A Study of Bevacizumab (Avastin®) in Combination With Temozolomide and Radiotherapy in Participants With Newly Diagnosed Glioblastoma

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Trial of Bevacizumab, Temozolomide and Radiotherapy, Followed by Bevacizumab and Temozolomide Versus Placebo, Temozolomide and Radiotherapy Followed by Placebo and Temozolomide in Patients With Newly Diagnosed Glioblastoma

This 2 arm study investigated the efficacy and safety of the addition of bevacizumab to the current standard of care (multimodality therapy of concurrent radiotherapy plus temozolomide followed by adjuvant temozolomide) as compared to the current standard of care alone. Participants were randomly assigned to either the bevacizumab (10 milligrams per kilogram (mg/kg) intravenously [IV] once every 2 week [q2w]) or the placebo arm, in combination with radiation therapy (total dose 60 Gray [Gy], administered as 2 Gy fractions, 5 days/week) plus temozolomide (75 milligrams per meter squared [mg/m^2] oral administration [po] daily) for 6 weeks. After a 4 week treatment break, participants continued to receive bevacizumab (10 mg/kg IV q2w) or placebo, plus temozolomide (150-200 mg/m^2 po daily on days 1-5 of each 4 week cycle) for 6 cycles of maintenance treatment or until disease progression or unacceptable toxicity, whichever occured first. Following the maintenance phase, bevacizumab (15 mg/kg iv every 3 weeks [q3w]) or placebo monotherapy continued. The time on study treatment was until disease progression.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Bevacizumab; Drug: Temozolomide; Radiation: Radiation therapy; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 921
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital; Department of Medical Oncology
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital; Department of Medical Oncology
    • St Leonards, New South Wales, Australia, 2065
      • North Shore Private Hospital; Northern Specialist Centre
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess AleXandra Hospital; Department of Medical Oncology
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Calvary North Adelaide; North Adeliade Oncology Centre
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Melbourne Hospital; Hematology and Medical Oncology
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Bruxelles, Belgium, 1070
    • Clin Univ de Bxl Hôpital Erasme
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Gent, Belgium, 9000
    • AZ Sint Lucas (Sint Lucas)
  • Liège, Belgium, 4000
    • CHU Sart-Tilman
  • Roeselare, Belgium, 8800
    • AZ Delta (Campus Wilgenstraat)
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre-Calgary
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute ; Dept of Medical Oncology
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Agency, Vancouver Clinic; Dept. of Medical Oncology
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • CancerCare Manitoba; Neuro-Oncology
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Hamilton Health Sciences - Juravinski Cancer Centre
    • Kingston, Ontario, Canada, K7L 5P9
      • Cancer Centre of Southeastern Ontario; Kingston General Hospital
    • London, Ontario, Canada, N6A 4L6
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 1C4
      • Ottawa Hospital Regional Cancer Centre; Neuro-Oncology
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Odette Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital; Pencer Brain Tumour Centre, 18-727
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Hopital Notre-Dame
    • Montreal, Quebec, Canada, H3A 2B4
      • McGill University; Montreal Neurological Institute; Oncology
    • Quebec City, Quebec, Canada, G1R 2J6
      • Chuq - Hopital Hotel Dieu de Quebec
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre; Uni of Saskatoon Campus
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital, Klinik Kirurgi-Kræft, Onkologisk afd.
  • København Ø, Denmark, 2100
    • Righospitalet, Hæmatologisk Klinik
  • Odense, Denmark, 5000
    • Odense Universitetshospital, Onkologisk Afdeling R
• France
  • Bobigny, France, 93009
    • Hopital Avicenne; Rhumatologie
  • Bordeaux, France, 33075
    • Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale
  • Bordeaux, France, 33076
    • Institut Bergonie; Gastro Enterologie Oncologie
