.83%) 
Alkaline phosphatase increased * 1  10/232 (4.31%)  17/223 (7.62%) 
Aspartate aminotransferase increased * 1  6/232 (2.59%)  12/223 (5.38%) 
Lymphocyte count decreased * 1  22/232 (9.48%)  25/223 (11.21%) 
Platelet count decreased * 1  16/232 (6.90%)  17/223 (7.62%) 
Weight loss * 1  44/232 (18.97%)  31/223 (13.90%) 
White blood cell decreased * 1  13/232 (5.60%)  20/223 (8.97%) 
Metabolism and nutrition disorders     
Anorexia * 1  73/232 (31.47%)  69/223 (30.94%) 
Dehydration * 1  13/232 (5.60%)  15/223 (6.73%) 
Hyperglycemia * 1  14/232 (6.03%)  20/223 (8.97%) 
Hypoalbuminemia * 1  20/232 (8.62%)  18/223 (8.07%) 
Hypocalcemia * 1  14/232 (6.03%)  6/223 (2.69%) 
Hypokalemia * 1  21/232 (9.05%)  18/223 (8.07%) 
Hyponatremia * 1  22/232 (9.48%)  17/223 (7.62%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  28/232 (12.07%)  26/223 (11.66%) 
Generalized muscle weakness * 1  49/232 (21.12%)  42/223 (18.83%) 
Muscle weakness lower limb * 1  11/232 (4.74%)  12/223 (5.38%) 
Pain in extremity * 1  13/232 (5.60%)  6/223 (2.69%) 
Nervous system disorders     
Dizziness * 1  59/232 (25.43%)  51/223 (22.87%) 
Dysgeusia * 1  18/232 (7.76%)  23/223 (10.31%) 
Headache * 1  100/232 (43.10%)  84/223 (37.67%) 
Memory impairment * 1  28/232 (12.07%)  26/223 (11.66%) 
Nervous system disorders - Other * 1  13/232 (5.60%)  7/223 (3.14%) 
Paresthesia * 1  16/232 (6.90%)  13/223 (5.83%) 
Peripheral sensory neuropathy * 1  17/232 (7.33%)  17/223 (7.62%) 
Seizure * 1  16/232 (6.90%)  9/223 (4.04%) 
Tremor * 1  12/232 (5.17%)  18/223 (8.07%) 
Psychiatric disorders     
Anxiety * 1  23/232 (9.91%)  17/223 (7.62%) 
Confusion * 1  26/232 (11.21%)  26/223 (11.66%) 
Depression * 1  25/232 (10.78%)  17/223 (7.62%) 
Insomnia * 1  32/232 (13.79%)  26/223 (11.66%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  45/232 (19.40%)  38/223 (17.04%) 
Dyspnea * 1  50/232 (21.55%)  50/223 (22.42%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  70/232 (30.17%)  54/223 (24.22%) 
Pruritus * 1  13/232 (5.60%)  6/223 (2.69%) 
Vascular disorders     
Hypertension * 1  13/232 (5.60%)  17/223 (7.62%) 
Hypotension * 1  10/232 (4.31%)  12/223 (5.38%) 
Thromboembolic event * 1  13/232 (5.60%)  8/223 (3.59%) 
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Must obtain prior Sponsor approval.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Wendy Seiferheld
Organization: NRG Oncology
Phone: 215-574-3208
EMail: seiferheldw@nrgoncology.org
Layout table for additonal information
Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT02360215    
Other Study ID Numbers: NRG-CC001
NCI-2015-00030 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-CC001 ( Other Identifier: NRG Oncology )
NRG-CC001 ( Other Identifier: DCP )
NRG-CC001 ( Other Identifier: CTEP )
UG1CA189867 ( U.S. NIH Grant/Contract )
First Submitted: February 5, 2015
First Posted: February 10, 2015
Results First Submitted: January 14, 2020
Results First Posted: March 6, 2020
Last Update Posted: June 2, 2021