Trial Outcomes & Findings for Bevacizumab, Temozolomide, and External Beam Radiation Therapy as First-Line Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma (NCT NCT01013285)
NCT ID: NCT01013285
Last Updated: 2020-09-21
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
70 participants
Primary outcome timeframe
2 years
Results posted on
2020-09-21
Participant Flow
Seventy patients with newly diagnosed Glioblastoma Multiforme were enrolled between August 2006 and November 2008 from two participating sites, comprised of University of California, Los Angeles (UCLA) and Kaiser Permanente Los Angeles.
Control cohort was derived from University of California, Los Angeles/Kaiser Permanente Los Angeles patients treated with first-line radiation therapy and temozolomide who had mostly received bevacizumab at recurrence.
Participant milestones
| Measure |
Treatment Arm
bevacizumab
temozolomide
external beam radiation therapy
|
Historical Control UCLA/KPLA
A University of California, Los Angeles/Kaiser Permanente Los Angeles(KPLA) control cohort of newly diagnosed patients treated with first-line radiation therapy and temozolomide who had mostly received bevacizumab at recurrence was derived for comparison.
|
|---|---|---|
|
Overall Study
STARTED
|
70
|
110
|
|
Overall Study
COMPLETED
|
22
|
21
|
|
Overall Study
NOT COMPLETED
|
48
|
89
|
Reasons for withdrawal
| Measure |
Treatment Arm
bevacizumab
temozolomide
external beam radiation therapy
|
Historical Control UCLA/KPLA
A University of California, Los Angeles/Kaiser Permanente Los Angeles(KPLA) control cohort of newly diagnosed patients treated with first-line radiation therapy and temozolomide who had mostly received bevacizumab at recurrence was derived for comparison.
|
|---|---|---|
|
Overall Study
Death
|
48
|
89
|
Baseline Characteristics
Bevacizumab, Temozolomide, and External Beam Radiation Therapy as First-Line Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma
Baseline characteristics by cohort
| Measure |
Treatment Arm
n=70 Participants
bevacizumab
temozolomide
external beam radiation therapy
|
Historical Control UCLA/Kaiser
n=110 Participants
A University of California, Los Angeles/Kaiser Permanente Los Angeles(KPLA) control cohort of newly diagnosed patients treated with first-line radiation therapy and temozolomide who had mostly received bevacizumab at recurrence was derived for comparison. Data excluded where records not complete
|
Total
n=180 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.4 years
n=99 Participants
|
59.4 years
n=107 Participants
|
59.305 years
n=206 Participants
|
|
Age, Customized
< 50 years
|
15 participants
n=99 Participants
|
30 participants
n=107 Participants
|
45 participants
n=206 Participants
|
|
Age, Customized
>= 50 years
|
55 participants
n=99 Participants
|
80 participants
n=107 Participants
|
135 participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=99 Participants
|
40 Participants
n=107 Participants
|
71 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=99 Participants
|
70 Participants
n=107 Participants
|
109 Participants
n=206 Participants
|
|
Enrollment by Site
UCLA
|
38 participants
n=99 Participants
|
61 participants
n=107 Participants
|
99 participants
n=206 Participants
|
|
Enrollment by Site
KPLA
|
32 participants
n=99 Participants
|
49 participants
n=107 Participants
|
81 participants
n=206 Participants
|
|
Karnofsky performance status
100
|
8 participants
n=99 Participants
|
13 participants
n=107 Participants
|
21 participants
n=206 Participants
|
|
Karnofsky performance status
90
|
27 participants
n=99 Participants
|
62 participants
n=107 Participants
|
89 participants
n=206 Participants
|
|
Karnofsky performance status
80
|
27 participants
n=99 Participants
|
23 participants
n=107 Participants
|
50 participants
n=206 Participants
|
|
Karnofsky performance status
70
|
5 participants
n=99 Participants
|
8 participants
n=107 Participants
|
13 participants
n=206 Participants
|
|
Karnofsky performance status
60
|
3 participants
n=99 Participants
|
4 participants
n=107 Participants
|
7 participants
n=206 Participants
|
|
Extent of surgery
Biopsy
|
2 participants
n=99 Participants
|
23 participants
n=107 Participants
|
25 participants
n=206 Participants
|
|
Extent of surgery
Subtotal resection
|
40 participants
n=99 Participants
|
40 participants
n=107 Participants
|
80 participants
n=206 Participants
|
|
Extent of surgery
Gross total resection
|
28 participants
n=99 Participants
|
47 participants
n=107 Participants
|
75 participants
n=206 Participants
|
|
Recursive partitioning analysis by class
III: MST 17.1
|
9 participants
n=99 Participants
|
27 participants
n=107 Participants
|
36 participants
n=206 Participants
|
|
Recursive partitioning analysis by class
IV: MST 11.2
|
32 participants
n=99 Participants
|
45 participants
n=107 Participants
|
77 participants
n=206 Participants
|
|
Recursive partitioning analysis by class
V: MST 7.5
|
29 participants
n=99 Participants
|
37 participants
n=107 Participants
|
66 participants
n=206 Participants
|
|
Recursive partitioning analysis by class