  • Bron, France, 69677
    • Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie
  • Clermont Ferrand, France, 63011
    • Centre Jean Perrin; Hopital De Jour
  • Clichy, France, 92118
    • Hopital Beaujon; Oncologie
  • Dijon, France, 21000
    • Centre Georges François Leclerc
  • Marseille, France, 13385
    • Hopital de La Timone - CHU de Marseille; Service de neuro-oncologie - Hôpital Adultes - 12ème étage
  • Montpellier, France, 34298
    • Centre Val Aurelle Paul Lamarque; Medecine B3
  • Nancy, France, 54000
    • Hôpital Central; Departement de Neuro-Oncologie
  • Paris, France, 75651
    • Hopital Pitié Salpétrière - CHU; Service de neurologie 2 - Mazarin
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Neurochirurgie
  • Gießen, Germany, 35392
    • Justus-Liebig-Universität Giessen; Neurochirurgische Klinik
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg-Eppendorf; Klinik und Poliklinik fur Neurochirurgie
  • Heidelberg, Germany, 69120
    • Universitatsklinikum Heidelberg; Abteilung Neuroonkologie
  • Ibbenbühren, Germany, 49479
    • Ärztehaus Velen
  • Mainz, Germany, 55131
    • Klinikum der Johannes Gutenberg Uni Mainz; Studienz. Neurologie, Klinik und Poliklinik Neurologie
  • München, Germany, 81377
    • Uni Klinikum München - Großhardern; Med. Klinik U. Poliklinik III - Abt. Onkologie u. Hämatologie
• Greece
  • Heraklion, Greece, 711 10
    • Univ General Hosp Heraklion; Medical Oncology
  • Larissa, Greece, 41 110
    • University Hospital of Larissa; Oncology
  • Thessaloniki, Greece, 546 29
    • Papageorgiou General Hospital; Medical Oncology
• Hong Kong
  • Hong Kong, Hong Kong
    • Dr Stephen Yau; Clinical oncology
  • Hong Kong, Hong Kong
    • Hong Kong Sanatorium & Hospital; Comprehensive Oncology Centre
  • Hong Kong, Hong Kong
    • Queen Mary Hospital; Microbiology Dept.
• Hungary
  • Budapest, Hungary, H-1134
    • Magyar Honvedseg Egeszsegugyi Kozpont
  • Miskolc, Hungary, 3526
    • Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház; Neurosurgery
  • Pecs, Hungary, 7623
    • Pécsi Tudományegyetem Áok; Onkoterapias Intezet
• Israel
  • Haifa, Israel, 3525408
    • Rambam Medical Center; Oncology
  • Jerusalem, Israel, 91120
    • Hadassah Hebrew University Hospital; Leslie and Michael Gaffin Center for Neuro-Oncology
  • Petach Tikva, Israel, 4941492
    • Rabin MC; Davidof Center - Oncology Institute
  • Tel Hashomer, Israel, 52621
    • Chaim Sheba MC; Pediatric Hematology Oncology
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40139
      • Ausl Di Bologna-Ospedale Bellaria;U.O. Oncologia Medica
    • Forli, Emilia-Romagna, Italy, 47023
      • Ospedale Bufalini
  • Lombardia
    • Milano, Lombardia, Italy, 20133
      • Fondazione IRCCS Istituto Neurologico C. Besta; Neuro-oncologia Sperimentale e Terapia Genica
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • Azienda Ospedaliera Le Molintte di Torino; Dipartimento Di Neurologia - Oncologia
  • Umbria
    • Terni, Umbria, Italy, 05100
      • Az. Osp. S. Maria; Dept. Di Oncologia Medica
  • Veneto
    • Treviso, Veneto, Italy, 31100
      • Ospedale di Treviso, Universita di Padova; Neurosurgery Dept
• Japan
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital; Neurosurgery
  • Ibaraki, Japan, 305-8576
    • Tsukuba University Hospital; Neurology
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital; Neurosurgery
  • Osaka, Japan, 530-8480
    • Kitano Hospital; Neurosurgery
  • Saitama, Japan, 350-1298
    • Saitama Medical University International Medical Center; Clinical and Medical Oncology
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital; Neurosurgery
  • Tokyo, Japan, 113-8677
    • Komagome Hospital; Neurosurgery
  • Tokyo, Japan, 181-8611
    • Kyorin University Hospital; Neurosurgery
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Pusan National University Hospital; Neuro Sugery
  • Daegu, Korea, Republic of, 700-721
    • Kyungpook National University Hosital; Neuro Sugery
  • Goyang-si, Korea, Republic of, 410-769
    • National Cancer Centre; Neurosurgery Dept
  • Jeollanam-do, Korea, Republic of, 58128
    • Chonnam National University Hwasun Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University Severance Hospital; Medical Oncology
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center; Medical Oncology
