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Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed Glioblastoma

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: NCT00884741
Recruitment Status : Completed
First Posted : April 21, 2009
Results First Posted : October 12, 2016
Last Update Posted : July 24, 2019
Sponsor:
Collaborators:
Radiation Therapy Oncology Group
NRG Oncology
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Glioblastoma
Gliosarcoma
Supratentorial Glioblastoma
Interventions Radiation: 3-Dimensional Conformal Radiation Therapy
Biological: Bevacizumab
Radiation: Intensity-Modulated Radiation Therapy
Other: Laboratory Biomarker Analysis
Other: Placebo
Other: Quality-of-Life Assessment
Drug: Temozolomide
Enrollment 637
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Step 1 Registration Step 2 Registration: Pre-Randomization TMZ+RT Randomized Arm 1: TMZ+RT + Placebo Randomized Arm 2: TMZ+RT + Bevacizumab
Hide Arm/Group Description No treatment. Central Pathology Tissue Screening to confirm histology and adequacy of tissue for MGMT analysis and molecular profile. Tumor tissue must be received and central review confirmation completed before STEP 2 registration can occur. Temozolomide pre-randomization, radiation therapy pre-randomization Temozolomide post-randomization,Radiation therapy post-randomization, placebo Temozolomide post-randomization, radiation therapy post-randomization, bevacizumab
Period Title: Step 1 Registration: Tissue Screening
Started 978 0 0 0
Completed 666 0 0 0
Not Completed 312 0 0 0
Reason Not Completed
Protocol Violation             157             0             0             0
Death             3             0             0             0
Physician Decision             3             0             0             0
Insufficient tissue             105             0             0             0
Disease progression             12             0             0             0
Patient refusal             32             0             0             0
Period Title: Step 2 Registration: Tissue Analysis
Started 0 [1] 666 [2] 0 0
Completed 0 637 0 0
Not Completed 0 29 0 0
Reason Not Completed
Protocol Violation             0             15             0             0
Death             0             1             0             0
Adverse Event             0             2             0             0
Patient refusal             0             7             0             0
Disease Progression             0             4             0             0
[1]
Step 1 Registration Arm goes to Step 2 Registration Arm
[2]
These patients completed the previous period on the Step 1 Registration arm.
Period Title: Randomization
Started 0 0 [1] 317 [2] 320 [2]
Completed 0 0 309 [3] 312 [3]
Not Completed 0 0 8 8
Reason Not Completed
Protocol Violation             0             0             8             8
[1]
Step 2 Registration Arm goes to a randomized arm.
[2]
These patients completed the previous period on the Step 2 Registration arm.
[3]
Patients with data available for the primary analysis are considered to have completed the study.
Arm/Group Title Pre-Randomization TMZ+RT Randomized Arm 1: TMZ+RT + Placebo Randomized Arm 2: TMZ+RT + Bevacizumab Total
Hide Arm/Group Description Temozolomide pre-randomization, radiation therapy pre-randomization. Note that for the purpose of this table, this arm only includes patients that did not continue to randomization. Temozolomide post-randomization,Radiation therapy post-randomization, placebo Temozolomide post-randomization, radiation therapy post-randomization, bevacizumab Total of all reporting groups
Overall Number of Baseline Participants 29 309 312 650
Hide Baseline Analysis Population Description
All eligible patients. Note that the Pre-Randomization TMZ+RT arm only includes eligible patients that did not continue to randomization.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 29 participants 309 participants 312 participants 650 participants
58
(25 to 75)
57
(19 to 82)
59
(21 to 82)
58
(19 to 82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 309 participants 312 participants 650 participants
Female
11
  37.9%
115
  37.2%
134
  42.9%
260
  40.0%
Male
18
  62.1%
194
  62.8%
178
  57.1%
390
  60.0%
1.Primary Outcome
Title Overall Survival (OS)
Hide Description Survival time was defined as time from randomization to date of death from any cause and was estimated by the Kaplan-Meier method. Patients last known to be alive were censored at the date of last contact. This analysis was planned to occur when 390 deaths had been reported.
Time Frame From randomization to date of death or last follow-up. Analysis occurs after all 390 deaths have been reported.
