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Radiation Therapy (RT) and Temozolomide (TMZ) in Treating Patients With Newly Diagnosed Glioblastoma or Gliosarcoma

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: NCT00304031
Recruitment Status : Completed
First Posted : March 17, 2006
Results First Posted : April 30, 2014
Last Update Posted : June 9, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
European Organisation for Research and Treatment of Cancer - EORTC
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Brain and Central Nervous System Tumors
Interventions Drug: Concurrent temozolomide
Radiation: Concurrent radiation therapy
Drug: 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle
Drug: 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle
Enrollment 1173
Recruitment Details  
Pre-assignment Details Sites were required to submit participant tumor tissue for central histologic review and MGMT (O-6-methylguanine-DNA methyltransferase) status determination in order for registered participants to continue on the study. Of 1173 participants initially registered, 1125 participants met these requirements and started protocol treatment.
Arm/Group Title No Adjuvant TMZ (Not Randomized) Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description Concurrent radiation therapy (RT) with concurrent temozolomide (TMZ) (75 mg/m2) up to 49 doses. Not randomized to either adjuvant TMZ arm. Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle. Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle.
Period Title: Concomitant RT+TMZ (Pre-randomization)
Started 1125 [1] 0 [2] 0 [2]
Eligible Pre-randomization Population 1125 0 0
Eligible Pre-randomization Follow-up [3] 1120 0 0
Completed 833 [4] 0 0
Not Completed 292 0 0
Reason Not Completed
Ineligible due to insufficient tissue             144             0             0
Disease progression             48             0             0
Patient refusal             19             0             0
Death             18             0             0
Physician preference             15             0             0
Toxicity             10             0             0
Other complicating disease             1             0             0
Other, not otherwise specified             37             0             0
[1]
All participants registered to concomitant treatment; randomized after completing this treatment.
[2]
Participants were not randomized to adjuvant TMZ until after completion of concomitant treatment.
[3]
Eligible pre-randomization participants with any follow-up data.
[4]
These participants completed concomitant treatment and met requirements for randomization.
Period Title: Randomization to Adjuvant TMZ Arm
Started [1] 0 411 422
Eligible Population 0 411 420
Unmethylated MGMT Population [2] 0 254 262
Methylated MGMT Population [3] 0 122 122
Quality of Life Population [4] 0 96 95
Completed 0 411 [5] 420 [5]
Not Completed 0 0 2
Reason Not Completed
No follow-up collected             0             0             2
[1]
Participants who met requirements after concomitant treatment were randomized to an adjuvant arm.
[2]
Eligible participants determined to have unmethylated MGMT.
[3]
Eligible participants determined to have methylated MGMT.
[4]
Eligible participants who consented to the quality of life study component, offered after 07-12-2007
[5]
Randomized participants contributing data to results are considered to have completed the study.
Arm/Group Title No Adjuvant TMZ (Not Randomized ) Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ Total
Hide Arm/Group Description Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Not randomized to either adjuvant TMZ arm. Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle. Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle. Total of all reporting groups
Overall Number of Baseline Participants 292 411 422 1125
Hide Baseline Analysis Population Description
Eligible patients who were randomized.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 292 participants 411 participants 422 participants 1125 participants
60.5
(22 to 87)
57
(22 to 84)
58
(21 to 84)
58
(21 to 87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 292 participants 411 participants 422 participants 1125 participants
Female
126
  43.2%
172
  41.8%
185
  43.8%
483
  42.9%
Male
166
  56.8%
239
  58.2%
237
  56.2%
642
  57.1%
1.Primary Outcome
Title Median Overall Survival Time
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 occurred after 647 deaths were reported.
Time Frame From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized eligible patients.
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (TMZ) (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle.
Overall Number of Participants Analyzed 411 420
Median (95% Confidence Interval)
Unit of Measure: months
16.6
(14.9 to 18.0)
14.9
(13.7 to 16.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments This study was looking for a 20% reduction in hazard rate: null hypothesis (conventional arm): Median survival time (MST) = 14.0 mo.; alternative hypothesis (dose-dense arm): MST= 17.5 mo. A one-sided log-rank test at a significance level of 0.025 would have 80% power to detect this difference with a sample size of 750 patients (647 deaths were required for the final analysis).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments One-sided
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.88 to 1.20
Estimation Comments Reference level = Conventional adjuvant TMZ
2.Secondary Outcome
Title Median Progression-free Survival (PFS) Time
Hide Description Progression is defined as greater than 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. Progression-free survival time is defined as time from registration to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. A concomitant decrease in steroid dose will rule out a progression designation during the first 2 months after completion of radiation therapy. Analysis occurred after 647 deaths were reported.
Time Frame From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized eligible patients
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle.
Overall Number of Participants Analyzed 411 420
Median (95% Confidence Interval)
Unit of Measure: months
5.5
(4.7 to 6.1)
6.7
(6.2 to 7.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.06
Comments Two-side significance level = 0.05
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.75 to 1.00
Estimation Comments Reference level = Conventional adjuvant TMZ
3.Secondary Outcome
Title Median Overall Survival Time by MGMT Status
Hide Description Overall survival time is defined as time from 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. Tumor tissue submitted at baseline was analyzed to determine MGMT (O[6]-methylguanine-DNA methyltransferase) promoter methylation status (methylated / unmethylated). Analysis occurred after 647 deaths were reported.
Time Frame From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
MGMT status was not available for all randomized eligible participants. Therefore, data was only available from 376/411 on the conventional arm and 384/420 on the dose-dense arm.
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle.
Overall Number of Participants Analyzed 376 384
Median (95% Confidence Interval)
Unit of Measure: months
Unmethylated MGMT Number Analyzed 254 participants 262 participants
14.6
(13.2 to 16.5)
13.3
(12.3 to 14.3)
Methylated MGMT Number Analyzed 122 participants 122 participants
21.4
(17.6 to 29.0)
20.2
(15.4 to 25.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments Unmethylated MGMT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.44
Comments One-sided significance level = 0.05
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.82 to 1.19
Estimation Comments Reference level = Conventional adjuvant TMZ
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments Methylated MGMT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.86
Comments One-sided significance level = 0.05
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.19
Confidence Interval (2-Sided) 95%
0.87 to 1.62
Estimation Comments Reference level = Conventional adjuvant TMZ
4.Secondary Outcome
Title Median Progression-free Survival Time by MGMT Status
Hide Description Progression is defined as greater than 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period. Progression-free survival time is defined as time from registration to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. A concomitant decrease in steroid dose will rule out a progression designation during the first 2 months after completion of radiation therapy. Tumor tissue submitted at baseline was analyzed to determine MGMT (O[6]-methylguanine-DNA methyltransferase) promoter methylation status (methylated / unmethylated). Analysis occurred after 647 deaths were reported.
Time Frame From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
MGMT status was not available for all randomized eligible participants. Therefore, data was only available from 376/411 on the conventional arm and 384/420 on the dose-dense arm.
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle.