  • Seoul, Korea, Republic of, 135-170
    • Samsung Medical Center; Neurosurgery Department
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU MEDISCH CENTRUM; Dept. of Medical Oncology
  • Eindhoven, Netherlands, 5623 EJ
    • Catharina Ziekenhuis; Dept of Internal Medicin
  • Utrecht, Netherlands, 3584 CW
    • Utrecht University Medical Centre; Dept of Medical Oncology and UPC
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland city hospital; Auckland Regional Cancer Centre and Blood Service
  • Christchurch, New Zealand
    • Christchurch Hospital; Dept of Oncology
  • Hamilton, New Zealand
    • Waikato Hospital; Regional Cancer Center
• Poland
  • Bialystok, Poland, 15-027
    • Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej
  • Bydgoszcz, Poland, 85-796
    • Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii
  • Lublin, Poland, 20-954
    • Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie; Klinika Neurochirurgii i Neurochirurgii Dzi
• Portugal
  • Coimbra, Portugal, 3000-075
    • IPO de Coimbra; Servico de Oncologia Medica
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria; Servico de Oncologia Medica
  • Lisboa, Portugal, 1099-023
    • IPO de Lisboa; Servico de Neurologia
  • Porto, Portugal, 4200-319
    • Hospital de Sao Joao; Servico de Oncologia
• Romania
  • Bucharest, Romania, 022328
    • Institut Oncologic Prof. Dr. Alexandru Trestioreanu; Departament Radioterapie
  • Cluj-napoca, Romania, 400015
    • Institut Oncologic Ion Chiricuta; Departament Radioterapie
  • Targu Mures, Romania, 540142
    • Spital Clinic Judetean Mures; Oncologie
• Russian Federation
  • Moscow, Russian Federation, 105229
    • N.N.Burdenko Main Military Clinical Hospital; Oncology Dept
  • Moscow, Russian Federation, 115478
    • Russian Research Oncology Center n.a. N.N. Blokhin of the RAMS; Department of Neurosurgery
  • Moscow, Russian Federation, 125047
    • Scientific Research Neurosurgery Institute; Dept. of Neurooncology
  • St. Petersburg, Russian Federation, 194175
    • Institution of Higher Professional Learning Military; Neurooncology
• Spain
  • Barcelona, Spain, 08908
    • Institut Catala d Oncologia Hospital Duran i Reynals
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial; Servicio de Hematología y Oncología
  • Barcelona, Spain, 08916
    • Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Oncologia
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz; Servicio de Oncologia
  • Malaga, Spain, 29010
    • Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
• Sweden
  • Göteborg, Sweden, 413 45
    • Sahlgrenska Universitetssjukhuset; Jubileumskliniken
  • Lund, Sweden, 22185
    • Skånes University Hospital, Skånes Department of Onclology
  • Umea, Sweden, 901 85
    • Norrlands Universitetssjukhus; Cancer Centrum
  • Uppsala, Sweden, 75185
    • Akademiska sjukhuset, Onkologkliniken
• Switzerland
  • Geneve, Switzerland, 1211
    • HUG; Oncologie
• United Kingdom
  • Birmingham, United Kingdom, B15 2TT
    • Queen Elizabeth Medical Centre; Neurosurgery
  • Bristol, United Kingdom, BS2 8ED
    • Bristol Haematology and Oncology Centre
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust; Oncology
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Northern Centre for Cancer Care;Oncology
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital; Dept of Haematology
  • Romford, United Kingdom, RM7 0AG
    • Queen's Hospital; Oncology
  • Sheffield, United Kingdom, S10 2SJ
    • Weston Park Hospital; Cancer Clinical Trials Centre
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital; Dept of Medical Oncology
  • Wirral, United Kingdom, CH63 4JY
    • The Clatterbridge Cancer Ctr For Oncolgy
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama At Birmingham; Neuro-Oncology
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Oncology-Evanston Nthwest Healthcare Kellogg Cancer Care Ctr
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Hatton Research Institutes
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center and Research Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virgina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• newly diagnosed glioblastoma
• World Health Organization (WHO) performance status less than or equal to (<=2)
• stable or decreasing corticosteroid dose within 5 days prior to randomization

