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

View this study on the modernized ClinicalTrials.gov

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

Participant Flow

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
Arm/Group Description	No treatment. Central Pathology Tis...	Temozolomide pre-randomization, rad...	Temozolomide post-randomization,Rad...	Temozolomide post-randomization, ra...
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.

Baseline Characteristics

Arm/Group Title		Pre-Randomization TMZ+RT	Randomized Arm 1: TMZ+RT + Placebo	Randomized Arm 2: TMZ+RT + Bevacizumab	Total
Arm/Group Description		Temozolomide pre-randomization, rad...	Temozolomide post-randomization,Rad...	Temozolomide post-randomization, ra...	Total of all reporting groups
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
Baseline Analysis Population Description		...
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%

Outcome Measures

1.Primary Outcome


Title	Overall Survival (OS)
Description	Survival time was defined as time from randomization to date of death ...
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.

Outcome Measure Data

Analysis Population Description

All eligible randomized patients


Arm/Group Title	Randomized Arm 1: TMZ+RT + Placebo	Randomized Arm 2: TMZ+RT + Bevacizumab
Arm/Group Description:	Temozolomide post-randomization,Rad...	Temozolomide post-randomization, ra...
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)

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)
Description	Progression-free survival was defined as time from randomization to da...
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.

Outcome Measure Data

Analysis Population Description

All eligible randomized patients


Arm/Group Title	Randomized Arm 1: TMZ+RT + Placebo	Randomized Arm 2: TMZ+RT + Bevacizumab
Arm/Group Description:	Temozolomide post-randomization,Rad...	Temozolomide post-randomization, ra...
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)

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
Description	AEs are graded by using CTCAE 3.0. The difference between the two rand...
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

Outcome Measure Data

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
Arm/Group Description:	Temozolomide post-randomization,Rad...	Temozolomide post-randomization, ra...
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

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)
Description	[Not Specified]
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)
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Analysis can occur at or after time of primary outcome measure analysis.

Outcome Measure Data Not Reported

Adverse Events

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
Arm/Group Description	Temozolomide pre-randomization, rad...	Temozolomide post-randomization,Rad...	Temozolomide post-randomization, ra...
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	--/--	--/--	--/--
Serious Adverse Events 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)
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)

Limitations and Caveats

[Not Specified]

More Information

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):699-708. doi: 10.1056/NEJMoa1308573.

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

To Top