VI: MST 7.5
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
1 participants
n=206 Participants
|
|
Follow-up
|
24.2 years
n=99 Participants
|
41.8 years
n=107 Participants
|
36.616 years
n=206 Participants
|
|
Deaths
|
48 participants
n=99 Participants
|
89 participants
n=107 Participants
|
137 participants
n=206 Participants
|
|
Recurrent treatment
Progressed
|
56 participants
n=99 Participants
|
96 participants
n=107 Participants
|
152 participants
n=206 Participants
|
|
Recurrent treatment
Progressed with chemotherapy
|
39 participants
n=99 Participants
|
64 participants
n=107 Participants
|
103 participants
n=206 Participants
|
|
Recurrent treatment
Progressed with bevacizumab
|
29 participants
n=99 Participants
|
57 participants
n=107 Participants
|
86 participants
n=206 Participants
|
|
MGMT (O-6-Methylguanine-DNA Methyltransferase) promoter methylation
Methylated
|
29 participants
n=99 Participants
|
28 participants
n=107 Participants
|
57 participants
n=206 Participants
|
|
MGMT (O-6-Methylguanine-DNA Methyltransferase) promoter methylation
Unmethylated
|
41 participants
n=99 Participants
|
43 participants
n=107 Participants
|
84 participants
n=206 Participants
|
|
IDH1 (Isocitrate dehydrogenase 1 ) mutational status
Wild type
|
65 participants
n=99 Participants
|
68 participants
n=107 Participants
|
133 participants
n=206 Participants
|
|
IDH1 (Isocitrate dehydrogenase 1 ) mutational status
IDH1-R132H mutation
|
5 participants
n=99 Participants
|
3 participants
n=107 Participants
|
8 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 2 yearsOutcome measures
| Measure |
Treatment Arm
n=70 Participants
bevacizumab
temozolomide
external beam radiation therapy
|
Historical Control UCLA/KPLA
n=110 Participants
A University of California, Los Angeles/Kaiser Permanente Los Angeles(KPLA) control cohort of newly diagnosed patients treated with first-line radiation therapy and temozolomide who had mostly received bevacizumab at recurrence was derived for comparison.
|
|---|---|---|
|
Overall Survival
|
19.6 Months
Interval 16.1 to 23.3
|
21.1 Months
Interval 18.9 to 25.2
|
SECONDARY outcome
Timeframe: 2 yearsProgression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Outcome measures
| Measure |
Treatment Arm
n=70 Participants
bevacizumab
temozolomide
external beam radiation therapy
|
Historical Control UCLA/KPLA
n=110 Participants
A University of California, Los Angeles/Kaiser Permanente Los Angeles(KPLA) control cohort of newly diagnosed patients treated with first-line radiation therapy and temozolomide who had mostly received bevacizumab at recurrence was derived for comparison.
|
|---|---|---|
|
Time to Disease Progression
|
13.6 Months
Interval 11.1 to 16.5
|
7.6 Months
Interval 5.9 to 10.8
|
SECONDARY outcome
Timeframe: 6 monthsparticipants who were alive and disease progression free at 6 months
Outcome measures
| Measure |
Treatment Arm
n=70 Participants
bevacizumab
temozolomide
external beam radiation therapy
|
Historical Control UCLA/KPLA
n=110 Participants
A University of California, Los Angeles/Kaiser Permanente Los Angeles(KPLA) control cohort of newly diagnosed patients treated with first-line radiation therapy and temozolomide who had mostly received bevacizumab at recurrence was derived for comparison.
|
|---|---|---|
|
Progression-free Survival at 6 Months
|
88.4 percentage of participants
Interval 81.17 to 96.3
|
58.3 percentage of participants
Interval 49.7 to 68.4
|
SECONDARY outcome
Timeframe: 2 yearsRadiation therapy (RT) median from diagnosis to RT. Patients will have brain MRI evaluation of response and progression every 8 weeks starting from the day 56 scan obtained 2 weeks after completion of radiation and daily temozolomide and assessment will be conducted on a 7-point scale. This scale is expected to be more useful in this study because many newly-diagnosed patients are likely not to have evaluable disease due to gross total resections. Determination of whether progression occurs based on the day 56 scan will take into account the untreated window between baseline MRI and day of 1 of study. 7 Point Likert Scale: 3 to -3, 3 means complete resolution of tumor, and -3 means new lesion. A -2 or -3 assessment will be taken as tumor progression. complete resolution of tumor: 3 tumor resolved 3 tumor definitely smaller: 2 tumor probably smaller: 1 tumor unchanged: 0 tumor probably worse: -1 tumor definitely worse: -2 New Lesion: -3
Outcome measures
| Measure |
Treatment Arm
n=70 Participants
bevacizumab
temozolomide
external beam radiation therapy
|
Historical Control UCLA/KPLA
n=110 Participants
A University of California, Los Angeles/Kaiser Permanente Los Angeles(KPLA) control cohort of newly diagnosed patients treated with first-line radiation therapy and temozolomide who had mostly received bevacizumab at recurrence was derived for comparison.
|
|---|---|---|
|
Radiographic Response (When Evaluable)
|
4.14 Weeks
Interval 3.0 to 6.9
|
5 Weeks
Interval 1.7 to 10.7
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Description: Kaplan-Meier analysis of overall survival was performed.