Key Exclusion Criteria:

• evidence of recent hemorrhage on postoperative magnetic resonance imaging (MRI) of brain
• any prior chemotherapy or immunotherapy for glioblastomas and low grade astrocytomas
• any prior radiotherapy to brain
• clinically significant cardiovascular disease
• history of greater than or equal to (>=) grade 2 hemoptysis within 1 month prior to randomization
• previous centralized screening for Methylguanine-DNA methyltransferase (MGMT) status for enrollment into a clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bevacizumab + RT + Temozolomide; In the Concurrent Phase participants will receive radiotherapy (RT) in daily fractions of 2 Gy to be given 5 days per week for 6 weeks and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (it may continue for a maximum of 49 days in case of delay to the end of radiation therapy) and bevacizumab 10 mg/kg IV every 2 weeks for 6 weeks. There will be a 4 week treatment break. Participants will then enter the Maintenance Phase where they receive six 28-day cycle of bevacizumab 10 mg/kg IV q2w and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants will then enter the Monotherapy Phase where they will receive bevacizumab 15 mg/kg IV q3w until disease progression/unacceptable toxicity.	Drug: Bevacizumab; 10 mg/kg intravenously q2w in the Concurrent and Maintenance Phases. 15 mg/kg intravenously q3w in the Monotherapy Phase.; Other Names: Avastin; Drug: Temozolomide; 75 mg/m^2 once daily for 6 weeks, followed by 150-200 mg/m^2 once daily on days 1-5 of six 4 week cycles.; Radiation: Radiation therapy; 30 fractions of 2 Gy delivered on days 1-5 per week for 6 weeks.
Placebo Comparator: Placebo + RT + Temozolomide; In the Concurrent Phase participants will receive radiotherapy in daily fractions of 2 Gy to be given 5 days per week for 6 weeks and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (it may continue for a maximum of 49 days in case of delay to the end of radiation therapy) and placebo IV every 2 weeks for 6 weeks. There will be a 4 week treatment break. Participants will then enter the Maintenance Phase where they will receive six 28-day cycle of placebo IV q2w and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants will then enter the Monotherapy Phase where they will receive placebo IV q3w until disease progression/unacceptable toxicity.	Drug: Temozolomide; 75 mg/m^2 once daily for 6 weeks, followed by 150-200 mg/m^2 once daily on days 1-5 of six 4 week cycles.; Radiation: Radiation therapy; 30 fractions of 2 Gy delivered on days 1-5 per week for 6 weeks.; Drug: Placebo; Intravenously q2w in the Concurrent and Maintenance Phases and q3w in the Monotherapy Phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Co-Primary: Progression-free Survival (PFS) as Assessed by Investigator	PFS is defined as time from randomization to disease progression (PD) or death. PD was assessed using adapted Macdonald response criteria (modified World Health Organization [WHO] criteria) based on 3 components: radiological tumor assessments using Magnetic Resonance Imaging [MRI] scans,neurological assessment and changes in corticosteroid use. PD is assessed as greater than or equal to(>=) 25% increase in sum of products of the longest diameters of all index lesions (enhancing,measurable) compared with the smallest recorded sum (nadir); or unequivocal PD of existing non-index lesions (non-enhancing and enhancing,non-measurable); or unequivocal appearance of new lesions); or neurological worsening (if corticosteroid dose is stable or increased) compared to neurological evaluation at previous disease assessment with no need for a confirmatory scan. Participants without a PFS event were censored at last disease assessment.	Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
Co-Primary: Overall Survival (OS)	Overall Survival was defined as the time from randomization to death due to any cause.	Randomization until OS Event (Until data cutoff= 28 February 2013 [up to 42.2 months])

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS as Assessed by an Independent Review Facility	An Independent Review Facility reviewed the MRI scans used by investigator to evaluate radiological tumor response. PFS is defined as time from randomization to PD or death. PD was assessed using adapted Macdonald response (modified WHO) criteria based on 3 components: radiological tumor assessments using MRI scans, neurological assessment and changes in corticosteroid use. PD is assessed as >=25% increase in sum of products of the longest diameters of all index lesions (enhancing, measurable) compared with the smallest recorded sum (nadir); or unequivocal PD of existing non-index lesions (non-enhancing and enhancing, non-measurable); or unequivocal appearance of new lesions); or neurological worsening (if corticosteroid dose is stable or increased) compared to neurological evaluation at previous disease assessment with no need for a confirmatory scan. Participants without a PFS event were censored at last disease assessment.	Randomization until PFS Event (Until data cutoff= 31 March 2012 [up to 29.5 months])
Kaplan-Meier (KM) Estimate of One Year Overall Survival	KM estimate of one year overall survival (probability to survive for at least 1 year) was reported. Corresponding 95% confidence interval (CI) was calculated using Greenwood's formula.	Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Kaplan-Meier (KM) Estimate of Two Year Overall Survival	KM estimate of two year overall survival was reported (probability to survive for at least 2 years). Corresponding 95% CI was calculated using Greenwood's formula.	Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
PFS in Participants With Stable/Improved Health Related Quality of Life (HRQoL) Based on European Organization for Research & Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30)(EORTC QLQ-C30) & EORTC QLQ Brain Neoplasm 20 (BN20)	EORTC QLQ-C30: 30 items; 5 functional scales; 9 symptom scales; & global health status. Most questions used 4-point scale (1:Not at all, 4:Very much), 2 questions used 7-point scale (1:very poor, 7:Excellent). EORTC QLQ-BN20: 20 items rated on a 4 point scale (1:not at all, 4:very much). EORTC QLQ-C30 and BN20 scores were transformed to a 0-100 scale, higher score=better functioning/global health (C30) or more severe symptoms (BN20). Stable HRQoL: change from baseline (BL) within 10 points. Improved HRQoL: an increase from BL >/=10 points for functioning/global health status, & decrease of >/=10 points for symptoms. PFS is reported for participants with Stable/Improved global health; physical, social functioning (C30); motor dysfunction & communication deficit (BN20). PFS: randomization to PD or death. PD: >=25% increase in sum of products of longest diameters of index lesions; or progression of existing non-index lesions; or appearance of new lesions; or neurological worsening.	Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
Number of Participants With Non-Serious Adverse Events, Serious Adverse Events and Death	An adverse event (AE) was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as AE.A serious adverse event (SAE) is any experience that suggests a significant hazard,contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. Non-serious adverse events (Non-SAEs) included all AEs except SAEs (non-SAEs = all AEs - SAEs). Nine participants randomized to the Placebo+RT+Temozolomide arm incorrectly received at least 1 dose of bevacizumab and were added to the Bevacizumab+RT+Temozolomide arm for Safety.	Randomization until study completion (Until data cutoff= 09 Sep 2015 [up to 64 months])

