GlioblastomaPhase 3NCT00943826
A Study of Bevacizumab (Avastin®) in Combination With Temozolomide and Radiotherapy in Participants With Newly Diagnosed Glioblastoma
A Phase 3 study testing Bevacizumab, Temozolomide and Radiation therapy in people with Glioblastoma, run by Hoffmann-La Roche at 133 sites in 24 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Bevacizumab, Temozolomide and Radiation therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 921 participants
- Where
- 133 sitesin 24 countries
- Study dates
- 29 Jun 2009to 9 Sep 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
133 sites in 24 countries.
133 sites in 24 countries
Canada14 sites
Tom Baker Cancer Centre-Calgary
Calgary, Alberta, T2N 4N2
Cross Cancer Institute ; Dept of Medical Oncology
Edmonton, Alberta, T6G 1Z2
Hamilton Health Sciences - Juravinski Cancer Centre
Hamilton, Ontario, L8V 5C2
Cancer Centre of Southeastern Ontario; Kingston General Hospital
Kingston, Ontario, K7L 5P9
London Health Sciences Centre
London, Ontario, N6A 4L6
Hopital Notre-Dame
Montreal, Quebec, H2L 4M1
McGill University; Montreal Neurological Institute; Oncology
Montreal, Quebec, H3A 2B4
Ottawa Hospital Regional Cancer Centre; Neuro-Oncology
Ottawa, Ontario, K1H 1C4
Chuq - Hopital Hotel Dieu de Quebec
Québec, Quebec, G1R 2J6
Saskatoon Cancer Centre; Uni of Saskatoon Campus
Saskatoon, Saskatchewan, S7N 4H4
Sunnybrook Odette Cancer Centre
Toronto, Ontario, M4N 3M5
Princess Margaret Hospital; Pencer Brain Tumour Centre, 18-727
Toronto, Ontario, M5G 2M9
BC Cancer Agency, Vancouver Clinic; Dept. of Medical Oncology
Vancouver, British Columbia, V5Z 4E6
CancerCare Manitoba; Neuro-Oncology
Winnipeg, Manitoba, R2H 2A6
France11 sites
Hopital Avicenne; Rhumatologie
Bobigny, 93009
Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale
Bordeaux, 33075
Institut Bergonie; Gastro Enterologie Oncologie
Bordeaux, 33076
Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie
Bron, 69677
Centre Jean Perrin; Hopital De Jour
Clermont-Ferrand, 63011
Hopital Beaujon; Oncologie
Clichy, 92118
Centre Georges François Leclerc
Dijon, 21000
Hopital de La Timone - CHU de Marseille; Service de neuro-oncologie - Hôpital Adultes - 12ème étage
Marseille, 13385
Centre Val Aurelle Paul Lamarque; Medecine B3
Montpellier, 34298
Hôpital Central; Departement de Neuro-Oncologie
Nancy, 54000
Hopital Pitié Salpétrière - CHU; Service de neurologie 2 - Mazarin
Paris, 75651
United States9 sites
University of Colorado
Aurora, Colorado, 80045
University of Alabama At Birmingham; Neuro-Oncology
Birmingham, Alabama, 35294
University of Virgina
Charlottesville, Virginia, 22908
Hatton Research Institutes
Cincinnati, Ohio, 45220
Henry Ford Health System
Detroit, Michigan, 48202
Oncology-Evanston Nthwest Healthcare Kellogg Cancer Care Ctr
Evanston, Illinois, 60201
UCLA
Los Angeles, California, 90095
Sarah Cannon Cancer Center and Research Institute
Nashville, Tennessee, 37203
Moffitt Cancer Center
Tampa, Florida, 33612
United Kingdom9 sites
Queen Elizabeth Medical Centre; Neurosurgery
Birmingham, B15 2TT
Bristol Haematology and Oncology Centre
Bristol, BS2 8ED
The Royal Marsden NHS Foundation Trust; Oncology
London, SW3 6JJ
The Clatterbridge Cancer Ctr For Oncolgy
Metropolitan Borough of Wirral, CH63 4JY
Northern Centre for Cancer Care;Oncology
Newcastle upon Tyne, NE7 7DN
Nottingham City Hospital; Dept of Haematology
Nottingham, NG5 1PB
Queen's Hospital; Oncology
Romford, RM7 0AG
Weston Park Hospital; Cancer Clinical Trials Centre
Sheffield, S10 2SJ
Royal Marsden Hospital; Dept of Medical Oncology
Sutton, SM2 5PT
