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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00884741
• Collaborator: Radiation Therapy Oncology Group (Other), NRG Oncology (Other)
• Enrollment: 637
• Locations: 330
• Arms: 2
• Actual Duration (Months): 47
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase III trial studies temozolomide (TMZ) and radiation therapy (RT) to compare how well they work with or without bevacizumab in treating patients with newly diagnosed glioblastoma or gliosarcoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as bevacizumab, may find tumor cells and help kill them. It is not yet known whether temozolomide and radiation therapy are more effective when given together with or without bevacizumab in treating glioblastoma or gliosarcoma.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma; Gliosarcoma; Supratentorial Glioblastoma	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	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To determine whether the addition of bevacizumab to temozolomide and radiation improves efficacy as measured by progression-free and/or overall survival.

2. To assess the association between overall survival and K^trans change from T1 to T2. (ACRIN 6686) III. To assess the association between overall survival and spin echo cerebral blood volume (CBV) change from T1 to T2. (ACRIN 6686)

SECONDARY OBJECTIVES:

1. To determine whether the tumor molecular profile conferring a mesenchymal/angiogenic phenotype is associated with a selective increase in benefit, as measured by either overall survival or progression-free survival, from the addition of bevacizumab.

2. To compare and record the toxicities of the conventional and bevacizumab-containing regimens.

3. To assess the association between progression-free survival and K^{trans change from T1 to T2. (ACRIN 6686) IV. To assess the association between progression-free survival and spin echo CBV change from T1 to T2. (ACRIN 6686) V. To assess the association between values of K}trans and spin echo CBV measured separately at T0 and at T1, and overall and progression-free survival. (ACRIN 6686) VI. To assess the association between overall survival and K^trans changes from T0 to T1 and from T2 to T3. (ACRIN 6686) VII. To assess the association between overall survival and spin echo CBV changes from T0 to T1 and from T2 to T3. (ACRIN 6686) VIII. To assess the association between overall survival and apparent diffusion coefficient (ADC) change from T0 to T1. (ACRIN 6686) IX. To assess the association between overall survival and ADC change from T1 to T2. (ACRIN 6686) X. To assess the association between progression-free survival and ADC change from T0 to T1. (ACRIN 6686) XI. To assess the association between progression-free survival and ADC change from T1 to T2. (ACRIN 6686) XII. To assess the association between T1 values of ADC and overall and progression-free survival. (ACRIN 6686) XIII. To assess the association between change in lesion size between T1 and T3, as measured by advanced magnetic resonance imaging (MRI), and overall and progression-free survival. (ACRIN 6686)

TERTIARY OBJECTIVES:

1. To determine the differential acute effects associated with the addition of bevacizumab to temozolomide and radiation, as compared to the conventional arm, on measures of neurocognitive function, health-related quality of life, and symptoms during radiation and across the longitudinal progression-free interval.

2. To determine the relationship of neurocognitive function, health-related quality of life, and symptoms, with progression-free and overall survival.

3. To determine the association between tumor molecular profile (i.e., mesenchymal/angiogenic phenotype and proneural phenotype) and neurocognitive function, health-related quality of life, and symptoms.

4. To describe the association between health-related quality of life as measured by the European Organization for Research and Treatment Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTC-QL30/BCM20) and mean symptom severity as measured by the M. D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) in patients enrolled in this study.

5. To evaluate the relationship between self-reported neurocognitive function and objectively measured tests of neurocognitive function (NCF).

6. To assess the association between measures of change in enhancing tumor size at week 22 and overall survival in participants with glioma receiving chemoradiotherapy with and without bevacizumab.

7. To assess the association between measures of change in T2-based tumor size at week 22 and overall survival in participants with glioma receiving chemoradiotherapy with and without bevacizumab.

8. To assess the association between changes in ADC values and overall survival in participants with glioma receiving chemoradiotherapy with and without bevacizumab.

OUTLINE: Patients are randomized to 1 of 2 treatment arms (there are also two registration steps prior to randomization which are labeled as "arms" in ClinicalTrials.gov to facilitate entry of results into the website).

ARM I: Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide orally (PO) once daily (QD) for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide.

ARM II: Patients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 637 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase III Double-blind Placebo-Controlled Trial of Conventional Concurrent Chemoradiation and Adjuvant Temozolomide Plus Bevacizumab Versus Conventional Concurrent Chemoradiation and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma
• Actual Study Start Date: Apr 15, 2009
• Actual Primary Completion Date: Mar 17, 2013
• Actual Study Completion Date: Mar 17, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (radiation therapy, temozolomide, placebo) Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide PO QD for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide.	Radiation: 3-Dimensional Conformal Radiation Therapy; Undergo 3-dimentional conformal radiation therapy; Other Names: 3-dimensional radiation therapy 3D CONFORMAL RADIATION THERAPY 3D CRT 3D-CRT Conformal Therapy Radiation Conformal Therapy ; Radiation: Intensity-Modulated Radiation Therapy; Undergo intensity-modulated radiation therapy; Other Names: IMRT Intensity Modulated RT Intensity-Modulated Radiotherapy ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Placebo; Given IV; Other Names: placebo therapy PLCB sham therapy ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Drug: Temozolomide; Given orally; Other Names: CCRG-81045 Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo- M & B 39831 M and B 39831 Methazolastone RP-46161 SCH 52365 Temcad Temodal Temodar Temomedac
Experimental: Arm II (radiation therapy, temozolomide, bevacizumab) Patients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.	Radiation: 3-Dimensional Conformal Radiation Therapy; Undergo 3-dimentional conformal radiation therapy; Other Names: 3-dimensional radiation therapy 3D CONFORMAL RADIATION THERAPY 3D CRT 3D-CRT Conformal Therapy Radiation Conformal Therapy ; Biological: Bevacizumab; Given IV; Other Names: Anti-VEGF Anti-VEGF Humanized Monoclonal Antibody Anti-VEGF rhuMAb Avastin Bevacizumab Biosimilar BEVZ92 Bevacizumab Biosimilar BI 695502 Bevacizumab Biosimilar CBT 124 Bevacizumab Biosimilar FKB238 BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer Recombinant Humanized Anti-VEGF Monoclonal Antibody rhuMab-VEGF ; Radiation: Intensity-Modulated Radiation Therapy; Undergo intensity-modulated radiation therapy; Other Names: IMRT Intensity Modulated RT Intensity-Modulated Radiotherapy ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Drug: Temozolomide; Given orally; Other Names: CCRG-81045 Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo- M & B 39831 M and B 39831 Methazolastone RP-46161 SCH 52365 Temcad Temodal Temodar Temomedac

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [From randomization to date of death or last follow-up. Analysis occurs after all 390 deaths have been reported.]