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible randomized patients
Arm/Group Title Randomized Arm 1: TMZ+RT + Placebo Randomized Arm 2: TMZ+RT + Bevacizumab
Hide Arm/Group Description:
Temozolomide post-randomization,Radiation therapy post-randomization, placebo
Temozolomide post-randomization, radiation therapy post-randomization, bevacizumab
Overall Number of Participants Analyzed 309 312
Median (95% Confidence Interval)
Unit of Measure: months
16.1
(14.8 to 18.7)
15.7
(14.2 to 16.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Arm 1: TMZ+RT + Placebo, Randomized Arm 2: TMZ+RT + Bevacizumab
Comments The trial was designed to concurrently provide 80% power for the detection of a 25% relative reduction in mortality hazard (hazard ratio .75) and 30% reduction in progression hazard (hazard ratio .70) for the addition of bevacizumab to temozolomide and radiation. To control for type I error in testing the co-primary endpoints, the significance criterion for OS was 0.023 (one-sided) and for PFS was 0.002 (one-sided).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments To control for type I error in testing the co-primary endpoints, the significance criterion for OS was 0.023 (one-sided) and for PFS was 0.002 (one-sided).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.93 to 1.37
Estimation Comments [Not Specified]
2.Primary Outcome
Title Progression-free Survival (PFS)
Hide Description Progression-free survival was defined as time from randomization to date of progression, death, or last follow-up, and was estimated by the Kaplan-Meier method. Patients last known to be alive were censored at the date of last contact. This analysis was planned to occur when 390 deaths had been reported.
Time Frame From randomization to date of progression, death, or last follow-up for progression-free survival. Analysis occurs after all 390 deaths have been reported.
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible randomized patients
Arm/Group Title Randomized Arm 1: TMZ+RT + Placebo Randomized Arm 2: TMZ+RT + Bevacizumab
Hide Arm/Group Description:
Temozolomide post-randomization,Radiation therapy post-randomization, placebo
Temozolomide post-randomization, radiation therapy post-randomization, bevacizumab
Overall Number of Participants Analyzed 309 312
Median (95% Confidence Interval)
Unit of Measure: months
7.3
(5.6 to 7.9)
10.7
(10.0 to 12.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Arm 1: TMZ+RT + Placebo, Randomized Arm 2: TMZ+RT + Bevacizumab
Comments The trial was designed to concurrently provide 80% power for the detection of a 25% relative reduction in mortality hazard (hazard ratio .75) and 30% reduction in progression hazard (hazard ratio .70) for the addition of bevacizumab to temozolomide and radiation. To control for type I error in testing the co-primary endpoints, the significance criterion for OS was 0.023 (one-sided) and for PFS was 0.002 (one-sided).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments To control for type I error in testing the co-primary endpoints, the significance criterion for OS was 0.023 (one-sided) and for PFS was 0.002 (one-sided).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.66 to 0.94
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Incidence of Grade 3 and Higher Treatment-related Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) Version 3.0
Hide Description AEs are graded by using CTCAE 3.0. The difference between the two randomized arms in the percentage of patients with grade 3 or higher toxicities reported as possibly/probably/definitely related to protocol treatment will be tested using a chi square test.
Time Frame Up to 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible randomized patients with adverse event data who started study treatment.
Arm/Group Title Randomized Arm 1: TMZ+RT + Placebo Randomized Arm 2: TMZ+RT + Bevacizumab
Hide Arm/Group Description:
Temozolomide post-randomization,Radiation therapy post-randomization, placebo
Temozolomide post-randomization, radiation therapy post-randomization, bevacizumab
Overall Number of Participants Analyzed 300 303
Measure Type: Number
Unit of Measure: participants
87 97
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Arm 1: TMZ+RT + Placebo, Randomized Arm 2: TMZ+RT + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.42
Comments Two-sided
Method Chi-squared
Comments [Not Specified]
4.Other Pre-specified Outcome
Title Quality of Life Measured by the M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT Tool) and EORTC Quality of Life Questionnaire-Core/Brain Cancer Module( QLQ-C30/BCM20)
Hide Description [Not Specified]
Time Frame Analysis can occur at or after time of primary outcome measure analysis.
Outcome Measure Data Not Reported
5.Other Pre-specified Outcome
Title Neurocognitive Function Measured by the Hopkins Verbal Learning Test-Revised(HVLT-R), Trail Making Test Part A, Trail Making Test Part B, Controlled Oral Word Association Test (COWAT)
Hide Description [Not Specified]
Time Frame Analysis can occur at or after time of primary outcome measure analysis.
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description Data is reported for eligible randomized patients with adverse event data who started study treatment. Subjects experiencing more than one of a given serious adverse event (SAE) were counted only once for that SAE. The same methodology was applied for non-serious adverse events.