Japan8 sites
Hiroshima University Hospital; Neurosurgery
Hiroshima, 734-8551
Tsukuba University Hospital; Neurology
Ibaraki, 305-8576
Kumamoto University Hospital; Neurosurgery
Kumamoto, 860-8556
Kitano Hospital; Neurosurgery
Osaka, 530-8480
Saitama Medical University International Medical Center; Clinical and Medical Oncology
Saitama, 350-1298
National Cancer Center Hospital; Neurosurgery
Tokyo, 104-0045
Komagome Hospital; Neurosurgery
Tokyo, 113-8677
Kyorin University Hospital; Neurosurgery
Tokyo, 181-8611
South Korea8 sites
Pusan National University Hospital; Neuro Sugery
Busan, 602-739
Kyungpook National University Hosital; Neuro Sugery
Daegu, 700-721
National Cancer Centre; Neurosurgery Dept
Goyang-si, 410-769
Chonnam National University Hwasun Hospital
Jeollanam-do, 58128
Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
Seoul, 03080
Asan Medical Center; Medical Oncology
Seoul, 05505
Yonsei University Severance Hospital; Medical Oncology
Seoul, 120-752
Samsung Medical Center; Neurosurgery Department
Seoul, 135-170
Australia7 sites
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009
Calvary North Adelaide; North Adeliade Oncology Centre
North Adelaide, South Australia, 5006
Royal Melbourne Hospital; Hematology and Medical Oncology
Parkville, Victoria, 3052
Prince of Wales Hospital; Department of Medical Oncology
Randwick, New South Wales, 2031
North Shore Private Hospital; Northern Specialist Centre
St Leonards, New South Wales, 2065
Royal North Shore Hospital; Department of Medical Oncology
St Leonards, New South Wales, 2065
Princess AleXandra Hospital; Department of Medical Oncology
Woolloongabba, Queensland, 4102
Germany7 sites
Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Neurochirurgie
Dresden, 01307
Justus-Liebig-Universität Giessen; Neurochirurgische Klinik
Giessen, 35392
Universitatsklinikum Hamburg-Eppendorf; Klinik und Poliklinik fur Neurochirurgie
Hamburg, 20246
Universitatsklinikum Heidelberg; Abteilung Neuroonkologie
Heidelberg, 69120
Ärztehaus Velen
Ibbenbühren, 49479
Klinikum der Johannes Gutenberg Uni Mainz; Studienz. Neurologie, Klinik und Poliklinik Neurologie
Mainz, 55131
Uni Klinikum München - Großhardern; Med. Klinik U. Poliklinik III - Abt. Onkologie u. Hämatologie
München, 81377
Spain7 sites
Hospital Clínic i Provincial; Servicio de Hematología y Oncología
Barcelona, 08036
Institut Catala d Oncologia Hospital Duran i Reynals
Barcelona, 08908
Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
Barcelona, 08916
Hospital Ramon y Cajal; Servicio de Oncologia
Madrid, 28034
Hospital Universitario La Paz; Servicio de Oncologia
Madrid, 28046
Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
Málaga, 29010
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
Valencia, 46010
Belgium6 sites
Clin Univ de Bxl Hôpital Erasme
Brussels, 1070
Cliniques Universitaires St-Luc
Brussels, 1200
UZ Antwerpen
Edegem, 2650
AZ Sint Lucas (Sint Lucas)
Ghent, 9000
CHU Sart-Tilman
Liège, 4000
AZ Delta (Campus Wilgenstraat)
Roeselare, 8800
Italy6 sites
Ausl Di Bologna-Ospedale Bellaria;U.O. Oncologia Medica
Bologna, Emilia-Romagna, 40139
Ospedale Bufalini
Forlì, Emilia-Romagna, 47023
Fondazione IRCCS Istituto Neurologico C. Besta; Neuro-oncologia Sperimentale e Terapia Genica
Milan, Lombardy, 20133
Az. Osp. S. Maria; Dept. Di Oncologia Medica
Terni, Umbria, 05100
Ospedale di Treviso, Universita di Padova; Neurosurgery Dept
Treviso, Veneto, 31100
Azienda Ospedaliera Le Molintte di Torino; Dipartimento Di Neurologia - Oncologia
Turin, Piedmont, 10126
Israel4 sites
Rambam Medical Center; Oncology
Haifa, 3525408