Overall Number of Participants Analyzed 376 384
Median (95% Confidence Interval)
Unit of Measure: months
Unmethylated MGMT Number Analyzed 254 participants 262 participants
5.1
(4.3 to 5.7)
6.0
(5.5 to 6.5)
Methylated MGMT Number Analyzed 122 participants 122 participants
6.5
(4.1 to 9.6)
10.1
(7.9 to 12.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments Unmethylated MGMT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments One-sided significance level = 0.05
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.73 to 1.05
Estimation Comments Reference level = Conventional adjuvant TMZ
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments Methylated MGMT
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments One-sided significance level = 0.05
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.66 to 1.15
Estimation Comments Reference level = Conventional adjuvant TMZ
5.Secondary Outcome
Title Best Treatment Response by MGMT Status
Hide Description Response assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1.0): Complete Response (CR), imaging no longer shows enhancing tumor, confirmed by a second scan ≥ 4 weeks later; Partial Response (PR), >=50% decrease in tumor area (two diameters) with patient off all steroids, or on adrenal maintenance only; Minor Response (MR), < 50% decrease in tumor area with patient off all steroids, or on adrenal maintenance only; Stable Disease (SD): scan shows no change with patient receiving stable/decreasing doses of steroids; Progression (P): > 25% increase in tumor area with no decrease in steroid dose since last evaluation. Tumor tissue submitted at baseline was analyzed to determine MGMT (O[6]-methylguanine-DNA methyltransferase) promoter methylation status (methylated / unmethylated). Analysis occurred after 647 deaths were reported.
Time Frame From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Per the protocol, both arms are combined to compare between MGMT status. MGMT status and treatment response was not available for all randomized eligible participants. Therefore, data was only available for 748/831 randomized eligible patients (arms combined).
Arm/Group Title Methylated Unmethylated
Hide Arm/Group Description:
Methylated MGMT (O[6]-methylguanine-DNA methyltransferase)
Unmethylated MGMT (O[6]-methylguanine-DNA methyltransferase)
Overall Number of Participants Analyzed 240 508
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
47
  19.6%
67
  13.2%
Partial Response
34
  14.2%
66
  13.0%
Minor Response
31
  12.9%
55
  10.8%
Stable Response
110
  45.8%
243
  47.8%
Progressive Disease
18
   7.5%
77
  15.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methylated, Unmethylated
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments Two-sided significance level of 0.05
Method Chi-squared
Comments [Not Specified]
6.Secondary Outcome
Title Distribution of Highest Grade AE Reported as Possibly/Probably/Definitely Related to Protocol Treatment
Hide Description Highest grade adverse event (AE) per subject was counted. 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. Analysis occurred after 647 deaths were reported.
Time Frame From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized eligible patients with any adverse events reported as possibly/probably/definitely related to protocol treatment
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle.
Overall Number of Participants Analyzed 351 369
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 0,1,2
231
  65.8%
175
  47.4%
Grade 3,4,5
120
  34.2%
194
  52.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments Two-sided significance level of 0.05
7.Secondary Outcome
Title Overall Survival Status by Progression Status at 6 Months
Hide Description Overall survival time is defined as time from registration to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. Progression is defined as greater than 25% increase in tumor area (two diameters) provided that the patient has not had his/her dose of steroids decreased since the last evaluation period.
Time Frame From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Per the protocol, both arms are combined to compare between 6-month progression status. Eligible pre-randomization participants with any follow-up data.
Arm/Group Title No Progression at 6 Months Progression at 6 Months
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 676 444
Median (95% Confidence Interval)
Unit of Measure: months
20.7
(19.5 to 22.2)
10.1
(8.8 to 10.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection No Progression at 6 Months, Progression at 6 Months
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Two-sided test
Method Log Rank
Comments [Not Specified]
8.Secondary Outcome
Title Mean MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy
Hide Description The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed.
Time Frame Baseline and cycle 10 (approximately 46 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Cycle 10 questionnaires were not completed by all quality of life (QOL) population participants progression-free at 6 months. Therefore, only 24/96 on the conventional arm and 20/95 on the dose-dense arm had data.
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 24 20
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
1.17
(0.72 to 1.61)
1.18
(0.68 to 1.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.96
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
9.Secondary Outcome
Title Mean Neurocognitive Function (NCF) Composite Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy
Hide Description The NCF Composite score is the arithmetic mean of the Hopkins Verbal Learning Test - Revised (HVLT-R) (Free Recall, Delayed Recall, Delayed Recognition), Trail Making Test Part A (TMTA), Trail Making Test Part B (TMTB), and Controlled Oral Word Association (COWA) test 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.
Time Frame Baseline and cycle 10 (approximately 46 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Cycle 10 questionnaires were not completed by all QOL population participants progression-free at 6 months. Therefore, only 17/96 on the conventional arm and 20/95 on the dose-dense arm had data.
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 17 20
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-0.95
(-2.12 to 0.21)
-1.19
(-2.03 to -0.33)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.73
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
10.Secondary Outcome
Title Mean EORTC QLQ-C30 Global Health Status Score at Cycle 10 for Participants Without Progression After 6 Months of Adjuvant Therapy
Hide Description Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best).
Time Frame Baseline and cycle 10 (approximately 46 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Cycle 10 questionnaires were not completed by all QOL population participants progression-free at 6 months. Therefore, only 24/96 on the conventional arm and 22/95 on the dose-dense arm had data.
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 24 22
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
73.3
(64.6 to 81.9)
69.7
(60.1 to 79.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
11.Secondary Outcome
Title Mean Change From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Mid-cyle for Cycle 1
Hide Description The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline.
Time Frame Baseline and mid-cycle 1 (approximately 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Questionnaires were not completed by all QOL population participants. Therefore, only 41/96 on the conventional arm and 35/95 on the dose-dense arm have both baseline and mid-cycle 1 data.
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 41 35
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
0.48
(0.06 to 0.90)
0.39
(-0.08 to 0.87)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
12.Secondary Outcome
Title Mean Change From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Mid-cyle for Cycle 4
Hide Description The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration. Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline.
Time Frame Baseline and mid-cycle 4 (approximately 24 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Questionnaires were not completed by all QOL population participants. Therefore, only 32/96 on the conventional arm and 24/95 on the dose-dense arm have both baseline and mid-cycle 4 data.
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 32 24
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-0.23
(-0.69 to 0.23)
0.19
(-0.40 to 0.77)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.24
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
13.Secondary Outcome
Title Mean Change From Baseline in EORTC QLQ-C30 Global Health Status Score at Mid-cyle for Cycle 1
Hide Description Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline.
Time Frame Baseline and mid-cycle 1 (approximately 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Questionnaires were not completed by all QOL population participants. Therefore, only 40/96 on the conventional arm and 38/95 on the dose-dense arm have both baseline and mid-cycle 1 data.
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 40 38
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-4.58
(-12.63 to 3.47)
-2.63
(-11.37 to 6.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.74
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
14.Secondary Outcome
Title Mean Change From Baseline in EORTC QLQ-C30 Global Health Status Score at Mid-cyle for Cycle 4
Hide Description Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change is calculated as time point - baseline such that a positive change value indicates worse symptoms compared to baseline.
Time Frame Baseline and mid-cycle 4 (approximately 24 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Questionnaires were not completed by all QOL population participants. Therefore, only 30/96 on the conventional arm and 23/95 on the dose-dense arm have both baseline and mid-cycle 4 data.
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 30 23
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-2.78
(-13.87 to 8.32)
-0.72
(-11.91 to 10.46)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.79
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline in Mean EORTC QLQ-C30 Global Health Status
Hide Description Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Change from baseline was calculated as time point value - baseline value with a positive change value indicating improved QOL from baseline.