   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.

2. Progression-free Survival (PFS) [From randomization to date of progression, death, or last follow-up for progression-free survival. Analysis occurs after all 390 deaths have been reported.]

   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.

Secondary Outcome Measures

1. 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 [Up to 30 days]

   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.

Other Outcome Measures

1. 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) [Analysis can occur at or after time of primary outcome measure analysis.]

2. 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) [Analysis can occur at or after time of primary outcome measure analysis.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) confirmed by central review prior to step 2 registration

• Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient size for analysis of O-6-methylguanine-DNA methyltransferase (MGMT) and determination of molecular profile

• Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged to maximize the chances of eligibility; at least 1 cubic centimeter of tissue composed primarily of tumor must be present

• CUSA (Cavitron ultrasonic aspirator)-derived material is not allowed; fresh frozen tumor tissue acquisition is encouraged

• Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy is not allowed because it will not provide sufficient tissue for MGMT analysis

• The tumor tissue should be sent as soon as possible to maximize the likelihood of eligibility; tumor tissue should be submitted by 4 weeks after the surgical procedure so that the study registration and treatment can commence by the mandatory 5 week post-surgery outer limit

• Sites must submit tissue fir central review in order to obtain the MGMT analysis; patients from sites not following protocol-specified process for obtaining MGMT results will be made ineligible

• The tumor must have a supratentorial component

• History/physical examination within 14 days prior to step 2 registration

• The patient must have recovered from the effects of surgery, postoperative infection, and other complications before step 2 registration

• A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively prior to the initiation of radiotherapy; the postoperative scan must be performed within 28 days prior to step 1 registration

• An MRI or computed tomography (CT) scan (potentially in addition to the postoperative scan) must be obtained within 10 days prior to the start of radiation therapy and must not demonstrate significant postoperative hemorrhage defined as > 1 cm diameter of blood; if > 1 cm of acute blood is detected, the patient will be ineligible for this trial; the radiation planning MRI or CT scan may be used to determine presence of hemorrhage

• Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided pre- and postoperative contrast-enhanced CT scans are obtained and are of sufficient quality; preoperative and postoperative scans must be the same type; such patients cannot be enrolled into the advanced imaging component

• Documentation of steroid doses within 14 days prior to step 2 registration

• Karnofsky performance status >= 70

• Absolute neutrophil count (ANC) >= 1,800 cells/mm^3

• Platelets >= 100,000 cells/mm^3

• Hemoglobin >= 10.0 g/dL (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable)

• Blood urea nitrogen (BUN) =< 30 mg/dL within 14 days prior to step 2 registration

• Creatinine =< 1.7 mg/dl within 14 days prior to step 2 registration

• Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio; for UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg

• Bilirubin =< 2.0 mg/dl within 14 days prior to step 2 registration

• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3 x normal range within 14 days prior to step 2 registration

• Systolic blood pressure =< 160 mg Hg or diastolic pressure =< 90 mm Hg within 14 days prior to step 2 registration

• Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior to step 2 registration

• Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to step 2 registration

• Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight [LMW] heparin) must meet both of the following criteria:

• No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)

• In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of LMW heparin

• Patient must provide study specific informed consent prior to study entry

• Women of childbearing potential and male participants must practice adequate contraception

• For females of child-bearing potential, negative serum pregnancy test within 14 days prior to step 2 registration

Exclusion Criteria:

• Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for >= 3 years; (for example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible)

• Recurrent or multifocal malignant gliomas

• Metastases detected below the tentorium or beyond the cranial vault

• Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide or bevacizumab; prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted

• Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields

• Severe, active co-morbidity, defined as follows:

• Unstable angina and/or congestive heart failure within the last 6 months

• Transmural myocardial infarction within the last 6 months

• Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days of step 2 registration

• New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to step 2 registration

• History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months

• Serious and inadequately controlled cardiac arrhythmia

• Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease

• Evidence of bleeding diathesis or coagulopathy

• Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to step 2 registration, with the exception of the craniotomy for tumor resection

• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration

• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol

• Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive

• Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity

• Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy

• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

• Pregnant or lactating women

• Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study

• For American College of Radiology Imaging Network (ACRIN) 6686 Advanced Imaging: inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Providence Hospital	Mobile	Alabama	United States	36608
2	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
3	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
4	Arizona Oncology Services Foundation	Scottsdale	Arizona	United States	85260
5	Arizona Oncology Associates-West Orange Grove	Tucson	Arizona	United States	85704
6	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California	United States	95603
7	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
8	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California	United States	95682
9	Mercy San Juan Medical Center	Carmichael	California	United States	95608
10	John Muir Medical Center-Concord Campus	Concord	California	United States	94520
11	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
12	California Cancer Center - North Fresno	Fresno	California	United States	93720
13	Cancer Care Associates of Fresno Medical Group Inc	Fresno	California	United States	93720
14	Saint Jude Medical Center	Fullerton	California	United States	92835
15	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
16	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
17	Memorial Medical Center	Modesto	California	United States	95355
18	Bay Area Tumor Institute	Oakland	California	United States	94609
19	Kaiser Permanente Oakland-Broadway	Oakland	California	United States	94611
20	Saint Joseph Hospital - Orange	Orange	California	United States	92868
21	Pomona Valley Hospital Medical Center	Pomona	California	United States	91767
22	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California	United States	95670
23	Rohnert Park Cancer Center	Rohnert Park	California	United States	94928
24	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California	United States	95661
25	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California	United States	95678
26	Sutter Medical Center Sacramento	Sacramento	California	United States	95816
27	Mercy General Hospital Radiation Oncology Center	Sacramento	California	United States	95819
28	South Sacramento Cancer Center	Sacramento	California	United States	95823
29	University of California San Diego	San Diego	California	United States	92103
30	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94115
31	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
32	Kaiser Permanente Cancer Treatment Center	South San Francisco	California	United States	94080
33	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California	United States	95687
34	John Muir Medical Center-Walnut Creek	Walnut Creek	California	United States	94598
35	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado	United States	80012
36	Boulder Community Hospital	Boulder	Colorado	United States	80301
37	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
38	Porter Adventist Hospital	Denver	Colorado	United States	80210
39	Swedish Medical Center	Englewood	Colorado	United States	80113
40	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
41	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado	United States	80120
42	North Suburban Medical Center	Thornton	Colorado	United States	80229
43	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
44	Saint Vincent's Medical Center	Bridgeport	Connecticut	United States	06606
45	Hartford Hospital	Hartford	Connecticut	United States	06102
46	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
47	Yale University	New Haven	Connecticut	United States	06520
48	William Backus Hospital	Norwich	Connecticut	United States	06360
49	Broward Health Medical Center	Fort Lauderdale	Florida	United States	33316
50	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida	United States	33021
51	Integrated Community Oncology Network-Florida Cancer Center Beaches	Jacksonville Beach	Florida	United States	32250
52	Baptist MD Anderson Cancer Center	Jacksonville	Florida	United States	32207
53	Integrated Community Oncology Network-Southside Cancer Center	Jacksonville	Florida	United States	32207
54	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
55	Baptist Medical Center South	Jacksonville	Florida	United States	32258
56	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
57	Baptist Hospital of Miami	Miami	Florida	United States	33176
58	21st Century Oncology-Orange Park	Orange Park	Florida	United States	32073
59	Florida Hospital Orlando	Orlando	Florida	United States	32803
60	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
61	21st Century Oncology-Palatka	Palatka	Florida	United States	32177
62	Sacred Heart Hospital	Pensacola	Florida	United States	32504
63	Integrated Community Oncology Network-Flager Cancer Center	Saint Augustine	Florida	United States	32086
64	Robert and Carol Weissman Cancer Center at Martin Health	Stuart	Florida	United States	34994
65	Piedmont Hospital	Atlanta	Georgia	United States	30309
66	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	United States	30322
67	John B Amos Cancer Center	Columbus	Georgia	United States	31904
68	Dekalb Medical Center	Decatur	Georgia	United States	30033
69	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia	United States	30501
70	Southern Regional Medical Center	Riverdale	Georgia	United States	30274
71	Memorial University Medical Center	Savannah	Georgia	United States	31404
72	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
73	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
74	Northwest Community Hospital	Arlington Heights	Illinois	United States	60005
75	Northwestern University	Chicago	Illinois	United States	60611
76	John H Stroger Jr Hospital of Cook County	Chicago	Illinois	United States	60612
77	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
78	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
79	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
80	Loyola University Medical Center	Maywood	Illinois	United States	60153
81	Trinity Medical Center	Moline	Illinois	United States	61265
82	Edward Hospital/Cancer Center	Naperville	Illinois	United States	60540
83	Advocate Lutheran General Hospital	Park Ridge	Illinois	United States	60068
84	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61603
85	Memorial Medical Center	Springfield	Illinois	United States	62781
86	IU Health Bloomington	Bloomington	Indiana	United States	47403
87	Radiation Oncology Associates PC	Fort Wayne	Indiana	United States	46804
88	Parkview Hospital Randallia	Fort Wayne	Indiana	United States	46805
89	IU Health Methodist Hospital	Indianapolis	Indiana	United States	46202
90	Community Cancer Center East	Indianapolis	Indiana	United States	46219
91	IU Health Central Indiana Cancer Centers-East	Indianapolis	Indiana	United States	46219
92	Community Cancer Center North	Indianapolis	Indiana	United States	46256
93	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
94	IU Health Ball Memorial Hospital	Muncie	Indiana	United States	47303
95	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
96	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa	United States	50010
97	Physicians' Clinic of Iowa PC	Cedar Rapids	Iowa	United States	52402
98	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
99	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
100	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
101	Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
102	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
103	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas	United States	66210
104	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas	United States	66208
105	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
106	Wesley Medical Center	Wichita	Kansas	United States	67214
107	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky	United States	40202
108	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
109	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
110	Louisiana State University Health Sciences Center Shreveport	Shreveport	Louisiana	United States	71103
111	Central Maine Medical Center	Lewiston	Maine	United States	04240
112	Maine Medical Center- Scarborough Campus	Scarborough	Maine	United States	04074
113	Anne Arundel Medical Center	Annapolis	Maryland	United States	21401
114	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
115	Saint Agnes Hospital	Baltimore	Maryland	United States	21229
116	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
117	Saint Anne's Hospital	Fall River	Massachusetts	United States	02721
118	Cape Cod Hospital	Hyannis	Massachusetts	United States	02601
119	Lowell General Hospital	Lowell	Massachusetts	United States	01854
120	D'Amour Center for Cancer Care	Springfield	Massachusetts	United States	01107
121	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
122	Beaumont Hospital-Dearborn	Dearborn	Michigan	United States	48124
123	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
124	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
125	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
126	Sparrow Hospital	Lansing	Michigan	United States	48912
127	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
128	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
129	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
130	Sanford Clinic North-Bemidgi	Bemidji	Minnesota	United States	56601
131	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
132	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
133	Saint Luke's Hospital of Duluth	Duluth	Minnesota	United States	55805
134	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
135	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
136	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
137	Mayo Clinic	Rochester	Minnesota	United States	55905
138	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
139	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
140	Regions Hospital	Saint Paul	Minnesota	United States	55101
141	United Hospital	Saint Paul	Minnesota	United States	55102
142	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
143	Singing River Hospital	Pascagoula	Mississippi	United States	39581
144	Cape Radiation Oncology	Cape Girardeau	Missouri	United States	63703
145	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri	United States	63141
146	Truman Medical Center	Kansas City	Missouri	United States	64108
147	The University of Kansas Cancer Center-South	Kansas City	Missouri	United States	64131
148	The University of Kansas Cancer Center-North	Kansas City	Missouri	United States	64154
149	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
150	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri	United States	63376
151	Billings Clinic Cancer Center	Billings	Montana	United States	59101
152	CHI Health Good Samaritan	Kearney	Nebraska	United States	68847
153	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska	United States	68510
154	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
155	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
156	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
157	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
158	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
159	Renown Regional Medical Center	Reno	Nevada	United States	89502
160	Concord Hospital	Concord	New Hampshire	United States	03301
161	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