 
Arm/Group Title Pre-Randomization TMZ+RT Randomized Arm 1: TMZ+RT + Placebo Randomized Arm 2: TMZ+RT + Bevacizumab
Hide Arm/Group Description Temozolomide pre-randomization, radiation therapy pre-randomization. Note that for the purpose of this table, this arm only includes patients that did not continue to randomization. Temozolomide post-randomization,Radiation therapy post-randomization, placebo Temozolomide post-randomization, radiation therapy post-randomization, bevacizumab
All-Cause Mortality
Pre-Randomization TMZ+RT Randomized Arm 1: TMZ+RT + Placebo Randomized Arm 2: TMZ+RT + Bevacizumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Pre-Randomization TMZ+RT Randomized Arm 1: TMZ+RT + Placebo Randomized Arm 2: TMZ+RT + Bevacizumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/10 (50.00%)   115/300 (38.33%)   141/303 (46.53%) 
Blood and lymphatic system disorders       
Blood disorder * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Bone marrow hypocellular * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Febrile neutropenia * 1  0/10 (0.00%)  0/300 (0.00%)  4/303 (1.32%) 
Hemoglobin decreased * 1  0/10 (0.00%)  2/300 (0.67%)  9/303 (2.97%) 
Hemolysis * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Leukopenia * 1  0/10 (0.00%)  3/300 (1.00%)  6/303 (1.98%) 
Lymphopenia * 1  0/10 (0.00%)  3/300 (1.00%)  8/303 (2.64%) 
Cardiac disorders       
Arrhythmia supraventricular * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Atrial fibrillation * 1  0/10 (0.00%)  1/300 (0.33%)  3/303 (0.99%) 
Cardiac disorder * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Left ventricular failure * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Myocardial ischemia * 1  0/10 (0.00%)  2/300 (0.67%)  2/303 (0.66%) 
Eye disorders       
Dry eye syndrome * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Eye disorder * 1  1/10 (10.00%)  2/300 (0.67%)  0/303 (0.00%) 
Retinal detachment * 1  0/10 (0.00%)  2/300 (0.67%)  0/303 (0.00%) 
Vision blurred * 1  0/10 (0.00%)  3/300 (1.00%)  0/303 (0.00%) 
Gastrointestinal disorders       
Abdominal pain * 1  0/10 (0.00%)  4/300 (1.33%)  4/303 (1.32%) 
Cecal ulcer * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Colonic perforation * 1  0/10 (0.00%)  1/300 (0.33%)  5/303 (1.65%) 
Constipation * 1  0/10 (0.00%)  7/300 (2.33%)  0/303 (0.00%) 
Diarrhea * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Dyspepsia * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Dysphagia * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Gastric ulcer * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Gastrointestinal disorder * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Intra-abdominal hemorrhage  1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Lower gastrointestinal hemorrhage  1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Mucositis oral * 1  0/10 (0.00%)  1/300 (0.33%)  1/303 (0.33%) 
Nausea * 1  0/10 (0.00%)  4/300 (1.33%)  10/303 (3.30%) 
Pancreatitis * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Small intestinal obstruction * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Upper gastrointestinal hemorrhage  1  0/10 (0.00%)  1/300 (0.33%)  1/303 (0.33%) 
Vomiting * 1  0/10 (0.00%)  2/300 (0.67%)  6/303 (1.98%) 
General disorders       
Chest pain * 1  0/10 (0.00%)  1/300 (0.33%)  2/303 (0.66%) 
Death * 1  0/10 (0.00%)  2/300 (0.67%)  8/303 (2.64%) 
Disease progression * 1  1/10 (10.00%)  5/300 (1.67%)  2/303 (0.66%) 
Edema limbs * 1  0/10 (0.00%)  1/300 (0.33%)  2/303 (0.66%) 
Fatigue * 1  0/10 (0.00%)  15/300 (5.00%)  16/303 (5.28%) 
Fever * 1  0/10 (0.00%)  5/300 (1.67%)  4/303 (1.32%) 
Gait abnormal * 1  0/10 (0.00%)  2/300 (0.67%)  2/303 (0.66%) 