Time Frame Baseline, 10,12, 22, 24, and 46 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Questionnaires were not completed by all QOL population participants. Therefore, the number of participants reported below are the number with the relevant questions answered at baseline and the given time point on each arm.
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 96 95
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
Week 10 (Cycle 1) Number Analyzed 70 participants 72 participants
0.0
(-6.1 to 6.1)
-2.9
(-8.7 to 2.9)
Week 12 (Cycle 1.5) Number Analyzed 40 participants 38 participants
-4.6
(-12.6 to 3.5)
-2.7
(-11.3 to 6.1)
Week 22 (Cycle 4) Number Analyzed 48 participants 38 participants
3.9
(-2.5 to 10.4)
-4.4
(-12.1 to 3.3)
Week 24 (Cycle 4.5) Number Analyzed 30 participants 23 participants
-2.8
(-13.9 to 8.3)
-0.7
(-11.9 to 10.5)
Week 46 (Cycle 10) Number Analyzed 23 participants 22 participants
5.4
(-7.5 to 18.3)
-1.9
(-9.8 to 6.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments A mixed effects model was run with EORTC QLQ-C30 Global Health Status Score (baseline, 10,12, 22, 24, and 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. Treatment arm is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2184
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept effects are not shown.)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments A mixed effects model was run with EORTC QLQ-C30 Global Health Status Score (baseline, 10,12, 22, 24, and 46 weeks) as the outcome of interest. Treatment arm, RPA class, MGMT status, and time were included in the model. RPA class is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0763
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept effects are not shown.)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments A mixed effects model was run with EORTC QLQ-C30 Global Health Status Score (baseline, 10,12, 22, 24, and 46 weeks) as the outcome of interest. Treatment arm, RPA class, MGMT status, and time were included in the model. MGMT status is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5235
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept effects are not shown.)
16.Secondary Outcome
Title Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score at Cycle 4
Hide Description The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.
Time Frame baseline and cycle 4 (approximately 22 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Questionnaires were not completed by all QOL population participants. Therefore, only 51/96 on the conventional arm and 40/95 on the dose-dense arm have both baseline and cycle 4 data
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 51 40
Measure Type: Count of Participants
Unit of Measure: Participants
5
   9.8%
11
  27.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Z-test of two proportions
Comments [Not Specified]
17.Secondary Outcome
Title Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Interference Score at Cycle 4
Hide Description The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (did not interfere) to 10 (interfered completely). The symptom interference score is the average of the symptom interference items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.
Time Frame baseline and cycle 4 (approximately 22 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Questionnaires were not completed by all QOL population participants. Therefore, only 51/96 on the conventional arm and 40/95 on the dose-dense arm have both baseline and cycle 4 data
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 51 40
Measure Type: Count of Participants
Unit of Measure: Participants
7
  13.7%
13
  32.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Z-test of two proportions
Comments [Not Specified]
18.Secondary Outcome
Title Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 1
Hide Description
  • The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.
  • Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 (very poor) to 7 (excellent) such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). A score worse than baseline by at least 10 is considered deterioration.
  • The 2x2 frequency table of SS deterioration vs. GHS deterioration is presented as four rows.
Time Frame baseline and cycle 1 (approximately 10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Per the protocol, both arms are combined. Questionnaires were not completed by all QOL population participants. Therefore, only 136/191 have both MDASI-BT and EORTC QLQ-C30 at baseline and cycle 1.
Arm/Group Title Both Arms Combined
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 136
Measure Type: Count of Participants
Unit of Measure: Participants
Symptom Severity and GHS deterioration
18
  13.2%
Symptom Severity deterioration only
9
   6.6%
GHS deterioratoin only
31
  22.8%
No deterioration
78
  57.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Both Arms Combined
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Chi-squared
Comments Two-sided test
19.Secondary Outcome
Title Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 4
Hide Description
  • The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.
  • Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 (very poor) to 7 (excellent) such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). A score worse than baseline by at least 10 is considered deterioration.
  • The 2x2 frequency table of SS deterioration vs. GHS deterioration is presented as four rows.
Time Frame baseline and cycle 4 (approximately 22 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Both arms are combined per the protocol. Questionnaires were not completed by all QOL population participants. Therefore, only 86/191 have both MDASI-BT and EORTC QLQ-C30 at baseline and cycle 4.
Arm/Group Title Both Arms Combined
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 86
Measure Type: Count of Participants
Unit of Measure: Participants
Symptom Severity and GHS deterioration
10
  11.6%
Symptom Severity deterioration only
5
   5.8%
GHS deterioration Only
18
  20.9%
No deterioration
53
  61.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Both Arms Combined
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Fisher Exact
Comments Two-sided test
20.Secondary Outcome
Title Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score and EORTC QLQ-C30 Global Health Status Score (GHS) at Cycle 10
Hide Description
  • The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.
  • Global Health Status is calculated from two questions on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30. The question responses range from 1 (very poor) to 7 (excellent) such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). A score worse than baseline by at least 10 is considered deterioration.
  • The 2x2 frequency table of SS deterioration vs. GHS deterioration is presented as four rows.
Time Frame baseline and cycle 10 (approximately 46 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Both arms are combined per the protocol. Questionnaires were not completed by all QOL population participants. Therefore, only 44/191 have both MDASI-BT and EORTC QLQ-C30 at baseline and cycle 10.
Arm/Group Title Both Arms Combined
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 44
Measure Type: Count of Participants
Unit of Measure: Participants
Symptom Severity and GHS deterioration
5
  11.4%
Symptom Severity deterioration only
4
   9.1%
GHS deterioration only
5
  11.4%
No deterioration
30
  68.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Both Arms Combined
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments [Not Specified]
Method Fisher Exact
Comments Two-sided test
21.Secondary Outcome
Title Mean MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score Over Time
Hide Description The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). The symptom severity score is the average of the symptom severity items, given a specified minimum numbers were completed.
Time Frame Baseline, 10, 12, 22, 24, and 46 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Questionnaires were not completed by all QOL population participants. Therefore, the number of participants reported below are the number with the relevant questions answered at baseline and the given time point on each arm.
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 95 96
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
Baseline Number Analyzed 88 participants 86 participants
1.3
(1.0 to 1.5)
1.1
(0.8 to 1.4)
Week 10 (Cycle 1) Number Analyzed 73 participants 74 participants
1.4
(1.1 to 1.7)
1.4
(1.1 to 1.6)
Week 12 (Cycle 1.5) Number Analyzed 41 participants 37 participants
1.6
(1.2 to 2.1)
1.5
(1.1 to 1.8)
Week 22 (Cycle 4) Number Analyzed 51 participants 40 participants
1.0
(0.7 to 1.3)
1.2
(0.9 to 1.5)
Week 24 (Cycle 4.5) Number Analyzed 32 participants 24 participants
1.0
(0.7 to 1.3)
1.1
(0.7 to 1.6)
Week 46 (Cycle 10) Number Analyzed 24 participants 22 participants
1.2
(0.7 to 1.6)
1.1
(0.7 to 1.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments A mixed effects model was run with MDASI Symptom Severity Score (baseline, 10, 12, 22, 24, 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. Treatment arm is reported here.