162	Elliot Hospital	Manchester	New Hampshire	United States	03103
163	Saint Barnabas Medical Center	Livingston	New Jersey	United States	07039
164	Monmouth Medical Center	Long Branch	New Jersey	United States	07740
165	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
166	Riverview Medical Center/Booker Cancer Center	Red Bank	New Jersey	United States	07701
167	Sparta Cancer Treatment Center	Sparta	New Jersey	United States	07871
168	Lovelace Medical Center-Downtown	Albuquerque	New Mexico	United States	87102
169	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
170	New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico	United States	87109
171	New York Oncology Hematology PC - Albany	Albany	New York	United States	12206
172	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467-2490
173	Maimonides Medical Center	Brooklyn	New York	United States	11219
174	Sands Cancer Center	Canandaigua	New York	United States	14424
175	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
176	South Nassau Communities	Oceanside	New York	United States	11572
177	Hudson Valley Oncology Associates	Poughkeepsie	New York	United States	12601
178	Highland Hospital	Rochester	New York	United States	14620
179	University Radiation Oncology	Rochester	New York	United States	14626
180	University of Rochester	Rochester	New York	United States	14642
181	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
182	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
183	Mission Hospital-Memorial Campus	Asheville	North Carolina	United States	28801
184	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
185	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
186	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
187	FirstHealth of the Carolinas-Moore Regional Hosiptal	Pinehurst	North Carolina	United States	28374
188	Duke Women's Cancer Care Raleigh	Raleigh	North Carolina	United States	27607
189	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina	United States	27103
190	Southeast Clinical Oncology Research (SCOR) Consortium NCORP	Winston-Salem	North Carolina	United States	27104
191	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
192	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio	United States	44304
193	Akron General Medical Center	Akron	Ohio	United States	44307
194	Summa Barberton Hospital	Barberton	Ohio	United States	44203
195	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio	United States	44122
196	Mercy Medical Center	Canton	Ohio	United States	44708
197	Aultman Health Foundation	Canton	Ohio	United States	44710
198	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio	United States	45219
199	Case Western Reserve University	Cleveland	Ohio	United States	44106
200	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
201	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
202	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
203	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
204	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
205	Grant Medical Center	Columbus	Ohio	United States	43215
206	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
207	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
208	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
209	Lake University Ireland Cancer Center	Mentor	Ohio	United States	44060
210	Southwest General Health Center Ireland Cancer Center	Middleburg Heights	Ohio	United States	44130
211	Saint Charles Hospital	Oregon	Ohio	United States	43616
212	Cancer Care Center, Incorporated	Salem	Ohio	United States	44460
213	North Coast Cancer Care	Sandusky	Ohio	United States	44870
214	Trinity's Tony Teramana Cancer Center	Steubenville	Ohio	United States	43952
215	Flower Hospital	Sylvania	Ohio	United States	43560
216	Mercy Saint Anne Hospital	Toledo	Ohio	United States	43623
217	University Pointe	West Chester	Ohio	United States	45069
218	UHHS-Westlake Medical Center	Westlake	Ohio	United States	44145
219	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
220	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma	United States	74136
221	Willamette Valley Cancer Center	Eugene	Oregon	United States	97401
222	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon	United States	97210
223	Providence Portland Medical Center	Portland	Oregon	United States	97213
224	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
225	Salem Hospital	Salem	Oregon	United States	97301
226	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
227	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
228	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania	United States	15009
229	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania	United States	18015
230	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
231	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
232	Northeast Radiation Oncology Center	Dunmore	Pennsylvania	United States	18512
233	Pocono Medical Center	East Stroudsburg	Pennsylvania	United States	18301
234	The Regional Cancer Center	Erie	Pennsylvania	United States	16505
235	Fox Chase Cancer Center Buckingham	Furlong	Pennsylvania	United States	18925
236	Adams Cancer Center	Gettysburg	Pennsylvania	United States	17325
237	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania	United States	15601
238	Cherry Tree Cancer Center	Hanover	Pennsylvania	United States	17331
239	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
240	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania	United States	15901
241	Armstrong Center for Medicine and Health	Kittanning	Pennsylvania	United States	16201
242	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17604
243	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania	United States	15132
244	Intercommunity Cancer Center	Monroeville	Pennsylvania	United States	15146
245	Allegheny Valley Hospital	Natrona Heights	Pennsylvania	United States	15065
246	UPMC Jameson	New Castle	Pennsylvania	United States	16105
247	Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301
248	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
249	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
250	Aria Health-Torresdale Campus	Philadelphia	Pennsylvania	United States	19114
251	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
252	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania	United States	15232
253	UPMC Jefferson Regional Radiation Oncology	Pittsburgh	Pennsylvania	United States	15236
254	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania	United States	15237
255	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania	United States	16346
256	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania	United States	15301
257	Reading Hospital	West Reading	Pennsylvania	United States	19611
258	Lankenau Medical Center	Wynnewood	Pennsylvania	United States	19096
259	WellSpan Health-York Hospital	York	Pennsylvania	United States	17403
260	Rhode Island Hospital	Providence	Rhode Island	United States	02903
261	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
262	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
263	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota	United States	57104
264	Erlanger Medical Center	Chattanooga	Tennessee	United States	37403
265	Jackson-Madison County General Hospital	Jackson	Tennessee	United States	38301
266	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
267	Texas Oncology-Arlington South	Arlington	Texas	United States	76014
268	Texas Oncology Bedford	Bedford	Texas	United States	76022
269	Saint Joseph Regional Cancer Center	Bryan	Texas	United States	77802
270	Texas Oncology Methodist Charlton Cancer Center	Dallas	Texas	United States	75237
271	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
272	Texas Oncology-Denton South	Denton	Texas	United States	76210
273	The Klabzuba Cancer Center	Fort Worth	Texas	United States	76104
274	University of Texas Medical Branch	Galveston	Texas	United States	77555-0565
275	M D Anderson Cancer Center	Houston	Texas	United States	77030
276	Texas Oncology-Longview Cancer Center	Longview	Texas	United States	75601
277	Covenant Medical Center-Lakeside	Lubbock	Texas	United States	79410
278	West Texas Cancer Center	Odessa	Texas	United States	79761
279	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
280	Texas Cancer Center-Sherman	Sherman	Texas	United States	75090
281	Texas Oncology Cancer Center Sugar Land	Sugar Land	Texas	United States	77479
282	Tyler Cancer Center	Tyler	Texas	United States	75702
283	Intermountain Medical Center	Murray	Utah	United States	84107
284	McKay-Dee Hospital Center	Ogden	Utah	United States	84403
285	Utah Valley Regional Medical Center	Provo	Utah	United States	84604
286	Dixie Medical Center Regional Cancer Center	Saint George	Utah	United States	84770
287	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah	United States	84106
288	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
289	LDS Hospital	Salt Lake City	Utah	United States	84143
290	University of Vermont Medical Center	Burlington	Vermont	United States	05401
291	Inova Alexandria Hospital	Alexandria	Virginia	United States	22304
292	Sentara Norfolk General Hospital	Norfolk	Virginia	United States	23507
293	Naval Medical Center - Portsmouth	Portsmouth	Virginia	United States	23708-2197
294	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
295	Harrison Medical Center	Bremerton	Washington	United States	98310
296	Virginia Mason Medical Center	Seattle	Washington	United States	98101
297	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
298	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
299	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
300	Compass Oncology Vancouver	Vancouver	Washington	United States	98684
301	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
302	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia	United States	26003
303	Langlade Hospital and Cancer Center	Antigo	Wisconsin	United States	54409
304	Radiology Associates of Appleton/ThedaCare Regional Medical Center	Appleton	Wisconsin	United States	54911
305	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
306	Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
307	Bellin Memorial Hospital	Green Bay	Wisconsin	United States	54301
308	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
309	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
310	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin	United States	53038
311	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
312	Dean Hematology and Oncology Clinic	Madison	Wisconsin	United States	53717
313	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
314	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
315	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
316	Marshfield Medical Center	Marshfield	Wisconsin	United States	54449
317	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
318	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
319	Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
320	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin	United States	53188
321	Aspirus Regional Cancer Center	Wausau	Wisconsin	United States	54401
322	Diagnostic and Treatment Center	Weston	Wisconsin	United States	54476
323	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
324	Aspirus UW Cancer Center	Wisconsin Rapids	Wisconsin	United States	54494
325	Doctor H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador	Canada	A1B 3V6
326	Health Sciences North	Sudbury	Ontario	Canada	P3E 5J1
327	CHUM - Hopital Notre-Dame	Montreal	Quebec	Canada	H2L 4M1
328	McGill University Department of Oncology	Montreal	Quebec	Canada	H2W 1S6
329	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
330	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239