Localized edema [head and neck] * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Pain [other] * 1  0/10 (0.00%)  1/300 (0.33%)  1/303 (0.33%) 
Sudden death * 1  0/10 (0.00%)  1/300 (0.33%)  1/303 (0.33%) 
Visceral edema * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Hepatobiliary disorders       
Cholecystitis * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Gallbladder pain * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Immune system disorders       
Hypersensitivity * 1  0/10 (0.00%)  1/300 (0.33%)  2/303 (0.66%) 
Infections and infestations       
Abdominal infection [with normal or Grade 1-2 ANC] * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Appendicitis [with normal or Grade 1-2 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Appendicitis perforated * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Bladder infection [with normal or Grade 1-2 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Bone infection [with normal or Grade 1-2 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Catheter related infection [with normal or Grade 1-2 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Encephalitis infection [with unknown ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Eye infection [with unknown ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Ileal infection [with normal or Grade 1-2 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Infection [neck, with Grade 3-4 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Infection [other] * 1  0/10 (0.00%)  2/300 (0.67%)  0/303 (0.00%) 
Infectious colitis [with Grade 3-4 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Infective myositis [with normal or Grade 1-2 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Mucosal infection [with unknown ANC] * 1  0/10 (0.00%)  2/300 (0.67%)  0/303 (0.00%) 
Opportunistic infection * 1  0/10 (0.00%)  0/300 (0.00%)  2/303 (0.66%) 
Pancreas infection [with normal or Grade 1-2 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Peripheral nerve infection [with normal or Grade 1-2 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Pneumonia [with Grade 3-4 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Pneumonia [with normal or Grade 1-2 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Pneumonia [with unknown ANC] * 1  0/10 (0.00%)  3/300 (1.00%)  2/303 (0.66%) 
Rhinitis infective [with unknown ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Sepsis [with Grade 3-4 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Sepsis [with unknown ANC] * 1  0/10 (0.00%)  2/300 (0.67%)  1/303 (0.33%) 
Skin infection [with normal or Grade 1-2 ANC] * 1  0/10 (0.00%)  1/300 (0.33%)  1/303 (0.33%) 
Upper aerodigestive tract infection [with normal or Grade 1-2 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Upper respiratory infection [with unknown ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Urinary tract infection [with Grade 3-4 ANC] * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Urinary tract infection [with normal or Grade 1-2 ANC] * 1  0/10 (0.00%)  1/300 (0.33%)  1/303 (0.33%) 
Urinary tract infection [with unknown ANC] * 1  0/10 (0.00%)  1/300 (0.33%)  1/303 (0.33%) 
Wound infection [with normal or Grade 1-2 ANC] * 1  1/10 (10.00%)  2/300 (0.67%)  3/303 (0.99%) 
Wound infection [with unknown ANC] * 1  1/10 (10.00%)  1/300 (0.33%)  1/303 (0.33%) 
Injury, poisoning and procedural complications       
Fracture * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Intraoperative hepatobiliary injury - Gallbladder * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Small intestinal anastomotic leak * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Vascular access complication  1  1/10 (10.00%)  0/300 (0.00%)  3/303 (0.99%) 