Type of Statistical Test Superiority
Comments Each explanatory variable is reported separately. (Time and intercept effects are not shown.)
Statistical Test of Hypothesis P-Value 0.1702
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments A mixed effects model was run with EORTC QLQ-C30 Global Health Status Score (baseline, 10, 12, 22, 24, 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. RPA is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8159
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept effects are not shown.)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments A mixed effects model was run with EORTC QLQ-C30 Global Health Status Score (baseline, 10, 12, 22, 24, 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. MGMT status is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2174
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept effects are not shown.)
22.Secondary Outcome
Title Determination of Impactful Baseline Instruments on Overall Survival
Hide Description Overall survival time is defined as time from registration/randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30 subscales are calculated as the mean of component items, then standardized such that subscale scores range from 0 to 100. A high score for a functional scale represents a healthy level of functioning. Controlled Oral Word Association (COWA) score is the sum of correct responses with a range of 0 to infinity. A higher score indicates better functioning. Hopkins Verbal Learning Test - Revised (HVLT-R) score ranges from 0 to 36 for total recall is 0 to 36, 0 to 12 for delayed recall, and -12 to 12 for recognition. A higher score indicates better functioning.
Time Frame From randomization to last follow-up. Maximum follow-up at time of analysis was 4.4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Both arms are combined per the protocol. Questionnaires/assessments were not completed by all QOL population participants. Therefore, only 154/191 have COWA, EORTC QLQ-C30, and HVLT-R baseline assessments (final model covariates)
Arm/Group Title Both Arms Combined
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 154
Median (95% Confidence Interval)
Unit of Measure: months
17.5
(14.0 to 20.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Both Arms Combined
Comments A Cox proportional hazards model was run with overall survival as the outcome of interest and baseline scores as continuous covariates. The final model was determined from stepwise selection. EORTC physical functioning, EORTC role functioning, standardized HVLT-R recognition, standardized HVLT-R recall, and standardized COWA were included in the initial model. EORTC physical functioning is reported here.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Both Arms Combined
Comments A Cox proportional hazards model was run with overall survival as the outcome of interest and baseline scores as continuous covariates. The final model was determined from stepwise selection. EORTC physical functioning, EORTC role functioning, standardized HVLT-R recognition, standardized HVLT-R recall, and standardized COWA were included in the initial model. Standardized HVLT-R recognition is reported here.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.043
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Both Arms Combined
Comments A Cox proportional hazards model was run with overall survival as the outcome of interest and baseline scores as continuous covariates. The final model was determined from stepwise selection. EORTC physical functioning, EORTC role functioning, standardized HVLT-R recognition, standardized HVLT-R recall, and standardized COWA were included in the initial model. Standardized COWA is reported here.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
23.Secondary Outcome
Title Mean Neurocognitive Function (NCF) Composite Score Over Time
Hide Description The NCF 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.
Time Frame Baseline, 10, 22, and 46 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Questionnaires were not completed by all QOL population participants. Therefore, the number of participants reported below are the number with data at baseline and the given time point on each arm.
Arm/Group Title Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle for 6 cycles, up to 12 cycles.
Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 96 95
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
Baseline Number Analyzed 80 participants 85 participants
-1.2
(-1.6 to -0.9)
-1.5
(-1.8 to -1.1)
Week 10 (Cycle 1) Number Analyzed 67 participants 63 participants
-1.3
(-1.7 to -1.0)
-1.45
(-1.9 to -1.0)
Week 22 (Cycle 4) Number Analyzed 39 participants 35 participants
-1.1
(-1.6 to -0.6)
-1.3
(-2.0 to -0.6)
Week 46 (Cycle 10) Number Analyzed 17 participants 20 participants
-1.0
(-2.1 to 0.2)
-1.2
(-2.0 to -0.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments A mixed effects model was run with NCF Composite Score (baseline, 10, 22, 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. Treatment arm is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2357
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept effects are not shown.)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments A mixed effects model was run with NCF Composite Score (baseline, 10, 22, 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. RPA is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0147
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept effects are not shown.)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Conventional Adjuvant TMZ, Dose-dense Adjuvant TMZ
Comments A mixed effects model was run with NCF Composite Score (baseline, 10, 22, 46 weeks) as the outcome of interest. Treatment arm, recursive partitioning analysis (RPA) class, MGMT status, and time were included in the model. MGMT Status is reported here.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.457
Comments [Not Specified]
Method Mixed Models Analysis
Comments Each explanatory variable is reported separately. (Time and intercept effects are not shown.)
24.Secondary Outcome
Title Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition Score at Cycle 1
Hide Description
  • The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.
  • The HVLT-R Delayed Recognition raw score is the number of of correctly identified words minus the number of incorrectly identified words from a list of words including 12 nouns memorized 20 minutes prior. The raw score ranges from -12 to 12. with a higher score indicates better functioning. Scores are standardized (mean 0, standard deviation 1), adjusting for age,education, and gender as necessary. A score worse than baseline by at least two is considered deterioration.
  • The 2x2 frequency table of SS deterioration vs. HVLT-R deterioration is presented as four rows.
Time Frame baseline and cycle 1 (approximately 10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Both arms are combined per the protocol. Questionnaires/assessments were not completed by all QOL population participants. Therefore, only 116/191 have both MDASI-BT and HVLT-R at baseline and cycle 1.
Arm/Group Title Both Arms Combined
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 116
Measure Type: Count of Participants
Unit of Measure: Participants
Cognitive and HVLT-R deterioration
10
   8.6%
Cognitive deterioration only
12
  10.3%
HVLT-R deterioration only
20
  17.2%
No deterioration
74
  63.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Both Arms Combined
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Chi-squared
Comments Two-sided test
25.Secondary Outcome
Title Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition (DR) Score at Cycle 4
Hide Description
  • The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.
  • The HVLT-R Delayed Recognition raw score is the number of of correctly identified words minus the number of incorrectly identified words from a list of words including 12 nouns memorized 20 minutes prior. The raw score ranges from -12 to 12. with a higher score indicates better functioning. Scores are standardized (mean 0, standard deviation 1), adjusting for age,education, and gender as necessary. A score worse than baseline by at least two is considered deterioration.
  • The 2x2 frequency table of SS deterioration vs. HVLT-R deterioration is presented as four rows.
Time Frame baseline and cycle 4 (approximately 22 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Both arms are combined per the protocol. Questionnaires/assessments were not completed by all QOL population participants. Therefore, only 71/191 have both MDASI-BT and HVLT-R at baseline and cycle 4.
Arm/Group Title Both Arms Combined
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 71
Measure Type: Count of Participants
Unit of Measure: Participants
Cognitive and Delayed Recognition deterioration
3
   4.2%
Cognitive deterioration only
9
  12.7%
Delayed Recognition deterioration only
14
  19.7%
No deterioration
45
  63.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Both Arms Combined
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99
Comments [Not Specified]
Method Fisher Exact
Comments Two-sided test
26.Secondary Outcome
Title Number of Participants With Deterioration From Baseline in MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) Cognitive Score and Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recognition (DR) Score at Cycle 10
Hide Description
  • The MDASI-BT is a 28-item patient-reported outcome measure assessing symptom severity (SS) and resulting interference with daily living in brain cancer patients. All items range from 0 (not present) to 10 (as bad as you can imagine). A SS score is the average of the SS items, given a specified minimum numbers were completed. A score worse than baseline by at least one is considered deterioration.