Hadassah Hebrew University Hospital; Leslie and Michael Gaffin Center for Neuro-Oncology
Jerusalem, 91120
Rabin MC; Davidof Center - Oncology Institute
Petah Tikva, 4941492
Chaim Sheba MC; Pediatric Hematology Oncology
Tel HaShomer, 52621
Portugal4 sites
IPO de Coimbra; Servico de Oncologia Medica
Coimbra, 3000-075
IPO de Lisboa; Servico de Neurologia
Lisbon, 1099-023
Hospital de Santa Maria; Servico de Oncologia Medica
Lisbon, 1649-035
Hospital de Sao Joao; Servico de Oncologia
Porto, 4200-319
Russia4 sites
N.N.Burdenko Main Military Clinical Hospital; Oncology Dept
Moscow, 105229
Russian Research Oncology Center n.a. N.N. Blokhin of the RAMS; Department of Neurosurgery
Moscow, 115478
Scientific Research Neurosurgery Institute; Dept. of Neurooncology
Moscow, 125047
Institution of Higher Professional Learning Military; Neurooncology
Saint Petersburg, 194175
Sweden4 sites
Sahlgrenska Universitetssjukhuset; Jubileumskliniken
Gothenburg, 413 45
Skånes University Hospital, Skånes Department of Onclology
Lund, 22185
Norrlands Universitetssjukhus; Cancer Centrum
Umeå, 901 85
Akademiska sjukhuset, Onkologkliniken
Uppsala, 75185
Denmark3 sites
Aalborg Universitetshospital, Klinik Kirurgi-Kræft, Onkologisk afd.
Aalborg, 9000
Righospitalet, Hæmatologisk Klinik
København Ø, 2100
Odense Universitetshospital, Onkologisk Afdeling R
Odense, 5000
Greece3 sites
Univ General Hosp Heraklion; Medical Oncology
Heraklion, 711 10
University Hospital of Larissa; Oncology
Larissa, 41 110
Papageorgiou General Hospital; Medical Oncology
Thessaloniki, 546 29
Hong Kong3 sites
Dr Stephen Yau; Clinical oncology
Hong Kong
Hong Kong Sanatorium & Hospital; Comprehensive Oncology Centre
Hong Kong
Queen Mary Hospital; Microbiology Dept.
Hong Kong
Hungary3 sites
Magyar Honvedseg Egeszsegugyi Kozpont
Budapest, H-1134
Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház; Neurosurgery
Miskolc, 3526
Pécsi Tudományegyetem Áok; Onkoterapias Intezet
Pécs, 7623
Netherlands3 sites
VU MEDISCH CENTRUM; Dept. of Medical Oncology
Amsterdam, 1081 HV
Catharina Ziekenhuis; Dept of Internal Medicin
Eindhoven, 5623 EJ
Utrecht University Medical Centre; Dept of Medical Oncology and UPC
Utrecht, 3584 CW
New Zealand3 sites
Auckland city hospital; Auckland Regional Cancer Centre and Blood Service
Auckland, 1023
Christchurch Hospital; Dept of Oncology
Christchurch
Waikato Hospital; Regional Cancer Center
Hamilton
Poland3 sites
Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej
Bialystok, 15-027
Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii
Bydgoszcz, 85-796
Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie; Klinika Neurochirurgii i Neurochirurgii Dzi
Lublin, 20-954
Romania3 sites
Institut Oncologic Prof. Dr. Alexandru Trestioreanu; Departament Radioterapie
Bucharest, 022328
Institut Oncologic Ion Chiricuta; Departament Radioterapie
Cluj-Napoca, 400015
Spital Clinic Judetean Mures; Oncologie
Târgu Mureş, 540142
About this study
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
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.
- Conditions
- Glioblastoma
- Being tested
- Bevacizumab, Temozolomide, Radiation therapy, Placebo
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
10 mg/kg intravenously q2w in the Concurrent and Maintenance Phases. 15 mg/kg intravenously q3w in the Monotherapy Phase.
TemozolomideDrug
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 therapyRadiation
30 fractions of 2 Gy delivered on days 1-5 per week for 6 weeks.
PlaceboDrug
Intravenously q2w in the Concurrent and Maintenance Phases and q3w in the Monotherapy Phase.