Wound dehiscence * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Wound dehiscence  1  1/10 (10.00%)  3/300 (1.00%)  6/303 (1.98%) 
Investigations       
Activated partial thromboplastin time prolonged * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Activated partial thromboplastin time prolonged  1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Alanine aminotransferase increased * 1  0/10 (0.00%)  2/300 (0.67%)  1/303 (0.33%) 
Amylase increased * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Aspartate aminotransferase increased * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
CD4 lymphocytes decreased * 1  0/10 (0.00%)  0/300 (0.00%)  4/303 (1.32%) 
Cardiac troponin T increased * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Creatinine increased * 1  0/10 (0.00%)  2/300 (0.67%)  3/303 (0.99%) 
Lipase increased * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Neutrophil count decreased * 1  0/10 (0.00%)  0/300 (0.00%)  5/303 (1.65%) 
Neutrophil count decreased  1  0/10 (0.00%)  3/300 (1.00%)  16/303 (5.28%) 
Platelet count decreased * 1  0/10 (0.00%)  1/300 (0.33%)  10/303 (3.30%) 
Platelet count decreased  1  0/10 (0.00%)  8/300 (2.67%)  29/303 (9.57%) 
Weight gain * 1  0/10 (0.00%)  0/300 (0.00%)  2/303 (0.66%) 
Weight loss * 1  0/10 (0.00%)  2/300 (0.67%)  1/303 (0.33%) 
Metabolism and nutrition disorders       
Anorexia * 1  1/10 (10.00%)  3/300 (1.00%)  8/303 (2.64%) 
Dehydration * 1  1/10 (10.00%)  7/300 (2.33%)  8/303 (2.64%) 
Hyperglycemia * 1  1/10 (10.00%)  8/300 (2.67%)  3/303 (0.99%) 
Hyperkalemia * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Hypoalbuminemia * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Hypocalcemia * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Hypoglycemia * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Hypokalemia * 1  0/10 (0.00%)  0/300 (0.00%)  2/303 (0.66%) 
Hyponatremia * 1  0/10 (0.00%)  4/300 (1.33%)  2/303 (0.66%) 
Musculoskeletal and connective tissue disorders       
Back pain * 1  0/10 (0.00%)  3/300 (1.00%)  0/303 (0.00%) 
Head soft tissue necrosis * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Joint pain * 1  0/10 (0.00%)  1/300 (0.33%)  1/303 (0.33%) 
Muscle weakness * 1  0/10 (0.00%)  5/300 (1.67%)  11/303 (3.63%) 
Muscle weakness left-sided * 1  0/10 (0.00%)  2/300 (0.67%)  2/303 (0.66%) 
Muscle weakness lower limb * 1  0/10 (0.00%)  3/300 (1.00%)  2/303 (0.66%) 
Muscle weakness right-sided * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Muscle weakness upper limb * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Osteonecrosis * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Pain in extremity * 1  0/10 (0.00%)  0/300 (0.00%)  2/303 (0.66%) 
Nervous system disorders       
Ataxia * 1  0/10 (0.00%)  4/300 (1.33%)  6/303 (1.98%) 
Central nervous system necrosis * 1  0/10 (0.00%)  2/300 (0.67%)  1/303 (0.33%) 
Cerebrospinal fluid leakage * 1  0/10 (0.00%)  1/300 (0.33%)  1/303 (0.33%) 
Cognitive disturbance * 1  0/10 (0.00%)  4/300 (1.33%)  3/303 (0.99%) 
Depressed level of consciousness * 1  0/10 (0.00%)  3/300 (1.00%)  3/303 (0.99%) 
Dizziness * 1  0/10 (0.00%)  0/300 (0.00%)  3/303 (0.99%) 
Encephalopathy * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Encephalopathy  1  0/10 (0.00%)  0/300 (0.00%)  3/303 (0.99%) 
Extrapyramidal disorder * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Headache * 1  1/10 (10.00%)  8/300 (2.67%)  4/303 (1.32%) 
Hydrocephalus * 1  0/10 (0.00%)  2/300 (0.67%)  1/303 (0.33%) 
Intracranial hemorrhage * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Intracranial hemorrhage  1  0/10 (0.00%)  3/300 (1.00%)  4/303 (1.32%) 
Ischemia cerebrovascular * 1  0/10 (0.00%)  4/300 (1.33%)  7/303 (2.31%) 