  • The HVLT-R Delayed Recognition raw score is the number of of correctly identified words minus the number of incorrectly identified words from a list of words including 12 nouns memorized 20 minutes prior. The raw score ranges from -12 to 12. with a higher score indicates better functioning. Scores are standardized (mean 0, standard deviation 1), adjusting for age,education, and gender as necessary. A score worse than baseline by at least two is considered deterioration.
  • The 2x2 frequency table of SS deterioration vs. HVLT-R deterioration is presented as four rows.
Time Frame baseline and cycle 10 (approximately 46 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Both arms are combined per the protocol. Questionnaires/assessments were not completed by all QOL population participants. Therefore, only 36/191 have both MDASI-BT and HVLT-R at baseline and cycle 10.
Arm/Group Title Both Arms Combined
Hide Arm/Group Description:
Concurrent radiation therapy with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, either [100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle] or [75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle] for 6 cycles, up to 12 cycles.
Overall Number of Participants Analyzed 36
Measure Type: Count of Participants
Unit of Measure: Participants
Cognitive and Delayed Recognition deterioration
3
   8.3%
Cognitive deterioration only
6
  16.7%
Delayed Recognition deterioration only
4
  11.1%
No deterioration
23
  63.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Both Arms Combined
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments [Not Specified]
Method Fisher Exact
Comments Two-sided test
Time Frame [Not Specified]
Adverse Event Reporting Description Eligible participants with adverse event data: concurrent RT and TMZ only arm (not randomized): 285/292; conventional adjuvant TMZ arm: 409/411; dose-dense adjuvant TMZ arm: 420/422.
 
Arm/Group Title No Adjuvant TMZ (Not Randomized) Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Hide Arm/Group Description Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Not randomized to either adjuvant TMZ arm. Concurrent radiation therapy with concurrent temozolomide (TMZ) (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 100mg/m2 adjuvant temozolomide days 1 to 5 of 28 day cycle. Concurrent radiation therapy (RT) with concurrent temozolomide (75 mg/m2) up to 49 doses. Starting four weeks after completion of RT, 75mg/m2 adjuvant temozolomide days 1-21 of 28 day cycle.
All-Cause Mortality
No Adjuvant TMZ (Not Randomized) Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
No Adjuvant TMZ (Not Randomized) Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   105/285 (36.84%)   131/409 (32.03%)   142/420 (33.81%) 
Blood and lymphatic system disorders       
Blood/bone marrow - Other: * 1  0/285 (0.00%)  2/409 (0.49%)  1/420 (0.24%) 
Bone marrow depression NOS * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Febrile neutropenia * 1  2/285 (0.70%)  2/409 (0.49%)  1/420 (0.24%) 
Haemolysis NOS * 1  1/285 (0.35%)  0/409 (0.00%)  1/420 (0.24%) 
Hemoglobin * 1  12/285 (4.21%)  6/409 (1.47%)  5/420 (1.19%) 
Thrombotic microangiopathy NOS * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Cardiac disorders       
Atrial fibrillation * 1  1/285 (0.35%)  3/409 (0.73%)  2/420 (0.48%) 
Atrial flutter * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Atrial tachycardia * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Cardiac General - Other: * 1  2/285 (0.70%)  0/409 (0.00%)  0/420 (0.00%) 
Myocardial ischaemia * 1  1/285 (0.35%)  1/409 (0.24%)  0/420 (0.00%) 
Pericardial effusion * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Sinus bradycardia * 1  0/285 (0.00%)  1/409 (0.24%)  1/420 (0.24%) 
Sinus tachycardia * 1  1/285 (0.35%)  0/409 (0.00%)  2/420 (0.48%) 
Supraventricular extrasystoles * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Endocrine disorders       
Cushingoid * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Hypothyroidism * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Eye disorders       
Diplopia * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Extraocular muscle disorder * 1  0/285 (0.00%)  2/409 (0.49%)  0/420 (0.00%) 
Ocular/visual - Other: * 1  0/285 (0.00%)  2/409 (0.49%)  0/420 (0.00%) 
Photopsia * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Retinal detachment * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Vision blurred * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Gastrointestinal disorders       
Abdominal pain NOS * 1  0/285 (0.00%)  3/409 (0.73%)  2/420 (0.48%) 
Colitis NOS * 1  2/285 (0.70%)  1/409 (0.24%)  0/420 (0.00%) 
Colonic perforation * 1  1/285 (0.35%)  0/409 (0.00%)  2/420 (0.48%) 
Constipation * 1  0/285 (0.00%)  4/409 (0.98%)  0/420 (0.00%) 
Diarrhoea NOS * 1  1/285 (0.35%)  2/409 (0.49%)  3/420 (0.71%) 
Dysphagia * 1  2/285 (0.70%)  0/409 (0.00%)  1/420 (0.24%) 
Enteritis * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Gastritis NOS * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Gastrointestinal - Other: * 1  1/285 (0.35%)  2/409 (0.49%)  1/420 (0.24%) 
Nausea * 1  6/285 (2.11%)  7/409 (1.71%)  11/420 (2.62%) 
Oseophagitis NOS * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Pancreatitis NOS * 1  0/285 (0.00%)  1/409 (0.24%)  1/420 (0.24%) 
Rectal hemorrhage * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Small intestinal stricture NOS * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Vomiting NOS * 1  5/285 (1.75%)  5/409 (1.22%)  9/420 (2.14%) 
General disorders       
Chest pain * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Constitutional Symptoms - Other: * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Death NOS * 1  2/285 (0.70%)  1/409 (0.24%)  0/420 (0.00%) 
Disease progression NOS * 1  6/285 (2.11%)  3/409 (0.73%)  2/420 (0.48%) 
Edema: head and neck: * 1  0/285 (0.00%)  0/409 (0.00%)  2/420 (0.48%) 
Edema: limb: * 1  2/285 (0.70%)  2/409 (0.49%)  0/420 (0.00%) 
Fatigue * 1  9/285 (3.16%)  9/409 (2.20%)  11/420 (2.62%) 
Gait abnormal NOS * 1  2/285 (0.70%)  1/409 (0.24%)  0/420 (0.00%) 