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab + RT + Temozolomide | Experimental | 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. Receives: Drug: Bevacizumab; Drug: Temozolomide; Radiation: Radiation therapy |
| Placebo + RT + Temozolomide | Placebo comparator | 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. Receives: Drug: Temozolomide; Radiation: Radiation therapy; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Randomization until OS Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Randomization until study completion (Until data cutoff= 09 Sep 2015 [up to 64 months])
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2009 (estimated)
- Study start29 Jun 2009
- Primary completion28 Feb 2013
- Study completion9 Sep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 921 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00943826
- Sponsor's protocol ID
- BO21990
- Other IDs
- 2008-006146-26, 2008
- Status last verified
- Aug 2017
- First submitted
- 17 Jul 2009
- Last updated
- 25 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Seliger C, Oppong FB, Lefranc F, Chinot O, Stupp R, Nabors B, Gorlia T, Weller M; EORTC Brain Tumor Group. Association of antidepressant drug use with outcome of patients with glioblastoma. Int J Cancer. 2023 Apr 1;152(7):1348-1359. doi: 10.1002/ijc.34344. Epub 2022 Nov 17.
PubMed 36346112Hagiwara 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.
PubMed 35842871Jiguet-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.
PubMed 34980260Chinot 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.
PubMed 27006178Saran 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.
PubMed 26809751Taphoorn 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.
PubMed 26014298Chinot 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.
PubMed 24552318Chinot 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.
PubMed 23529375
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00943826
- Acronym / sponsor ID
- BO21990
- Conditions
- Glioblastoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 921 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 29 Jun 2009 (actual)
- Primary completion
- 28 Feb 2013 (actual)
- Study completion
- 9 Sep 2015 (actual)
- First posted
- 22 Jul 2009 (estimated)
- Results
- Posted 20 May 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab + RT + Temozolomide | Experimental | Drug: Bevacizumab, Drug: Temozolomide, Radiation: Radiation therapyIn 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. |
| Placebo + RT + Temozolomide | Placebo comparator | Drug: Temozolomide, Radiation: Radiation therapy, Drug: PlaceboIn 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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 (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: Avastin10 mg/kg intravenously q2w in the Concurrent and Maintenance Phases. 15 mg/kg intravenously q3w in the Monotherapy Phase. | Drug | Bevacizumab + RT + Temozolomide |
| Temozolomide75 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. | Drug | Bevacizumab + RT + Temozolomide, Placebo + RT + Temozolomide |
| Radiation therapy30 fractions of 2 Gy delivered on days 1-5 per week for 6 weeks. | Radiation | Bevacizumab + RT + Temozolomide, Placebo + RT + Temozolomide |
| PlaceboIntravenously q2w in the Concurrent and Maintenance Phases and q3w in the Monotherapy Phase. | Drug | Placebo + RT + Temozolomide |
Primary outcome
Co-Primary: Progression-free Survival (PFS) as Assessed by Investigator
Time frame: Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
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.
Co-Primary: Overall Survival (OS)
Time frame: Randomization until OS Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Overall Survival was defined as the time from randomization to death due to any cause.
5 secondary outcomes
PFS as Assessed by an Independent Review Facility
Time frame: Randomization until PFS Event (Until data cutoff= 31 March 2012 [up to 29.5 months])
Kaplan-Meier (KM) Estimate of One Year Overall Survival
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: Randomization until study completion (Until data cutoff= 09 Sep 2015 [up to 64 months])
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36346112Seliger C, Oppong FB, Lefranc F, Chinot O, Stupp R, Nabors B, Gorlia T, Weller M; EORTC Brain Tumor Group. Association of antidepressant drug use with outcome of patients with glioblastoma. Int J Cancer. 2023 Apr 1;152(7):1348-1359. doi: 10.1002/ijc.34344. Epub 2022 Nov 17.
- Derived from this study: PubMed 35842871Hagiwara 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.
- Derived from this study: PubMed 34980260Jiguet-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.
- Derived from this study: PubMed 27006178Chinot 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.
- Derived from this study: PubMed 26809751Saran 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.
- Derived from this study: PubMed 26014298Taphoorn 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.
- Derived from this study: PubMed 24552318Chinot 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.
- Derived from this study: PubMed 23529375Chinot 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
133 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bevacizumab, Temozolomide and Radiation therapy in people with Glioblastoma, run by Hoffmann-La Roche at 133 sites in 24 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 133 sites in Canada, France, United States, United Kingdom, Japan and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Co-Primary: Progression-free Survival (PFS) as Assessed by Investigator (time frame: Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00943826, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2017.