Sponsors and Collaborators

• National Cancer Institute (NCI)
• Radiation Therapy Oncology Group
• NRG Oncology

Investigators

• Principal Investigator: Mark Gilbert, NRG Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00884741
• Other Study ID Numbers: NCI-2009-01670; NCI-2009-01670; RTOG-0825; RTOG 0825; CDR0000640428; RTOG-0825; RTOG-0825; U10CA180868; U10CA021661
• First Posted: Apr 21, 2009
• Last Update Posted: Jul 24, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Glioblastoma; Gliosarcoma; Bevacizumab; Antineoplastic Agents, Immunological; Temozolomide; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G

Study Results

Participant Flow

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 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
Period Title: Step 1 Registration: Tissue Screening
STARTED	0	666	0	0
COMPLETED	0	637	0	0
NOT COMPLETED	0	29	0	0
Period Title: Step 1 Registration: Tissue Screening
STARTED	0	0	317	320
COMPLETED	0	0	309	312
NOT COMPLETED	0	0	8	8

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, 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 Participants	29	309	312	650
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58	57	59	58
Sex: Female, Male (Count of Participants)
Female	11 37.9%	115 37.2%	134 42.9%	260 40%
Male	18 62.1%	194 62.8%	178 57.1%	390 60%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
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,Radiation therapy post-randomization, placebo	Temozolomide post-randomization, radiation therapy post-randomization, bevacizumab
Measure Participants	309	312
Median (95% Confidence Interval) [months]	16.1	15.7

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
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
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.93 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Progression-free Survival (PFS)
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,Radiation therapy post-randomization, placebo	Temozolomide post-randomization, radiation therapy post-randomization, bevacizumab
Measure Participants	309	312
Median (95% Confidence Interval) [months]	7.3	10.7

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
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
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.66 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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,Radiation therapy post-randomization, placebo	Temozolomide post-randomization, radiation therapy post-randomization, bevacizumab
Measure Participants	300	303
Number [participants]	87 300%	97 31.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Randomized Arm 1: TMZ+RT + Placebo, Randomized Arm 2: TMZ+RT + Bevacizumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments	Two-sided
	Method	Chi-squared
	Comments

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)
Time Frame	Analysis can occur at or after time of primary outcome measure analysis.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

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)
Time Frame	Analysis can occur at or after time of primary outcome measure analysis.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