Influenza-like illness * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Multi-organ failure * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Pain - Other: * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Pain NOS * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Pyrexia * 1  6/285 (2.11%)  5/409 (1.22%)  7/420 (1.67%) 
Rigors * 1  1/285 (0.35%)  1/409 (0.24%)  0/420 (0.00%) 
Sudden death * 1  2/285 (0.70%)  0/409 (0.00%)  1/420 (0.24%) 
Hepatobiliary disorders       
Cholecystitis NOS * 1  0/285 (0.00%)  1/409 (0.24%)  1/420 (0.24%) 
Hepatic failure * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Immune system disorders       
Allergy/immunology - Other: * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Cytokine release syndrome * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Hypersensitivity NOS * 1  3/285 (1.05%)  0/409 (0.00%)  3/420 (0.71%) 
Infections and infestations       
Abdominal infection * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Arthritis infective NOS * 1  0/285 (0.00%)  1/409 (0.24%)  1/420 (0.24%) 
Bladder infection NOS * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Bone infection NOS * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Bronchitis NOS * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Encephalitis NOS * 1  1/285 (0.35%)  0/409 (0.00%)  1/420 (0.24%) 
Eye infection NOS * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Infection - Other: * 1  3/285 (1.05%)  4/409 (0.98%)  2/420 (0.48%) 
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Biliary tree * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Bladder (urinary) * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Bronchus * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Kidney * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Lung (pneumonia) * 1  1/285 (0.35%)  2/409 (0.49%)  4/420 (0.95%) 
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Meninges (meningitis) * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Rectum * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Soft tissue NOS * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Infection with normal ANC or Grade 1 or 2 neutrophils: Blood * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Infection with normal ANC or Grade 1 or 2 neutrophils: Esophagus * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Infection with normal ANC or Grade 1 or 2 neutrophils: Nerve-peripheral * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Infection with normal ANC or Grade 1 or 2 neutrophils: Wound * 1  2/285 (0.70%)  2/409 (0.49%)  0/420 (0.00%) 
Infection with unknown ANC: Lung (pneumonia) * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Infection with unknown ANC: Meninges (meningitis) * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Infection with unknown ANC: Skin (cellulitis) * 1  1/285 (0.35%)  1/409 (0.24%)  0/420 (0.00%) 
Infectous meningitis * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Opportunisitic infection * 1  1/285 (0.35%)  0/409 (0.00%)  5/420 (1.19%) 
Pneumonia NOS * 1  0/285 (0.00%)  4/409 (0.98%)  3/420 (0.71%) 
Respiratory tract infection NOS * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Rhinitis infective * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Sepsis NOS * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Sinusitis NOS * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Skin infection * 1  1/285 (0.35%)  5/409 (1.22%)  1/420 (0.24%) 
Urinary tract infection NOS * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Wound infection * 1  0/285 (0.00%)  0/409 (0.00%)  2/420 (0.48%) 
Injury, poisoning and procedural complications       
Fracture NOS * 1  2/285 (0.70%)  1/409 (0.24%)  3/420 (0.71%) 
Vascular access NOS complication * 1  2/285 (0.70%)  3/409 (0.73%)  1/420 (0.24%) 
Investigations       
Alanine aminotransferase increased * 1  5/285 (1.75%)  3/409 (0.73%)  3/420 (0.71%) 
Aspartate aminotransferase increased * 1  4/285 (1.40%)  3/409 (0.73%)  2/420 (0.48%) 
Blood alkaline phosphatase increased * 1  2/285 (0.70%)  3/409 (0.73%)  3/420 (0.71%) 
Blood amylase increased * 1  0/285 (0.00%)  1/409 (0.24%)  1/420 (0.24%) 
Blood bilirubin increased * 1  4/285 (1.40%)  3/409 (0.73%)  2/420 (0.48%) 
Blood creatinine increased * 1  2/285 (0.70%)  0/409 (0.00%)  2/420 (0.48%) 
CD4 lymphocytes decreased * 1  0/285 (0.00%)  0/409 (0.00%)  6/420 (1.43%) 
Gamma-glutamyltransferase increased * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Inappropriate antidiuretic hormone secretion * 1  1/285 (0.35%)  1/409 (0.24%)  0/420 (0.00%) 
Leukopenia NOS * 1  17/285 (5.96%)  15/409 (3.67%)  14/420 (3.33%) 
Lipase increased * 1  0/285 (0.00%)  1/409 (0.24%)  1/420 (0.24%) 
Lymphopenia * 1  11/285 (3.86%)  5/409 (1.22%)  23/420 (5.48%) 
Metabolic/laboratory - Other: * 1  1/285 (0.35%)  3/409 (0.73%)  1/420 (0.24%) 
Neutrophil count * 1  20/285 (7.02%)  15/409 (3.67%)  11/420 (2.62%) 
Platelet count decreased * 1  34/285 (11.93%)  20/409 (4.89%)  16/420 (3.81%) 
Prothrombin time prolonged * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Troponin I increased * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Weight decreased * 1  1/285 (0.35%)  1/409 (0.24%)  1/420 (0.24%) 
Metabolism and nutrition disorders       
Acidosis NOS * 1  0/285 (0.00%)  1/409 (0.24%)  1/420 (0.24%) 
Alkalosis NOS * 1  1/285 (0.35%)  1/409 (0.24%)  0/420 (0.00%) 
Anorexia * 1  2/285 (0.70%)  2/409 (0.49%)  5/420 (1.19%) 
Blood bicarbonate decreased * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Dehydration * 1  5/285 (1.75%)  3/409 (0.73%)  7/420 (1.67%) 
Hyperglycaemia NOS * 1  0/285 (0.00%)  6/409 (1.47%)  2/420 (0.48%) 
Hyperkalaemia * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Hypoalbuminemia * 1  3/285 (1.05%)  2/409 (0.49%)  4/420 (0.95%) 
Hypocalcemia * 1  2/285 (0.70%)  0/409 (0.00%)  0/420 (0.00%) 
Hypoglycemia NOS * 1  0/285 (0.00%)  1/409 (0.24%)  1/420 (0.24%) 
Hypokalemia * 1  3/285 (1.05%)  4/409 (0.98%)  6/420 (1.43%) 
Hypomagnesemia * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Hyponatremia * 1  5/285 (1.75%)  6/409 (1.47%)  1/420 (0.24%) 
Musculoskeletal and connective tissue disorders       
Back pain * 1  0/285 (0.00%)  2/409 (0.49%)  1/420 (0.24%) 
Chest wall pain * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Muscle weakness NOS * 1  2/285 (0.70%)  2/409 (0.49%)  10/420 (2.38%) 
Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-lower * 1  0/285 (0.00%)  2/409 (0.49%)  1/420 (0.24%) 
Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-upper * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Muscle weakness, generalized or specific area (not due to neuropathy): Left-sided * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Muscle weakness, generalized or specific area (not due to neuropathy): Right-sided * 1  0/285 (0.00%)  1/409 (0.24%)  2/420 (0.48%) 
Musculoskeletal/soft tissue - Other: * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Neck pain * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Pain in extremity * 1  1/285 (0.35%)  2/409 (0.49%)  3/420 (0.71%) 
Nervous system disorders       
Ataxia * 1  0/285 (0.00%)  0/409 (0.00%)  4/420 (0.95%) 
CNS necrosis/cystic progression: * 1  0/285 (0.00%)  2/409 (0.49%)  1/420 (0.24%) 
Cerebral ischaemia * 1  3/285 (1.05%)  3/409 (0.73%)  4/420 (0.95%) 
Cerebrospinal fluid leak * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Cognitive disorder * 1  0/285 (0.00%)  1/409 (0.24%)  5/420 (1.19%) 
Convulsions NOS * 1  9/285 (3.16%)  23/409 (5.62%)  24/420 (5.71%) 
Depressed level of consciousness * 1  2/285 (0.70%)  2/409 (0.49%)  3/420 (0.71%) 
Diaphragmatic paralysis * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Dizziness * 1  2/285 (0.70%)  5/409 (1.22%)  3/420 (0.71%) 
Dysgeusia * 1  0/285 (0.00%)  2/409 (0.49%)  1/420 (0.24%) 
Encephalopathy * 1  1/285 (0.35%)  1/409 (0.24%)  2/420 (0.48%) 
Extrapyramidal disorder * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Headache * 1  6/285 (2.11%)  9/409 (2.20%)  7/420 (1.67%) 
Hemorrhagic stroke * 1  4/285 (1.40%)  0/409 (0.00%)  0/420 (0.00%) 
Hydrocephalus acquired * 1  0/285 (0.00%)  3/409 (0.73%)  2/420 (0.48%) 
Hyperreflexia * 1  2/285 (0.70%)  1/409 (0.24%)  0/420 (0.00%) 
Memory impairment * 1  1/285 (0.35%)  3/409 (0.73%)  3/420 (0.71%) 
Mental status changes * 1  1/285 (0.35%)  1/409 (0.24%)  1/420 (0.24%) 
Muscle weakness, generalized or specific area (not due to neuropathy): Facial * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Neuralgia NOS * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Neurology - Other: * 1  4/285 (1.40%)  3/409 (0.73%)  4/420 (0.95%) 
Neuropathy: cranial: CN VIII Hearing and balance * 1  1/285 (0.35%)  0/409 (0.00%)  1/420 (0.24%) 
Peripheral motor neuropathy * 1  1/285 (0.35%)  8/409 (1.96%)  7/420 (1.67%) 
Peripheral sensory neuropathy * 1  1/285 (0.35%)  1/409 (0.24%)  2/420 (0.48%) 
Speech disorder * 1  1/285 (0.35%)  3/409 (0.73%)  2/420 (0.48%) 
Syncope * 1  1/285 (0.35%)  1/409 (0.24%)  2/420 (0.48%) 
Syncope vasovagal * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Tremor * 1  0/285 (0.00%)  1/409 (0.24%)  1/420 (0.24%) 
Psychiatric disorders       
Agitation * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Anxiety * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Confusional state * 1  5/285 (1.75%)  12/409 (2.93%)  10/420 (2.38%) 
Depression * 1  1/285 (0.35%)  4/409 (0.98%)  4/420 (0.95%) 
Insomnia * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Libido decreased * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Personality change * 1  0/285 (0.00%)  3/409 (0.73%)  0/420 (0.00%) 
Psychosis aggravated * 1  1/285 (0.35%)  2/409 (0.49%)  0/420 (0.00%) 
Renal and urinary disorders       
Cystitis NOS * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Renal failure NOS * 1  2/285 (0.70%)  0/409 (0.00%)  1/420 (0.24%) 
Urinary incontinence * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Urinary retention * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Reproductive system and breast disorders       
Erectile dysfunction NOS * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Scrotal pain * 1  1/285 (0.35%)  0/409 (0.00%)  0/420 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Aspiration * 1  0/285 (0.00%)  2/409 (0.49%)  1/420 (0.24%) 
Cough * 1  0/285 (0.00%)  0/409 (0.00%)  3/420 (0.71%) 
Dyspnoea * 1  7/285 (2.46%)  5/409 (1.22%)  7/420 (1.67%) 
Hypoxia * 1  3/285 (1.05%)  1/409 (0.24%)  6/420 (1.43%) 
Nasal cavity/paranasal sinus reactions: * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Pleural effusion * 1  3/285 (1.05%)  0/409 (0.00%)  0/420 (0.00%) 
Pneumonitis NOS * 1  7/285 (2.46%)  4/409 (0.98%)  6/420 (1.43%) 
Pulmonary/upper respiratory - Other: * 1  1/285 (0.35%)  0/409 (0.00%)  2/420 (0.48%) 
Respiratory tract hemorrhage NOS * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Skin and subcutaneous tissue disorders       
Acne NOS * 1  1/285 (0.35%)  0/409 (0.00%)  1/420 (0.24%) 
Dermatitis exfoliative NOS * 1  1/285 (0.35%)  1/409 (0.24%)  3/420 (0.71%) 
Pain of skin * 1  0/285 (0.00%)  0/409 (0.00%)  1/420 (0.24%) 
Petechiae * 1  0/285 (0.00%)  1/409 (0.24%)  0/420 (0.00%) 
Vascular disorders       
Hematoma * 1  0/285 (0.00%)  0/409 (0.00%)  2/420 (0.48%) 
Hypotension NOS * 1  3/285 (1.05%)  1/409 (0.24%)  3/420 (0.71%) 
Thrombosis * 1  15/285 (5.26%)  15/409 (3.67%)  19/420 (4.52%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
No Adjuvant TMZ (Not Randomized) Conventional Adjuvant TMZ Dose-dense Adjuvant TMZ
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   216/285 (75.79%)   376/409 (91.93%)   392/420 (93.33%) 
Blood and lymphatic system disorders       
Hemoglobin * 1  69/285 (24.21%)  142/409 (34.72%)  171/420 (40.71%) 
Ear and labyrinth disorders       
Hearing impaired * 1  8/285 (2.81%)  27/409 (6.60%)  20/420 (4.76%) 
Eye disorders       
Ocular/visual - Other: * 1  16/285 (5.61%)  37/409 (9.05%)  27/420 (6.43%) 
Vision blurred * 1  19/285 (6.67%)  48/409 (11.74%)  54/420 (12.86%) 
Gastrointestinal disorders       
Abdominal pain NOS * 1  5/285 (1.75%)  17/409 (4.16%)  25/420 (5.95%) 
Constipation * 1  58/285 (20.35%)  135/409 (33.01%)  129/420 (30.71%) 
Diarrhoea NOS * 1  12/285 (4.21%)  50/409 (12.22%)  75/420 (17.86%) 
Dry mouth * 1  7/285 (2.46%)  22/409 (5.38%)  26/420 (6.19%) 
Dyspepsia * 1  11/285 (3.86%)  30/409 (7.33%)  32/420 (7.62%) 
Nausea * 1  79/285 (27.72%)  226/409 (55.26%)  228/420 (54.29%) 
Stomatitis * 1  9/285 (3.16%)  20/409 (4.89%)  24/420 (5.71%) 
Vomiting NOS * 1  32/285 (11.23%)  114/409 (27.87%)  117/420 (27.86%) 
General disorders       
