Clinical trial NCT00943826: A Study of Bevacizumab (Avastin®) in Combination With Temozolomide and Radiotherapy in Participants With Newly Diagnosed Glioblastoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Glioblastoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-07-22
Enrollment: 921
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Co-Primary: Progression-free Survival (PFS) as Assessed by Investigator
timeFrame: Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
measure: Co-Primary: Overall Survival (OS)
timeFrame: Randomization until OS Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Secondary outcomes:
measure: PFS as Assessed by an Independent Review Facility
timeFrame: Randomization until PFS Event (Until data cutoff= 31 March 2012 [up to 29.5 months])
measure: Kaplan-Meier (KM) Estimate of One Year Overall Survival
timeFrame: Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
measure: Kaplan-Meier (KM) Estimate of Two Year Overall Survival
timeFrame: Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
measure: 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)
timeFrame: Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
measure: Number of Participants With Non-Serious Adverse Events, Serious Adverse Events and Death
timeFrame: Randomization until study completion (Until data cutoff= 09 Sep 2015 [up to 64 months])
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama At Birmingham; Neuro-Oncology
state: Alabama
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Evanston
country: United States
facility: Oncology-Evanston Nthwest Healthcare Kellogg Cancer Care Ctr
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Cincinnati
country: United States
facility: Hatton Research Institutes
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center and Research Institute
state: Tennessee
city: Charlottesville
country: United States
facility: University of Virgina
state: Virginia
city: Randwick
country: Australia
facility: Prince of Wales Hospital; Department of Medical Oncology
state: New South Wales
city: St Leonards
country: Australia
facility: North Shore Private Hospital; Northern Specialist Centre
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital; Department of Medical Oncology
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess AleXandra Hospital; Department of Medical Oncology
state: Queensland
city: North Adelaide
country: Australia
facility: Calvary North Adelaide; North Adeliade Oncology Centre
state: South Australia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital; Hematology and Medical Oncology
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Bruxelles
country: Belgium
facility: Clin Univ de Bxl Hôpital Erasme
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: AZ Sint Lucas (Sint Lucas)
city: Liège
country: Belgium
facility: CHU Sart-Tilman
city: Roeselare
country: Belgium
facility: AZ Delta (Campus Wilgenstraat)
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre-Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute ; Dept of Medical Oncology
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer Agency, Vancouver Clinic; Dept. of Medical Oncology
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba; Neuro-Oncology
state: Manitoba
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - Juravinski Cancer Centre
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario; Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre; Neuro-Oncology
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital; Pencer Brain Tumour Centre, 18-727
state: Ontario
city: Montreal
country: Canada
facility: Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: McGill University; Montreal Neurological Institute; Oncology
state: Quebec
city: Quebec City
country: Canada
facility: Chuq - Hopital Hotel Dieu de Quebec
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre; Uni of Saskatoon Campus
state: Saskatchewan
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital, Klinik Kirurgi-Kræft, Onkologisk afd.
city: København Ø
country: Denmark
facility: Righospitalet, Hæmatologisk Klinik
city: Odense
country: Denmark
facility: Odense Universitetshospital, Onkologisk Afdeling R
city: Bobigny
country: France
facility: Hopital Avicenne; Rhumatologie
city: Bordeaux
country: France
facility: Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale
city: Bordeaux
country: France
facility: Institut Bergonie; Gastro Enterologie Oncologie
city: Bron
country: France
facility: Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie
city: Clermont Ferrand
country: France
facility: Centre Jean Perrin; Hopital De Jour
city: Clichy
country: France
facility: Hopital Beaujon; Oncologie
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Marseille
country: France
facility: Hopital de La Timone - CHU de Marseille; Service de neuro-oncologie - Hôpital Adultes - 12ème étage
city: Montpellier
country: France
facility: Centre Val Aurelle Paul Lamarque; Medecine B3
city: Nancy
country: France
facility: Hôpital Central; Departement de Neuro-Oncologie
city: Paris
country: France
facility: Hopital Pitié Salpétrière - CHU; Service de neurologie 2 - Mazarin
city: Dresden
country: Germany
facility: Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Neurochirurgie
city: Gießen
country: Germany
facility: Justus-Liebig-Universität Giessen; Neurochirurgische Klinik
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf; Klinik und Poliklinik fur Neurochirurgie
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg; Abteilung Neuroonkologie
city: Ibbenbühren
country: Germany
facility: Ärztehaus Velen
city: Mainz
country: Germany
facility: Klinikum der Johannes Gutenberg Uni Mainz; Studienz. Neurologie, Klinik und Poliklinik Neurologie
city: München
country: Germany
facility: Uni Klinikum München - Großhardern; Med. Klinik U. Poliklinik III - Abt. Onkologie u. Hämatologie
city: Heraklion
country: Greece
facility: Univ General Hosp Heraklion; Medical Oncology
city: Larissa
country: Greece
facility: University Hospital of Larissa; Oncology
city: Thessaloniki
country: Greece
facility: Papageorgiou General Hospital; Medical Oncology
city: Hong Kong
country: Hong Kong
facility: Dr Stephen Yau; Clinical oncology
city: Hong Kong
country: Hong Kong
facility: Hong Kong Sanatorium & Hospital; Comprehensive Oncology Centre
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital; Microbiology Dept.