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Hagiwara A, Schlossman J, Shabani S, Raymond C, Tatekawa H, Abrey LE, Garcia J, Chinot O, Saran F, Nishikawa R, Henriksson R, Mason WP, Wick W, Cloughesy TF, Ellingson BM. Incidence, molecular characteristics, and imaging features of "clinically-defined pseudoprogression" in newly diagnosed glioblastoma treated with chemoradiation. J Neurooncol. 2022 Sep;159(3):509-518. doi: 10.1007/s11060-022-04088-3. Epub 2022 Jul 17.
• Jiguet-Jiglaire C, Boissonneau S, Denicolai E, Hein V, Lasseur R, Garcia J, Romain S, Appay R, Graillon T, Mason W, Carpentier AF, Brandes AA, Ouafik L', Wick W, Baaziz A, Gigan JP, Arguello RJ, Figarella-Branger D, Chinot O, Tabouret E. Plasmatic MMP9 released from tumor-infiltrating neutrophils is predictive for bevacizumab efficacy in glioblastoma patients: an AVAglio ancillary study. Acta Neuropathol Commun. 2022 Jan 3;10(1):1. doi: 10.1186/s40478-021-01305-4.
• Chinot OL, Nishikawa R, Mason W, Henriksson R, Saran F, Cloughesy T, Garcia J, Revil C, Abrey L, Wick W. Upfront bevacizumab may extend survival for glioblastoma patients who do not receive second-line therapy: an exploratory analysis of AVAglio. Neuro Oncol. 2016 Sep;18(9):1313-8. doi: 10.1093/neuonc/now046. Epub 2016 Mar 22.
• Saran F, Chinot OL, Henriksson R, Mason W, Wick W, Cloughesy T, Dhar S, Pozzi E, Garcia J, Nishikawa R. Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy. Neuro Oncol. 2016 Jul;18(7):991-1001. doi: 10.1093/neuonc/nov300. Epub 2016 Jan 24.
• Taphoorn MJ, Henriksson R, Bottomley A, Cloughesy T, Wick W, Mason WP, Saran F, Nishikawa R, Hilton M, Theodore-Oklota C, Ravelo A, Chinot OL. Health-Related Quality of Life in a Randomized Phase III Study of Bevacizumab, Temozolomide, and Radiotherapy in Newly Diagnosed Glioblastoma. J Clin Oncol. 2015 Jul 1;33(19):2166-75. doi: 10.1200/JCO.2014.60.3217. Epub 2015 May 26.
• Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):709-22. doi: 10.1056/NEJMoa1308345.
• Chinot OL, Macdonald DR, Abrey LE, Zahlmann G, Kerloeguen Y, Cloughesy TF. Response assessment criteria for glioblastoma: practical adaptation and implementation in clinical trials of antiangiogenic therapy. Curr Neurol Neurosci Rep. 2013 May;13(5):347. doi: 10.1007/s11910-013-0347-2.

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2009
• Primary Completion (Actual): February 28, 2013
• Study Completion (Actual): September 9, 2015

Study Registration Dates

• First Submitted: July 17, 2009
• First Submitted That Met QC Criteria: July 21, 2009
• First Posted (Estimate): July 22, 2009

Study Record Updates

• Last Update Posted (Actual): September 25, 2017
• Last Update Submitted That Met QC Criteria: August 25, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Temozolomide; Bevacizumab
• Other Study ID Numbers: BO21990; 2008-006146-26 (EudraCT Number)