Edema: head and neck: * 1  7/285 (2.46%)  15/409 (3.67%)  27/420 (6.43%) 
Edema: limb: * 1  18/285 (6.32%)  49/409 (11.98%)  54/420 (12.86%) 
Fatigue * 1  134/285 (47.02%)  292/409 (71.39%)  320/420 (76.19%) 
Pain - Other: * 1  3/285 (1.05%)  29/409 (7.09%)  23/420 (5.48%) 
Pyrexia * 1  8/285 (2.81%)  25/409 (6.11%)  27/420 (6.43%) 
Injury, poisoning and procedural complications       
Dermatitis radiation NOS * 1  43/285 (15.09%)  97/409 (23.72%)  103/420 (24.52%) 
Radiation recall syndrome * 1  10/285 (3.51%)  20/409 (4.89%)  26/420 (6.19%) 
Investigations       
Alanine aminotransferase increased * 1  41/285 (14.39%)  100/409 (24.45%)  109/420 (25.95%) 
Aspartate aminotransferase increased * 1  21/285 (7.37%)  64/409 (15.65%)  70/420 (16.67%) 
Blood alkaline phosphatase increased * 1  17/285 (5.96%)  46/409 (11.25%)  49/420 (11.67%) 
Blood creatinine increased * 1  7/285 (2.46%)  25/409 (6.11%)  32/420 (7.62%) 
CD4 lymphocytes decreased * 1  0/285 (0.00%)  13/409 (3.18%)  32/420 (7.62%) 
Leukopenia NOS * 1  44/285 (15.44%)  152/409 (37.16%)  190/420 (45.24%) 
Lymphopenia * 1  49/285 (17.19%)  170/409 (41.56%)  179/420 (42.62%) 
Metabolic/laboratory - Other: * 1  16/285 (5.61%)  39/409 (9.54%)  38/420 (9.05%) 
Neutrophil count * 1  18/285 (6.32%)  89/409 (21.76%)  107/420 (25.48%) 
Platelet count decreased * 1  53/285 (18.60%)  161/409 (39.36%)  163/420 (38.81%) 
Weight decreased * 1  12/285 (4.21%)  54/409 (13.20%)  73/420 (17.38%) 
Metabolism and nutrition disorders       
Anorexia * 1  48/285 (16.84%)  113/409 (27.63%)  140/420 (33.33%) 
Hyperglycaemia NOS * 1  50/285 (17.54%)  116/409 (28.36%)  130/420 (30.95%) 
Hypernatremia * 1  4/285 (1.40%)  21/409 (5.13%)  20/420 (4.76%) 
Hypoalbuminemia * 1  20/285 (7.02%)  46/409 (11.25%)  56/420 (13.33%) 
Hypocalcemia * 1  20/285 (7.02%)  39/409 (9.54%)  45/420 (10.71%) 
Hypoglycemia NOS * 1  4/285 (1.40%)  21/409 (5.13%)  22/420 (5.24%) 
Hypokalemia * 1  18/285 (6.32%)  46/409 (11.25%)  51/420 (12.14%) 
Hyponatremia * 1  22/285 (7.72%)  48/409 (11.74%)  60/420 (14.29%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  4/285 (1.40%)  27/409 (6.60%)  32/420 (7.62%) 
Back pain * 1  9/285 (3.16%)  23/409 (5.62%)  23/420 (5.48%) 
Muscle weakness NOS * 1  19/285 (6.67%)  41/409 (10.02%)  49/420 (11.67%) 
Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-lower * 1  11/285 (3.86%)  33/409 (8.07%)  26/420 (6.19%) 
Muscle weakness, generalized or specific area (not due to neuropathy): Left-sided * 1  4/285 (1.40%)  24/409 (5.87%)  16/420 (3.81%) 
Myalgia * 1  5/285 (1.75%)  13/409 (3.18%)  24/420 (5.71%) 
Pain in extremity * 1  11/285 (3.86%)  22/409 (5.38%)  30/420 (7.14%) 
Nervous system disorders       
Ataxia * 1  23/285 (8.07%)  56/409 (13.69%)  54/420 (12.86%) 
Cognitive disorder * 1  11/285 (3.86%)  31/409 (7.58%)  37/420 (8.81%) 
Convulsions NOS * 1  34/285 (11.93%)  80/409 (19.56%)  87/420 (20.71%) 
Depressed level of consciousness * 1  8/285 (2.81%)  15/409 (3.67%)  23/420 (5.48%) 
Dizziness * 1  25/285 (8.77%)  93/409 (22.74%)  75/420 (17.86%) 
Dysgeusia * 1  19/285 (6.67%)  43/409 (10.51%)  63/420 (15.00%) 
Headache * 1  69/285 (24.21%)  193/409 (47.19%)  199/420 (47.38%) 
Hyperreflexia * 1  9/285 (3.16%)  24/409 (5.87%)  23/420 (5.48%) 
Memory impairment * 1  29/285 (10.18%)  84/409 (20.54%)  85/420 (20.24%) 
Neurology - Other: * 1  7/285 (2.46%)  34/409 (8.31%)  34/420 (8.10%) 
Peripheral motor neuropathy * 1  33/285 (11.58%)  58/409 (14.18%)  64/420 (15.24%) 
Peripheral sensory neuropathy * 1  20/285 (7.02%)  58/409 (14.18%)  64/420 (15.24%) 
Speech disorder * 1  34/285 (11.93%)  65/409 (15.89%)  64/420 (15.24%) 
Tremor * 1  9/285 (3.16%)  54/409 (13.20%)  44/420 (10.48%) 
Psychiatric disorders       
Agitation * 1  3/285 (1.05%)  27/409 (6.60%)  17/420 (4.05%) 
Anxiety * 1  15/285 (5.26%)  50/409 (12.22%)  41/420 (9.76%) 
Confusional state * 1  32/285 (11.23%)  57/409 (13.94%)  59/420 (14.05%) 
Depression * 1  19/285 (6.67%)  55/409 (13.45%)  62/420 (14.76%) 
Insomnia * 1  39/285 (13.68%)  85/409 (20.78%)  77/420 (18.33%) 
Renal and urinary disorders       
Pollakiuria * 1  5/285 (1.75%)  21/409 (5.13%)  21/420 (5.00%) 
Urinary incontinence * 1  8/285 (2.81%)  14/409 (3.42%)  22/420 (5.24%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  14/285 (4.91%)  49/409 (11.98%)  53/420 (12.62%) 
Dyspnoea * 1  15/285 (5.26%)  35/409 (8.56%)  37/420 (8.81%) 
Skin and subcutaneous tissue disorders       
Alopecia * 1  86/285 (30.18%)  173/409 (42.30%)  191/420 (45.48%) 
Dermatitis exfoliative NOS * 1  13/285 (4.56%)  63/409 (15.40%)  76/420 (18.10%) 
Pruritus * 1  15/285 (5.26%)  45/409 (11.00%)  53/420 (12.62%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Only participants registered after 07-12-2007 were able to participate in the quality of life / patient reported outcome study components.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Wendy Seiferheld
Organization: Radiation Therapy Oncology Group (RTOG)
EMail: wseiferheld@acr.org
Publications of Results:
Aldape KD, Wang M, Sulman EP, et al.: RTOG 0525: molecular correlates from a randomized phase III trial of newly diagnosed glioblastoma. [Abstract] J Clin Oncol 29 (Suppl 15): A-LBA2000, 2011.
Armstrong TS, Wefel JS, Wang M, et al.: Clinical utility of neurocognitive function (NCF), quality of life (QOL), and symptom assessment as prognostic factors for survival and measures of treatment effects on RTOG 0525. [Abstract] J Clin Oncol 29 (Suppl 15): A-2016, 2011.
Wang M, Dignam J, Won M, et al.: Variation over time and interdependence between disease progression and death among patients with glioblastoma (GBM) on RTOG 0525. [Abstract] J Clin Oncol 29 (Suppl 15): A-2017, 2011.
Aldape KD, Jones G, Wang M, et al.: MGMT methylation testing in RTOG 0525: A phase III trial of newly diagnosed glioblastoma. [Abstract] J Clin Oncol 27 (Suppl 15): A-2051, 2009.
Layout table for additonal information
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00304031    
Other Study ID Numbers: RTOG-0525
CDR0000465183
EORTC-26052
EORTC-22053
NCI-2009-00731 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted: March 15, 2006
First Posted: March 17, 2006
Results First Submitted: March 28, 2014
Results First Posted: April 30, 2014
Last Update Posted: June 9, 2020