Leukoencephalopathy  1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Memory impairment * 1  0/10 (0.00%)  5/300 (1.67%)  2/303 (0.66%) 
Mental status changes * 1  0/10 (0.00%)  1/300 (0.33%)  2/303 (0.66%) 
Neuralgia * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Neurological disorder NOS * 1  0/10 (0.00%)  2/300 (0.67%)  1/303 (0.33%) 
Peripheral motor neuropathy * 1  0/10 (0.00%)  5/300 (1.67%)  6/303 (1.98%) 
Peripheral sensory neuropathy * 1  0/10 (0.00%)  1/300 (0.33%)  2/303 (0.66%) 
Seizure * 1  0/10 (0.00%)  23/300 (7.67%)  20/303 (6.60%) 
Speech disorder * 1  0/10 (0.00%)  8/300 (2.67%)  4/303 (1.32%) 
Syncope * 1  0/10 (0.00%)  2/300 (0.67%)  1/303 (0.33%) 
Psychiatric disorders       
Agitation * 1  0/10 (0.00%)  1/300 (0.33%)  1/303 (0.33%) 
Anxiety * 1  0/10 (0.00%)  1/300 (0.33%)  1/303 (0.33%) 
Confusion * 1  0/10 (0.00%)  10/300 (3.33%)  9/303 (2.97%) 
Depression * 1  0/10 (0.00%)  4/300 (1.33%)  4/303 (1.32%) 
Insomnia * 1  0/10 (0.00%)  0/300 (0.00%)  2/303 (0.66%) 
Psychosis * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Renal and urinary disorders       
Hemorrhage urinary tract  1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Proteinuria * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Urinary frequency * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Urinary retention * 1  0/10 (0.00%)  2/300 (0.67%)  1/303 (0.33%) 
Urogenital disorder * 1  0/10 (0.00%)  2/300 (0.67%)  0/303 (0.00%) 
Reproductive system and breast disorders       
Vaginal hemorrhage  1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Respiratory, thoracic and mediastinal disorders       
Adult respiratory distress syndrome * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Allergic rhinitis * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Atelectasis * 1  0/10 (0.00%)  1/300 (0.33%)  1/303 (0.33%) 
Bronchospasm * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Cough * 1  0/10 (0.00%)  2/300 (0.67%)  3/303 (0.99%) 
Dyspnea * 1  0/10 (0.00%)  4/300 (1.33%)  3/303 (0.99%) 
Hypoxia * 1  0/10 (0.00%)  0/300 (0.00%)  2/303 (0.66%) 
Pneumonitis * 1  0/10 (0.00%)  2/300 (0.67%)  2/303 (0.66%) 
Respiratory disorder * 1  0/10 (0.00%)  0/300 (0.00%)  2/303 (0.66%) 
Tracheal mucositis * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Skin and subcutaneous tissue disorders       
Alopecia * 1  0/10 (0.00%)  1/300 (0.33%)  1/303 (0.33%) 
Decubitus ulcer * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Erythema multiforme * 1  0/10 (0.00%)  0/300 (0.00%)  2/303 (0.66%) 
Pain of skin * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Pruritus * 1  0/10 (0.00%)  2/300 (0.67%)  0/303 (0.00%) 
Rash desquamating * 1  0/10 (0.00%)  1/300 (0.33%)  2/303 (0.66%) 
Skin disorder * 1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Skin ulceration * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Vascular disorders       
Hematoma  1  0/10 (0.00%)  1/300 (0.33%)  0/303 (0.00%) 
Hypertension * 1  0/10 (0.00%)  0/300 (0.00%)  1/303 (0.33%) 
Hypotension * 1  0/10 (0.00%)  2/300 (0.67%)  1/303 (0.33%) 
Thrombosis  1  2/10 (20.00%)  22/300 (7.33%)  23/303 (7.59%) 
Vascular disorder * 1  0/10 (0.00%)  2/300 (0.67%)  1/303 (0.33%) 
Indicates events were collected by systematic assessment
*
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%
Pre-Randomization TMZ+RT Randomized Arm 1: TMZ+RT + Placebo Randomized Arm 2: TMZ+RT + Bevacizumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/10 (70.00%)   292/300 (97.33%)   292/303 (96.37%) 
Blood and lymphatic system disorders       
Blood disorder * 1  0/10 (0.00%)  20/300 (6.67%)  19/303 (6.27%) 
Hemoglobin decreased * 1  2/10 (20.00%)  124/300 (41.33%)  111/303 (36.63%) 
