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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
921
10 mg/kg intravenously q2w in the Concurrent and Maintenance Phases. 15 mg/kg intravenously q3w in the Monotherapy Phase.
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.
30 fractions of 2 Gy delivered on days 1-5 per week for 6 weeks.
Intravenously q2w in the Concurrent and Maintenance Phases and q3w in the Monotherapy Phase.
University of Alabama At Birmingham; Neuro-Oncology
Birmingham, Alabama, United States
UCLA
Los Angeles, California, United States
University of Colorado
Aurora, Colorado, United States
Moffitt Cancer Center
Tampa, Florida, United States
Oncology-Evanston Nthwest Healthcare Kellogg Cancer Care Ctr
Evanston, Illinois, United States
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.
Time frame: 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.
Time frame: Randomization until OS Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
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.
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
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.
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
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.
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)
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.
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
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.
Time frame: Randomization until study completion (Until data cutoff= 09 Sep 2015 [up to 64 months])
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Henry Ford Health System
Detroit, Michigan, United States
Hatton Research Institutes
Cincinnati, Ohio, United States
Sarah Cannon Cancer Center and Research Institute
Nashville, Tennessee, United States
University of Virgina
Charlottesville, Virginia, United States
Prince of Wales Hospital; Department of Medical Oncology
Randwick, New South Wales, Australia
...and 123 more locations