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, 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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Pre-Randomization TMZ+RT		Randomized Arm 1: TMZ+RT + Placebo		Randomized Arm 2: TMZ+RT + Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/10 (50%)		115/300 (38.3%)		141/303 (46.5%)
Blood and lymphatic system disorders
Blood disorder	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Bone marrow hypocellular	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Febrile neutropenia	0/10 (0%)		0/300 (0%)		4/303 (1.3%)
Hemoglobin decreased	0/10 (0%)		2/300 (0.7%)		9/303 (3%)
Hemolysis	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Leukopenia	0/10 (0%)		3/300 (1%)		6/303 (2%)
Lymphopenia	0/10 (0%)		3/300 (1%)		8/303 (2.6%)
Cardiac disorders
Arrhythmia supraventricular	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Atrial fibrillation	0/10 (0%)		1/300 (0.3%)		3/303 (1%)
Cardiac disorder	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Left ventricular failure	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Myocardial ischemia	0/10 (0%)		2/300 (0.7%)		2/303 (0.7%)
Eye disorders
Dry eye syndrome	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Eye disorder	1/10 (10%)		2/300 (0.7%)		0/303 (0%)
Retinal detachment	0/10 (0%)		2/300 (0.7%)		0/303 (0%)
Vision blurred	0/10 (0%)		3/300 (1%)		0/303 (0%)
Gastrointestinal disorders
Abdominal pain	0/10 (0%)		4/300 (1.3%)		4/303 (1.3%)
Cecal ulcer	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Colonic perforation	0/10 (0%)		1/300 (0.3%)		5/303 (1.7%)
Constipation	0/10 (0%)		7/300 (2.3%)		0/303 (0%)
Diarrhea	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Dyspepsia	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Dysphagia	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Gastric ulcer	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Gastrointestinal disorder	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Intra-abdominal hemorrhage	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Lower gastrointestinal hemorrhage	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Mucositis oral	0/10 (0%)		1/300 (0.3%)		1/303 (0.3%)
Nausea	0/10 (0%)		4/300 (1.3%)		10/303 (3.3%)
Pancreatitis	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Small intestinal obstruction	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Upper gastrointestinal hemorrhage	0/10 (0%)		1/300 (0.3%)		1/303 (0.3%)
Vomiting	0/10 (0%)		2/300 (0.7%)		6/303 (2%)
General disorders
Chest pain	0/10 (0%)		1/300 (0.3%)		2/303 (0.7%)
Death	0/10 (0%)		2/300 (0.7%)		8/303 (2.6%)
Disease progression	1/10 (10%)		5/300 (1.7%)		2/303 (0.7%)
Edema limbs	0/10 (0%)		1/300 (0.3%)		2/303 (0.7%)
Fatigue	0/10 (0%)		15/300 (5%)		16/303 (5.3%)
Fever	0/10 (0%)		5/300 (1.7%)		4/303 (1.3%)
Gait abnormal	0/10 (0%)		2/300 (0.7%)		2/303 (0.7%)
Localized edema [head and neck]	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Pain [other]	0/10 (0%)		1/300 (0.3%)		1/303 (0.3%)
Sudden death	0/10 (0%)		1/300 (0.3%)		1/303 (0.3%)
Visceral edema	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Hepatobiliary disorders
Cholecystitis	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Gallbladder pain	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Immune system disorders
Hypersensitivity	0/10 (0%)		1/300 (0.3%)		2/303 (0.7%)
Infections and infestations
Abdominal infection [with normal or Grade 1-2 ANC]	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Appendicitis [with normal or Grade 1-2 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Appendicitis perforated	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Bladder infection [with normal or Grade 1-2 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Bone infection [with normal or Grade 1-2 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Catheter related infection [with normal or Grade 1-2 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Encephalitis infection [with unknown ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Eye infection [with unknown ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Ileal infection [with normal or Grade 1-2 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Infection [neck, with Grade 3-4 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Infection [other]	0/10 (0%)		2/300 (0.7%)		0/303 (0%)
Infectious colitis [with Grade 3-4 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Infective myositis [with normal or Grade 1-2 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Mucosal infection [with unknown ANC]	0/10 (0%)		2/300 (0.7%)		0/303 (0%)
Opportunistic infection	0/10 (0%)		0/300 (0%)		2/303 (0.7%)
Pancreas infection [with normal or Grade 1-2 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Peripheral nerve infection [with normal or Grade 1-2 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Pneumonia [with Grade 3-4 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Pneumonia [with normal or Grade 1-2 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Pneumonia [with unknown ANC]	0/10 (0%)		3/300 (1%)		2/303 (0.7%)
Rhinitis infective [with unknown ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Sepsis [with Grade 3-4 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Sepsis [with unknown ANC]	0/10 (0%)		2/300 (0.7%)		1/303 (0.3%)
Skin infection [with normal or Grade 1-2 ANC]	0/10 (0%)		1/300 (0.3%)		1/303 (0.3%)
Upper aerodigestive tract infection [with normal or Grade 1-2 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Upper respiratory infection [with unknown ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Urinary tract infection [with Grade 3-4 ANC]	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Urinary tract infection [with normal or Grade 1-2 ANC]	0/10 (0%)		1/300 (0.3%)		1/303 (0.3%)
Urinary tract infection [with unknown ANC]	0/10 (0%)		1/300 (0.3%)		1/303 (0.3%)
Wound infection [with normal or Grade 1-2 ANC]	1/10 (10%)		2/300 (0.7%)		3/303 (1%)
Wound infection [with unknown ANC]	1/10 (10%)		1/300 (0.3%)		1/303 (0.3%)
Injury, poisoning and procedural complications