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház; Neurosurgery
city: Pecs
country: Hungary
facility: Pécsi Tudományegyetem Áok; Onkoterapias Intezet
city: Haifa
country: Israel
facility: Rambam Medical Center; Oncology
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Hospital; Leslie and Michael Gaffin Center for Neuro-Oncology
city: Petach Tikva
country: Israel
facility: Rabin MC; Davidof Center - Oncology Institute
city: Tel Hashomer
country: Israel
facility: Chaim Sheba MC; Pediatric Hematology Oncology
city: Bologna
country: Italy
facility: Ausl Di Bologna-Ospedale Bellaria;U.O. Oncologia Medica
state: Emilia-Romagna
city: Forli
country: Italy
facility: Ospedale Bufalini
state: Emilia-Romagna
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico C. Besta; Neuro-oncologia Sperimentale e Terapia Genica
state: Lombardia
city: Torino
country: Italy
facility: Azienda Ospedaliera Le Molintte di Torino; Dipartimento Di Neurologia - Oncologia
state: Piemonte
city: Terni
country: Italy
facility: Az. Osp. S. Maria; Dept. Di Oncologia Medica
state: Umbria
city: Treviso
country: Italy
facility: Ospedale di Treviso, Universita di Padova; Neurosurgery Dept
state: Veneto
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital; Neurosurgery
city: Ibaraki
country: Japan
facility: Tsukuba University Hospital; Neurology
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital; Neurosurgery
city: Osaka
country: Japan
facility: Kitano Hospital; Neurosurgery
city: Saitama
country: Japan
facility: Saitama Medical University International Medical Center; Clinical and Medical Oncology
city: Tokyo
country: Japan
facility: National Cancer Center Hospital; Neurosurgery
city: Tokyo
country: Japan
facility: Komagome Hospital; Neurosurgery
city: Tokyo
country: Japan
facility: Kyorin University Hospital; Neurosurgery
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital; Neuro Sugery
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hosital; Neuro Sugery
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Centre; Neurosurgery Dept
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center; Medical Oncology
city: Seoul
country: Korea, Republic of
facility: Yonsei University Severance Hospital; Medical Oncology
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center; Neurosurgery Department
city: Amsterdam
country: Netherlands
facility: VU MEDISCH CENTRUM; Dept. of Medical Oncology
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis; Dept of Internal Medicin
city: Utrecht
country: Netherlands
facility: Utrecht University Medical Centre; Dept of Medical Oncology and UPC
city: Auckland
country: New Zealand
facility: Auckland city hospital; Auckland Regional Cancer Centre and Blood Service
city: Christchurch
country: New Zealand
facility: Christchurch Hospital; Dept of Oncology
city: Hamilton
country: New Zealand
facility: Waikato Hospital; Regional Cancer Center
city: Bialystok
country: Poland
facility: Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie; Klinika Neurochirurgii i Neurochirurgii Dzi
city: Coimbra
country: Portugal
facility: IPO de Coimbra; Servico de Oncologia Medica
city: Lisboa
country: Portugal
facility: IPO de Lisboa; Servico de Neurologia
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria; Servico de Oncologia Medica
city: Porto
country: Portugal
facility: Hospital de Sao Joao; Servico de Oncologia
city: Bucharest
country: Romania
facility: Institut Oncologic Prof. Dr. Alexandru Trestioreanu; Departament Radioterapie
city: Cluj-napoca
country: Romania
facility: Institut Oncologic Ion Chiricuta; Departament Radioterapie
city: Targu Mures
country: Romania
facility: Spital Clinic Judetean Mures; Oncologie
city: Moscow
country: Russian Federation
facility: N.N.Burdenko Main Military Clinical Hospital; Oncology Dept
city: Moscow
country: Russian Federation
facility: Russian Research Oncology Center n.a. N.N. Blokhin of the RAMS; Department of Neurosurgery
city: Moscow
country: Russian Federation
facility: Scientific Research Neurosurgery Institute; Dept. of Neurooncology
city: St. Petersburg
country: Russian Federation
facility: Institution of Higher Professional Learning Military; Neurooncology
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial; Servicio de Hematología y Oncología
city: Barcelona
country: Spain
facility: Institut Catala d Oncologia Hospital Duran i Reynals
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz; Servicio de Oncologia
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset; Jubileumskliniken
city: Lund
country: Sweden
facility: Skånes University Hospital, Skånes Department of Onclology
city: Umea
country: Sweden
facility: Norrlands Universitetssjukhus; Cancer Centrum
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset, Onkologkliniken
city: Geneve
country: Switzerland
facility: HUG; Oncologie
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Medical Centre; Neurosurgery
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust; Oncology
city: Newcastle Upon Tyne
country: United Kingdom
facility: Northern Centre for Cancer Care;Oncology
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital; Dept of Haematology
city: Romford
country: United Kingdom
facility: Queen's Hospital; Oncology
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital; Cancer Clinical Trials Centre
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital; Dept of Medical Oncology
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Ctr For Oncolgy
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
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citation: 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.
citation: 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.