Leukopenia * 1  0/10 (0.00%)  98/300 (32.67%)  119/303 (39.27%) 
Lymphopenia * 1  2/10 (20.00%)  96/300 (32.00%)  114/303 (37.62%) 
Ear and labyrinth disorders       
Hearing loss * 1  1/10 (10.00%)  18/300 (6.00%)  20/303 (6.60%) 
Tinnitus * 1  1/10 (10.00%)  16/300 (5.33%)  20/303 (6.60%) 
Eye disorders       
Eye disorder * 1  0/10 (0.00%)  25/300 (8.33%)  19/303 (6.27%) 
Vision blurred * 1  0/10 (0.00%)  47/300 (15.67%)  47/303 (15.51%) 
Gastrointestinal disorders       
Abdominal pain * 1  0/10 (0.00%)  13/300 (4.33%)  22/303 (7.26%) 
Constipation * 1  0/10 (0.00%)  126/300 (42.00%)  141/303 (46.53%) 
Diarrhea * 1  0/10 (0.00%)  48/300 (16.00%)  64/303 (21.12%) 
Dry mouth * 1  1/10 (10.00%)  15/300 (5.00%)  15/303 (4.95%) 
Dyspepsia * 1  0/10 (0.00%)  21/300 (7.00%)  27/303 (8.91%) 
Dysphagia * 1  1/10 (10.00%)  14/300 (4.67%)  15/303 (4.95%) 
Mucositis oral * 1  0/10 (0.00%)  15/300 (5.00%)  29/303 (9.57%) 
Nausea * 1  2/10 (20.00%)  165/300 (55.00%)  184/303 (60.73%) 
Vomiting * 1  0/10 (0.00%)  73/300 (24.33%)  82/303 (27.06%) 
General disorders       
Chills * 1  0/10 (0.00%)  10/300 (3.33%)  24/303 (7.92%) 
Edema limbs * 1  0/10 (0.00%)  49/300 (16.33%)  43/303 (14.19%) 
Fatigue * 1  3/10 (30.00%)  238/300 (79.33%)  243/303 (80.20%) 
Fever * 1  0/10 (0.00%)  22/300 (7.33%)  27/303 (8.91%) 
Gait abnormal * 1  0/10 (0.00%)  28/300 (9.33%)  22/303 (7.26%) 
Localized edema [head and neck] * 1  0/10 (0.00%)  21/300 (7.00%)  16/303 (5.28%) 
Pain [other] * 1  0/10 (0.00%)  20/300 (6.67%)  20/303 (6.60%) 
Infections and infestations       
Opportunistic infection * 1  1/10 (10.00%)  2/300 (0.67%)  5/303 (1.65%) 
Injury, poisoning and procedural complications       
Dermatitis radiation * 1  0/10 (0.00%)  49/300 (16.33%)  42/303 (13.86%) 
Fracture * 1  1/10 (10.00%)  4/300 (1.33%)  1/303 (0.33%) 
Radiation recall reaction (dermatologic) * 1  0/10 (0.00%)  30/300 (10.00%)  47/303 (15.51%) 
Investigations       
Alanine aminotransferase increased * 1  2/10 (20.00%)  103/300 (34.33%)  93/303 (30.69%) 
Alkaline phosphatase increased * 1  0/10 (0.00%)  30/300 (10.00%)  30/303 (9.90%) 
Aspartate aminotransferase increased * 1  0/10 (0.00%)  69/300 (23.00%)  74/303 (24.42%) 
CD4 lymphocytes decreased * 1  0/10 (0.00%)  10/300 (3.33%)  22/303 (7.26%) 
Creatinine increased * 1  1/10 (10.00%)  37/300 (12.33%)  35/303 (11.55%) 
Hyperbilirubinemia * 1  0/10 (0.00%)  19/300 (6.33%)  22/303 (7.26%) 
Laboratory test abnormal * 1  0/10 (0.00%)  39/300 (13.00%)  39/303 (12.87%) 
Neutrophil count decreased * 1  0/10 (0.00%)  19/300 (6.33%)  34/303 (11.22%) 
Neutrophil count decreased  1  0/10 (0.00%)  64/300 (21.33%)  83/303 (27.39%) 
Platelet count decreased * 1  1/10 (10.00%)  47/300 (15.67%)  59/303 (19.47%) 
Platelet count decreased  1  0/10 (0.00%)  135/300 (45.00%)  171/303 (56.44%) 
Weight gain * 1  0/10 (0.00%)  16/300 (5.33%)  4/303 (1.32%) 
Weight loss * 1  1/10 (10.00%)  39/300 (13.00%)  55/303 (18.15%) 
Metabolism and nutrition disorders       
Anorexia * 1  1/10 (10.00%)  110/300 (36.67%)  127/303 (41.91%) 
Dehydration * 1  0/10 (0.00%)  17/300 (5.67%)  23/303 (7.59%) 
Hyperglycemia * 1  2/10 (20.00%)  114/300 (38.00%)  121/303 (39.93%) 
Hyperkalemia * 1  1/10 (10.00%)  18/300 (6.00%)  24/303 (7.92%) 
Hypermagnesemia * 1  1/10 (10.00%)  3/300 (1.00%)  6/303 (1.98%) 
Hypoalbuminemia * 1  1/10 (10.00%)  53/300 (17.67%)  53/303 (17.49%) 
Hypocalcemia * 1  0/10 (0.00%)  38/300 (12.67%)  54/303 (17.82%) 
Hypoglycemia * 1  0/10 (0.00%)  14/300 (4.67%)  22/303 (7.26%) 
Hypokalemia * 1  0/10 (0.00%)  43/300 (14.33%)  46/303 (15.18%) 
Hyponatremia * 1  2/10 (20.00%)  54/300 (18.00%)  73/303 (24.09%) 
Musculoskeletal and connective tissue disorders       
Back pain * 1  0/10 (0.00%)  30/300 (10.00%)  32/303 (10.56%) 