Fracture	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Intraoperative hepatobiliary injury - Gallbladder	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Small intestinal anastomotic leak	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Vascular access complication	1/10 (10%)		0/300 (0%)		3/303 (1%)
Wound dehiscence	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Wound dehiscence	1/10 (10%)		3/300 (1%)		6/303 (2%)
Investigations
Activated partial thromboplastin time prolonged	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Activated partial thromboplastin time prolonged	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Alanine aminotransferase increased	0/10 (0%)		2/300 (0.7%)		1/303 (0.3%)
Amylase increased	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Aspartate aminotransferase increased	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
CD4 lymphocytes decreased	0/10 (0%)		0/300 (0%)		4/303 (1.3%)
Cardiac troponin T increased	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Creatinine increased	0/10 (0%)		2/300 (0.7%)		3/303 (1%)
Lipase increased	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Neutrophil count decreased	0/10 (0%)		0/300 (0%)		5/303 (1.7%)
Neutrophil count decreased	0/10 (0%)		3/300 (1%)		16/303 (5.3%)
Platelet count decreased	0/10 (0%)		1/300 (0.3%)		10/303 (3.3%)
Platelet count decreased	0/10 (0%)		8/300 (2.7%)		29/303 (9.6%)
Weight gain	0/10 (0%)		0/300 (0%)		2/303 (0.7%)
Weight loss	0/10 (0%)		2/300 (0.7%)		1/303 (0.3%)
Metabolism and nutrition disorders
Anorexia	1/10 (10%)		3/300 (1%)		8/303 (2.6%)
Dehydration	1/10 (10%)		7/300 (2.3%)		8/303 (2.6%)
Hyperglycemia	1/10 (10%)		8/300 (2.7%)		3/303 (1%)
Hyperkalemia	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Hypoalbuminemia	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Hypocalcemia	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Hypoglycemia	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Hypokalemia	0/10 (0%)		0/300 (0%)		2/303 (0.7%)
Hyponatremia	0/10 (0%)		4/300 (1.3%)		2/303 (0.7%)
Musculoskeletal and connective tissue disorders
Back pain	0/10 (0%)		3/300 (1%)		0/303 (0%)
Head soft tissue necrosis	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Joint pain	0/10 (0%)		1/300 (0.3%)		1/303 (0.3%)
Muscle weakness	0/10 (0%)		5/300 (1.7%)		11/303 (3.6%)
Muscle weakness left-sided	0/10 (0%)		2/300 (0.7%)		2/303 (0.7%)
Muscle weakness lower limb	0/10 (0%)		3/300 (1%)		2/303 (0.7%)
Muscle weakness right-sided	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Muscle weakness upper limb	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Osteonecrosis	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Pain in extremity	0/10 (0%)		0/300 (0%)		2/303 (0.7%)
Nervous system disorders
Ataxia	0/10 (0%)		4/300 (1.3%)		6/303 (2%)
Central nervous system necrosis	0/10 (0%)		2/300 (0.7%)		1/303 (0.3%)
Cerebrospinal fluid leakage	0/10 (0%)		1/300 (0.3%)		1/303 (0.3%)
Cognitive disturbance	0/10 (0%)		4/300 (1.3%)		3/303 (1%)
Depressed level of consciousness	0/10 (0%)		3/300 (1%)		3/303 (1%)
Dizziness	0/10 (0%)		0/300 (0%)		3/303 (1%)
Encephalopathy	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Encephalopathy	0/10 (0%)		0/300 (0%)		3/303 (1%)
Extrapyramidal disorder	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Headache	1/10 (10%)		8/300 (2.7%)		4/303 (1.3%)
Hydrocephalus	0/10 (0%)		2/300 (0.7%)		1/303 (0.3%)
Intracranial hemorrhage	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Intracranial hemorrhage	0/10 (0%)		3/300 (1%)		4/303 (1.3%)
Ischemia cerebrovascular	0/10 (0%)		4/300 (1.3%)		7/303 (2.3%)
Leukoencephalopathy	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Memory impairment	0/10 (0%)		5/300 (1.7%)		2/303 (0.7%)
Mental status changes	0/10 (0%)		1/300 (0.3%)		2/303 (0.7%)
Neuralgia	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Neurological disorder NOS	0/10 (0%)		2/300 (0.7%)		1/303 (0.3%)
Peripheral motor neuropathy	0/10 (0%)		5/300 (1.7%)		6/303 (2%)
Peripheral sensory neuropathy	0/10 (0%)		1/300 (0.3%)		2/303 (0.7%)
Seizure	0/10 (0%)		23/300 (7.7%)		20/303 (6.6%)
Speech disorder	0/10 (0%)		8/300 (2.7%)		4/303 (1.3%)
Syncope	0/10 (0%)		2/300 (0.7%)		1/303 (0.3%)
Psychiatric disorders
Agitation	0/10 (0%)		1/300 (0.3%)		1/303 (0.3%)
Anxiety	0/10 (0%)		1/300 (0.3%)		1/303 (0.3%)
Confusion	0/10 (0%)		10/300 (3.3%)		9/303 (3%)
Depression	0/10 (0%)		4/300 (1.3%)		4/303 (1.3%)
Insomnia	0/10 (0%)		0/300 (0%)		2/303 (0.7%)
Psychosis	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Renal and urinary disorders
Hemorrhage urinary tract	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Proteinuria	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Urinary frequency	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Urinary retention	0/10 (0%)		2/300 (0.7%)		1/303 (0.3%)
Urogenital disorder	0/10 (0%)		2/300 (0.7%)		0/303 (0%)
Reproductive system and breast disorders
Vaginal hemorrhage	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Allergic rhinitis	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Atelectasis	0/10 (0%)		1/300 (0.3%)		1/303 (0.3%)
Bronchospasm	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Cough	0/10 (0%)		2/300 (0.7%)		3/303 (1%)
Dyspnea	0/10 (0%)		4/300 (1.3%)		3/303 (1%)
Hypoxia	0/10 (0%)		0/300 (0%)		2/303 (0.7%)
Pneumonitis	0/10 (0%)		2/300 (0.7%)		2/303 (0.7%)
Respiratory disorder	0/10 (0%)		0/300 (0%)		2/303 (0.7%)
Tracheal mucositis	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Skin and subcutaneous tissue disorders
Alopecia	0/10 (0%)		1/300 (0.3%)		1/303 (0.3%)
Decubitus ulcer	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Erythema multiforme	0/10 (0%)		0/300 (0%)		2/303 (0.7%)
Pain of skin	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Pruritus	0/10 (0%)		2/300 (0.7%)		0/303 (0%)
Rash desquamating	0/10 (0%)		1/300 (0.3%)		2/303 (0.7%)
Skin disorder	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Skin ulceration	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Vascular disorders
Hematoma	0/10 (0%)		1/300 (0.3%)		0/303 (0%)
Hypertension	0/10 (0%)		0/300 (0%)		1/303 (0.3%)
Hypotension	0/10 (0%)		2/300 (0.7%)		1/303 (0.3%)
