TriangleNCT00943826 · CITED IN SOURCE DOCUMENTS
A Study of Bevacizumab (Avastin®) in Combination With Temozolomide and Radiotherapy in Participants With Newly Diagnosed Glioblastoma
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2017-09-25
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Co-Primary: Progression-free Survival (PFS) as Assessed by Investigator
Co-Primary: Overall Survival (OS)
PFS as Assessed by an Independent Review Facility
Kaplan-Meier (KM) Estimate of One Year Overall Survival
Kaplan-Meier (KM) Estimate of Two Year Overall Survival
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)
Number of Participants With Non-Serious Adverse Events, Serious Adverse Events and Death
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 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.
- intervention Names
- Drug: Bevacizumab
- Drug: Temozolomide
- Radiation: Radiation therapy
- label
- Bevacizumab + RT + Temozolomide
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Temozolomide
- Radiation: Radiation therapy
- Drug: Placebo
- label
- Placebo + RT + Temozolomide
- type
- PLACEBO_COMPARATOR
- interventions
- arm Group Labels
- Bevacizumab + RT + Temozolomide
- description
- 10 mg/kg intravenously q2w in the Concurrent and Maintenance Phases. 15 mg/kg intravenously q3w in the Monotherapy Phase.
- name
- Bevacizumab
- other Names
- Avastin
- type
- DRUG
- arm Group Labels
- Bevacizumab + RT + Temozolomide
- Placebo + RT + Temozolomide
- description
- 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.
- name
- Temozolomide
- type
- DRUG
- arm Group Labels
- Bevacizumab + RT + Temozolomide
- Placebo + RT + Temozolomide
- description
- 30 fractions of 2 Gy delivered on days 1-5 per week for 6 weeks.
- name
- Radiation therapy
- type
- RADIATION
- arm Group Labels
- Placebo + RT + Temozolomide
- description
- Intravenously q2w in the Concurrent and Maintenance Phases and q3w in the Monotherapy Phase.
- name
- Placebo
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- QUADRUPLE
- who Masked
- PARTICIPANT
- CARE_PROVIDER
- INVESTIGATOR
- OUTCOMES_ASSESSOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 921
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- 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)
- description
- Overall Survival was defined as the time from randomization to death due to any cause.
- measure
- Co-Primary: Overall Survival (OS)
- time Frame
- Randomization until OS Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
- secondary Outcomes
- description
- 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.
- measure
- 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])
- description
- 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.
- measure
- 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])
- description
- 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.
- measure
- 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])
- description
- 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.
- 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)
- time Frame
- Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
- description
- 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.
- measure
- 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])
Full study description
- 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.
Source references
- references
- citation
- 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.
- pmid
- 36346112
- type
- DERIVED
- citation
- 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.
- pmid
- 35842871
- type
- DERIVED
- citation
- 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.
- pmid
- 34980260
- type
- DERIVED
- citation
- 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.
- pmid
- 27006178
- type
- DERIVED
- citation
- 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.
- pmid
- 26809751
- type
- DERIVED
- citation
- 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.
- pmid
- 26014298
- type
- DERIVED
- 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.
- pmid
- 24552318
- type
- DERIVED
- 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.
- pmid
- 23529375
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- newly diagnosed glioblastoma were reported: <a href="/clinicaltrials/NCT00884741">RTOG 0825</a> (NCT00884741) and the Roche-sponsored <a href="/clinicaltrials/NCT00943826">AVAglio</a> (NCT00943826).[<a href="#cit/section_4.17">17</a>,<a href="#cit/section_4.18">18</a>][<a href="/Common/PopUps/popDefinition.aspx?id=810017&ver
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- March 28, 2025
Preserved source evidence · Not medical advice