IDH1 and MGMT methylation are important independent prognostic biomarkers that have to be included in a Cox regression model. In addition, subgroup analysis could reveal differential sensitivities to the treatment arm. The MGMT promoter methylation status, IDH1 mutation status were not available for all of the control samples. Therefore, only the samples with both info available were included in the analysis. Baseline analysis results are included in the Baseline Characteristics module.
Outcome measures
| Measure |
Treatment Arm
n=70 Participants
bevacizumab
temozolomide
external beam radiation therapy
|
Historical Control UCLA/KPLA
n=71 Participants
A University of California, Los Angeles/Kaiser Permanente Los Angeles(KPLA) control cohort of newly diagnosed patients treated with first-line radiation therapy and temozolomide who had mostly received bevacizumab at recurrence was derived for comparison.
|
|---|---|---|
|
Median Overall Survival (OS) Based on the MGMT Promoter Methylation Status
Median Overall survival of MGMT Methylated
|
24.7 months
Interval 11.7 to 38.2
|
26.7 months
Interval 3.5 to 43.2
|
|
Median Overall Survival (OS) Based on the MGMT Promoter Methylation Status
Median Overall survival of MGMT Unmethylated
|
15.9 months
Interval 5.7 to 31.5
|
18.2 months
Interval 2.1 to 48.1
|
Adverse Events
Bevacizumab, Temozolomide, External Beam Radiation
Serious events: 54 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bevacizumab, Temozolomide, External Beam Radiation
n=70 participants at risk
bevacizumab
temozolomide
external beam radiation therapy
|
|---|---|
|
General disorders
Acute dehydration
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Gastrointestinal disorders
Acute inferior wall MI
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Renal and urinary disorders
Acute renal failure
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Psychiatric disorders
Altered mental status
|
8.6%
6/70 • Number of events 7 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Gastrointestinal disorders
Bowel perforation
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
General disorders
Coma
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Cardiac disorders
congestive heart failure
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Investigations
Craniotomy wound w/cerebrospinal fluid leak
|
2.9%
2/70 • Number of events 2 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Vascular disorders
Deep vein thrombosis
|
2.9%
2/70 • Number of events 2 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Ear and labyrinth disorders
Falling episode/syncopal episode status post fall
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
General disorders
Fatigue
|
2.9%
2/70 • Number of events 2 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
General disorders
Flu like symptoms
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Infections and infestations
Fungal infection (Left lung)
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Gastrointestinal disorders
Gastroenteritis due to E. coli.
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Gastrointestinal disorders
GI Bleeding
|
2.9%
2/70 • Number of events 2 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
General disorders
Hypertension
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
General disorders
hypotention
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Eye disorders
Left retinal detachment
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Blood and lymphatic system disorders
leukopenia
|
1.4%
1/70 • Number of events 2 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Gastrointestinal disorders
Nausea
|
2.9%
2/70 • Number of events 2 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Blood and lymphatic system disorders
Nephritic proteinuria
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Blood and lymphatic system disorders
Nephrotic syndrome
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Blood and lymphatic system disorders
neutropenia
|
1.4%
1/70 • Number of events 2 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Renal and urinary disorders
obstructive uropathy
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Gastrointestinal disorders
Perforated sigmoid diverticulum
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Cardiac disorders
pulmonary embolism
|
5.7%
4/70 • Number of events 4 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Renal and urinary disorders
Renal failure
|
1.4%
1/70 • Number of events 2 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Nervous system disorders
Seizure
|
4.3%
3/70 • Number of events 3 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Psychiatric disorders
Steroid-induced psychosis
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Blood and lymphatic system disorders
Stroke
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Blood and lymphatic system disorders
thrombocytopenia
|
1.4%
1/70 • Number of events 2 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Blood and lymphatic system disorders
Transient Ischemic Attack
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Infections and infestations
Upper Resp. tract Infection
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Renal and urinary disorders
Urinary Tract Infection
|
1.4%
1/70 • Number of events 2 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Cardiac disorders
Ventriculoperitoneal shunt placement.
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Musculoskeletal and connective tissue disorders
Wound dehisicence of frontal wound
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Infections and infestations
Wound infection
|
1.4%
1/70 • Number of events 1 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Gastrointestinal disorders
vomiting
|
1.4%
1/70 • Number of events 2 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
Other adverse events
| Measure |
Bevacizumab, Temozolomide, External Beam Radiation
n=70 participants at risk
bevacizumab
temozolomide
external beam radiation therapy
|
|---|---|
|
General disorders
Fatigue
|
17.1%
12/70 • Number of events 12 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Blood and lymphatic system disorders
Hypertension
|
10.0%
7/70 • Number of events 7 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
Blood and lymphatic system disorders
Proteinuria
|
7.1%
5/70 • Number of events 5 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
|
General disorders
Syncope
|
7.1%
5/70 • Number of events 5 • Data collected through study completion, 2.25 years.
period coinciding with Aug 23, 2006 - Nov 26, 2008
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place