Thrombosis	2/10 (20%)		22/300 (7.3%)		23/303 (7.6%)
Vascular disorder	0/10 (0%)		2/300 (0.7%)		1/303 (0.3%)
Other (Not Including Serious) Adverse Events
	Pre-Randomization TMZ+RT		Randomized Arm 1: TMZ+RT + Placebo		Randomized Arm 2: TMZ+RT + Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/10 (70%)		292/300 (97.3%)		292/303 (96.4%)
Blood and lymphatic system disorders
Blood disorder	0/10 (0%)		20/300 (6.7%)		19/303 (6.3%)
Hemoglobin decreased	2/10 (20%)		124/300 (41.3%)		111/303 (36.6%)
Leukopenia	0/10 (0%)		98/300 (32.7%)		119/303 (39.3%)
Lymphopenia	2/10 (20%)		96/300 (32%)		114/303 (37.6%)
Ear and labyrinth disorders
Hearing loss	1/10 (10%)		18/300 (6%)		20/303 (6.6%)
Tinnitus	1/10 (10%)		16/300 (5.3%)		20/303 (6.6%)
Eye disorders
Eye disorder	0/10 (0%)		25/300 (8.3%)		19/303 (6.3%)
Vision blurred	0/10 (0%)		47/300 (15.7%)		47/303 (15.5%)
Gastrointestinal disorders
Abdominal pain	0/10 (0%)		13/300 (4.3%)		22/303 (7.3%)
Constipation	0/10 (0%)		126/300 (42%)		141/303 (46.5%)
Diarrhea	0/10 (0%)		48/300 (16%)		64/303 (21.1%)
Dry mouth	1/10 (10%)		15/300 (5%)		15/303 (5%)
Dyspepsia	0/10 (0%)		21/300 (7%)		27/303 (8.9%)
Dysphagia	1/10 (10%)		14/300 (4.7%)		15/303 (5%)
Mucositis oral	0/10 (0%)		15/300 (5%)		29/303 (9.6%)
Nausea	2/10 (20%)		165/300 (55%)		184/303 (60.7%)
Vomiting	0/10 (0%)		73/300 (24.3%)		82/303 (27.1%)
General disorders
Chills	0/10 (0%)		10/300 (3.3%)		24/303 (7.9%)
Edema limbs	0/10 (0%)		49/300 (16.3%)		43/303 (14.2%)
Fatigue	3/10 (30%)		238/300 (79.3%)		243/303 (80.2%)
Fever	0/10 (0%)		22/300 (7.3%)		27/303 (8.9%)
Gait abnormal	0/10 (0%)		28/300 (9.3%)		22/303 (7.3%)
Localized edema [head and neck]	0/10 (0%)		21/300 (7%)		16/303 (5.3%)
Pain [other]	0/10 (0%)		20/300 (6.7%)		20/303 (6.6%)
Infections and infestations
Opportunistic infection	1/10 (10%)		2/300 (0.7%)		5/303 (1.7%)
Injury, poisoning and procedural complications
Dermatitis radiation	0/10 (0%)		49/300 (16.3%)		42/303 (13.9%)
Fracture	1/10 (10%)		4/300 (1.3%)		1/303 (0.3%)
Radiation recall reaction (dermatologic)	0/10 (0%)		30/300 (10%)		47/303 (15.5%)
Investigations
Alanine aminotransferase increased	2/10 (20%)		103/300 (34.3%)		93/303 (30.7%)
Alkaline phosphatase increased	0/10 (0%)		30/300 (10%)		30/303 (9.9%)
Aspartate aminotransferase increased	0/10 (0%)		69/300 (23%)		74/303 (24.4%)
CD4 lymphocytes decreased	0/10 (0%)		10/300 (3.3%)		22/303 (7.3%)
Creatinine increased	1/10 (10%)		37/300 (12.3%)		35/303 (11.6%)
Hyperbilirubinemia	0/10 (0%)		19/300 (6.3%)		22/303 (7.3%)
Laboratory test abnormal	0/10 (0%)		39/300 (13%)		39/303 (12.9%)
Neutrophil count decreased	0/10 (0%)		19/300 (6.3%)		34/303 (11.2%)
Neutrophil count decreased	0/10 (0%)		64/300 (21.3%)		83/303 (27.4%)
Platelet count decreased	1/10 (10%)		47/300 (15.7%)		59/303 (19.5%)
Platelet count decreased	0/10 (0%)		135/300 (45%)		171/303 (56.4%)
Weight gain	0/10 (0%)		16/300 (5.3%)		4/303 (1.3%)
Weight loss	1/10 (10%)		39/300 (13%)		55/303 (18.2%)
Metabolism and nutrition disorders
Anorexia	1/10 (10%)		110/300 (36.7%)		127/303 (41.9%)
Dehydration	0/10 (0%)		17/300 (5.7%)		23/303 (7.6%)
Hyperglycemia	2/10 (20%)		114/300 (38%)		121/303 (39.9%)
Hyperkalemia	1/10 (10%)		18/300 (6%)		24/303 (7.9%)
Hypermagnesemia	1/10 (10%)		3/300 (1%)		6/303 (2%)
Hypoalbuminemia	1/10 (10%)		53/300 (17.7%)		53/303 (17.5%)
Hypocalcemia	0/10 (0%)		38/300 (12.7%)		54/303 (17.8%)
Hypoglycemia	0/10 (0%)		14/300 (4.7%)		22/303 (7.3%)
Hypokalemia	0/10 (0%)		43/300 (14.3%)		46/303 (15.2%)
Hyponatremia	2/10 (20%)		54/300 (18%)		73/303 (24.1%)
Musculoskeletal and connective tissue disorders
Back pain	0/10 (0%)		30/300 (10%)		32/303 (10.6%)
Joint pain	0/10 (0%)		33/300 (11%)		50/303 (16.5%)
Muscle weakness	0/10 (0%)		49/300 (16.3%)		58/303 (19.1%)
Muscle weakness left-sided	1/10 (10%)		15/300 (5%)		8/303 (2.6%)
Muscle weakness lower limb	0/10 (0%)		26/300 (8.7%)		24/303 (7.9%)
Musculoskeletal disorder	0/10 (0%)		16/300 (5.3%)		10/303 (3.3%)
Myalgia	0/10 (0%)		18/300 (6%)		29/303 (9.6%)
Pain in extremity	0/10 (0%)		24/300 (8%)		44/303 (14.5%)
Nervous system disorders
Acoustic nerve disorder NOS	1/10 (10%)		4/300 (1.3%)		0/303 (0%)
Ataxia	0/10 (0%)		42/300 (14%)		45/303 (14.9%)
Cognitive disturbance	0/10 (0%)		25/300 (8.3%)		26/303 (8.6%)
Depressed level of consciousness	0/10 (0%)		7/300 (2.3%)		23/303 (7.6%)
Dizziness	0/10 (0%)		77/300 (25.7%)		75/303 (24.8%)
Headache	1/10 (10%)		155/300 (51.7%)		167/303 (55.1%)
Memory impairment	1/10 (10%)		63/300 (21%)		72/303 (23.8%)
Neurological disorder NOS	1/10 (10%)		25/300 (8.3%)		25/303 (8.3%)
Peripheral motor neuropathy	0/10 (0%)		43/300 (14.3%)		41/303 (13.5%)
Peripheral sensory neuropathy	0/10 (0%)		50/300 (16.7%)		47/303 (15.5%)
Seizure	2/10 (20%)		53/300 (17.7%)		61/303 (20.1%)
Speech disorder	0/10 (0%)		56/300 (18.7%)		36/303 (11.9%)
Taste alteration	1/10 (10%)		49/300 (16.3%)		54/303 (17.8%)
Tremor	0/10 (0%)		31/300 (10.3%)		33/303 (10.9%)
Psychiatric disorders
Agitation	0/10 (0%)		27/300 (9%)		19/303 (6.3%)
Anxiety	0/10 (0%)		44/300 (14.7%)		42/303 (13.9%)
Confusion	0/10 (0%)		43/300 (14.3%)		41/303 (13.5%)
Depression	1/10 (10%)		36/300 (12%)		54/303 (17.8%)
Insomnia	0/10 (0%)		74/300 (24.7%)		75/303 (24.8%)
Renal and urinary disorders
Proteinuria	0/10 (0%)		25/300 (8.3%)		28/303 (9.2%)
Urinary frequency	0/10 (0%)		13/300 (4.3%)		24/303 (7.9%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	0/10 (0%)		19/300 (6.3%)		20/303 (6.6%)
Cough	0/10 (0%)		33/300 (11%)		50/303 (16.5%)
Dyspnea	0/10 (0%)		33/300 (11%)		33/303 (10.9%)
Hemorrhage nasal	0/10 (0%)		5/300 (1.7%)		15/303 (5%)
Hemorrhage nasal	0/10 (0%)		16/300 (5.3%)		34/303 (11.2%)
Voice alteration	0/10 (0%)		6/300 (2%)		23/303 (7.6%)
Skin and subcutaneous tissue disorders
Acne	0/10 (0%)		11/300 (3.7%)		17/303 (5.6%)
Alopecia	1/10 (10%)		140/300 (46.7%)		169/303 (55.8%)
Dry skin	0/10 (0%)		17/300 (5.7%)		22/303 (7.3%)
Pruritus	0/10 (0%)		36/300 (12%)		35/303 (11.6%)
Rash desquamating	0/10 (0%)		36/300 (12%)		41/303 (13.5%)
Skin disorder	0/10 (0%)		15/300 (5%)		13/303 (4.3%)
Vascular disorders
Hypertension	1/10 (10%)		39/300 (13%)		67/303 (22.1%)
Thrombosis	2/10 (20%)		24/300 (8%)		18/303 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.