Joint pain * 1  0/10 (0.00%)  33/300 (11.00%)  50/303 (16.50%) 
Muscle weakness * 1  0/10 (0.00%)  49/300 (16.33%)  58/303 (19.14%) 
Muscle weakness left-sided * 1  1/10 (10.00%)  15/300 (5.00%)  8/303 (2.64%) 
Muscle weakness lower limb * 1  0/10 (0.00%)  26/300 (8.67%)  24/303 (7.92%) 
Musculoskeletal disorder * 1  0/10 (0.00%)  16/300 (5.33%)  10/303 (3.30%) 
Myalgia * 1  0/10 (0.00%)  18/300 (6.00%)  29/303 (9.57%) 
Pain in extremity * 1  0/10 (0.00%)  24/300 (8.00%)  44/303 (14.52%) 
Nervous system disorders       
Acoustic nerve disorder NOS * 1  1/10 (10.00%)  4/300 (1.33%)  0/303 (0.00%) 
Ataxia * 1  0/10 (0.00%)  42/300 (14.00%)  45/303 (14.85%) 
Cognitive disturbance * 1  0/10 (0.00%)  25/300 (8.33%)  26/303 (8.58%) 
Depressed level of consciousness * 1  0/10 (0.00%)  7/300 (2.33%)  23/303 (7.59%) 
Dizziness * 1  0/10 (0.00%)  77/300 (25.67%)  75/303 (24.75%) 
Headache * 1  1/10 (10.00%)  155/300 (51.67%)  167/303 (55.12%) 
Memory impairment * 1  1/10 (10.00%)  63/300 (21.00%)  72/303 (23.76%) 
Neurological disorder NOS * 1  1/10 (10.00%)  25/300 (8.33%)  25/303 (8.25%) 
Peripheral motor neuropathy * 1  0/10 (0.00%)  43/300 (14.33%)  41/303 (13.53%) 
Peripheral sensory neuropathy * 1  0/10 (0.00%)  50/300 (16.67%)  47/303 (15.51%) 
Seizure * 1  2/10 (20.00%)  53/300 (17.67%)  61/303 (20.13%) 
Speech disorder * 1  0/10 (0.00%)  56/300 (18.67%)  36/303 (11.88%) 
Taste alteration * 1  1/10 (10.00%)  49/300 (16.33%)  54/303 (17.82%) 
Tremor * 1  0/10 (0.00%)  31/300 (10.33%)  33/303 (10.89%) 
Psychiatric disorders       
Agitation * 1  0/10 (0.00%)  27/300 (9.00%)  19/303 (6.27%) 
Anxiety * 1  0/10 (0.00%)  44/300 (14.67%)  42/303 (13.86%) 
Confusion * 1  0/10 (0.00%)  43/300 (14.33%)  41/303 (13.53%) 
Depression * 1  1/10 (10.00%)  36/300 (12.00%)  54/303 (17.82%) 
Insomnia * 1  0/10 (0.00%)  74/300 (24.67%)  75/303 (24.75%) 
Renal and urinary disorders       
Proteinuria * 1  0/10 (0.00%)  25/300 (8.33%)  28/303 (9.24%) 
Urinary frequency * 1  0/10 (0.00%)  13/300 (4.33%)  24/303 (7.92%) 
Respiratory, thoracic and mediastinal disorders       
Allergic rhinitis * 1  0/10 (0.00%)  19/300 (6.33%)  20/303 (6.60%) 
Cough * 1  0/10 (0.00%)  33/300 (11.00%)  50/303 (16.50%) 
Dyspnea * 1  0/10 (0.00%)  33/300 (11.00%)  33/303 (10.89%) 
Hemorrhage nasal * 1  0/10 (0.00%)  5/300 (1.67%)  15/303 (4.95%) 
Hemorrhage nasal  1  0/10 (0.00%)  16/300 (5.33%)  34/303 (11.22%) 
Voice alteration * 1  0/10 (0.00%)  6/300 (2.00%)  23/303 (7.59%) 
Skin and subcutaneous tissue disorders       
Acne * 1  0/10 (0.00%)  11/300 (3.67%)  17/303 (5.61%) 
Alopecia * 1  1/10 (10.00%)  140/300 (46.67%)  169/303 (55.78%) 
Dry skin * 1  0/10 (0.00%)  17/300 (5.67%)  22/303 (7.26%) 
Pruritus * 1  0/10 (0.00%)  36/300 (12.00%)  35/303 (11.55%) 
Rash desquamating * 1  0/10 (0.00%)  36/300 (12.00%)  41/303 (13.53%) 
Skin disorder * 1  0/10 (0.00%)  15/300 (5.00%)  13/303 (4.29%) 
Vascular disorders       
Hypertension * 1  1/10 (10.00%)  39/300 (13.00%)  67/303 (22.11%) 
Thrombosis  1  2/10 (20.00%)  24/300 (8.00%)  18/303 (5.94%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Wendy Seiferheld, M.S.
Organization: NRG Oncology
EMail: seiferheldw@nrgoncology.org
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00884741    
Other Study ID Numbers: NCI-2009-01670
NCI-2009-01670 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RTOG-0825
RTOG 0825
CDR0000640428
RTOG-0825 ( Other Identifier: NRG Oncology )
RTOG-0825 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
U10CA021661 ( U.S. NIH Grant/Contract )
First Submitted: April 18, 2009
First Posted: April 21, 2009
Results First Submitted: December 18, 2015
Results First Posted: October 12, 2016
Last Update Posted: July 24, 2019