Trial Outcomes & Findings for Bevacizumab and Temozolomide Following Radiation and Chemotherapy for Newly Diagnosed Glioblastoma Multiforme (NCT NCT00590681)
NCT ID: NCT00590681
Last Updated: 2021-03-30
Results Overview
The best clinical response rates determined and 95% confidence intervals obtained using the exact binomial distribution.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
62 participants
Primary outcome timeframe
Up to 3 years
Results posted on
2021-03-30
Participant Flow
Participant milestones
| Measure |
Treatment
This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
Bevacizumab and Temozolomide: This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
|
|---|---|
|
Overall Study
STARTED
|
62
|
|
Overall Study
COMPLETED
|
42
|
|
Overall Study
NOT COMPLETED
|
20
|
Reasons for withdrawal
| Measure |
Treatment
This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
Bevacizumab and Temozolomide: This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
7
|
|
Overall Study
Adverse Event
|
8
|
|
Overall Study
Death
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
disease progression
|
1
|
Baseline Characteristics
There are 19 patients without gender information.
Baseline characteristics by cohort
| Measure |
Treatment
n=62 Participants
This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
Bevacizumab and Temozolomide: This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
|
|---|---|
|
Age, Continuous
|
60.4 years
n=62 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=43 Participants • There are 19 patients without gender information.
|
|
Sex: Female, Male
Male
|
24 Participants
n=43 Participants • There are 19 patients without gender information.
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=62 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=62 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=62 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=62 Participants
|
|
Race (NIH/OMB)
White
|
56 Participants
n=62 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=62 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=62 Participants
|
PRIMARY outcome
Timeframe: Up to 3 yearsPopulation: The forty-two participants did proceed to the post-RT phase.
The best clinical response rates determined and 95% confidence intervals obtained using the exact binomial distribution.
Outcome measures
| Measure |
Treatment
n=62 Participants
This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
Bevacizumab and Temozolomide: This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
|
|---|---|
|
Objective Response
Complete Response
|
22.5 percentage of participants
Interval 12.9 to 35.0
|
|
Objective Response
Partial Response
|
19.4 percentage of participants
Interval 10.4 to 31.4
|
|
Objective Response
Stable Disease
|
11.3 percentage of participants
Interval 4.7 to 21.9
|
|
Objective Response
Progression
|
6.5 percentage of participants
Interval 1.8 to 15.7
|
PRIMARY outcome
Timeframe: Up to 3 yearsPopulation: The forty-two participants did proceed to the post-RT phase, and 60 patients had valid data.
Outcome measures
| Measure |
Treatment
n=60 Participants
This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
Bevacizumab and Temozolomide: This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
|
|---|---|
|
Progression-free Survival (PFS)
|
0.96 years
Interval 0.8 to 1.68
|
SECONDARY outcome
Timeframe: Up to 3 yearsToxicity rates (limited toxicity to grade 4+)
Outcome measures
| Measure |
Treatment
n=62 Participants
This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
Bevacizumab and Temozolomide: This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
|
|---|---|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Apnea
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Bone infection
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Creatine phosphokinase increased
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
DIC
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Death
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Depression
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Fatigue
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Febrile neutropenia
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Hypocalcemia
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Ischemia cerebrovascular
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Leukocytes
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Leukopenia
|
2 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Metabolic
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Musculoskeletal
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Neutrophils
|
2 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Platelets
|
2 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Pleural effusion
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Proteinuria
|
2 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Seizure
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Soft tissue infection
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Thrombosis
|
1 Participants
|
|
Safety of Avastin in Combination With Temozolomide in This Study Population
Lymphopenia
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to 2 yearsDuration of response time from the first assessment of CR or PR until disease progression or death from any cause, whichever occurs first, event-free survival probability at two years assessed by Kaplan-Meier survivor function
Outcome measures
| Measure |
Treatment
n=24 Participants
This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
Bevacizumab and Temozolomide: This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
|
|---|---|
|
Duration of Response
|
38.8 probability
Interval 19.3 to 58.0
|
SECONDARY outcome
Timeframe: Up to 3 yearsPopulation: The forty-two participants did proceed to the post-RT phase, and 60 patients had valid data.
Outcome measures
| Measure |
Treatment
n=60 Participants
This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
Bevacizumab and Temozolomide: This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
|
|---|---|
|
Overall Survival
|
1.68 years
Interval 1.28 to 2.31
|
SECONDARY outcome
Timeframe: Up to 3 yearsPopulation: Zero participants were analyzed due to no data.
Outcome measures
Outcome data not reported
Adverse Events
Treatment
Serious events: 3 serious events
Other events: 53 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment
n=62 participants at risk
This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
Bevacizumab and Temozolomide: This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
|
|---|---|
|
Metabolism and nutrition disorders
Anorexia
|
1.6%
1/62
|
|
Nervous system disorders
Seizure
|
1.6%
1/62
|
|
Vascular disorders
Thrombosis
|
1.6%
1/62
|
Other adverse events
| Measure |
Treatment
n=62 participants at risk
This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
Bevacizumab and Temozolomide: This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
8.1%
5/62
|
|
Investigations
Alanine aminotransferase
|
24.2%
15/62
|
|
Investigations
Alkaline phosphatase
|
6.5%
4/62
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
54.8%
34/62
|
|
Metabolism and nutrition disorders
Anorexia
|
27.4%
17/62
|
|
Investigations
Aspartate aminotransferase increased
|
14.5%
9/62
|
|
Ear and labyrinth disorders
Auditory/Ear
|
9.7%
6/62
|
|
Investigations
Blood bicarbonate decreased
|
8.1%
5/62
|
|
Injury, poisoning and procedural complications
Bruising
|
9.7%
6/62
|
|
Psychiatric disorders
Confusion
|
14.5%
9/62
|
|
Gastrointestinal disorders
Constipation
|
43.5%
27/62
|
|
General disorders
Constitutional Symptoms
|
16.1%
10/62
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.9%
8/62
|
|
Endocrine disorders
Cushingoid
|
11.3%
7/62
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin
|
29.0%
18/62
|
|
Gastrointestinal disorders
Diarrhea
|
24.2%
15/62
|
|
Nervous system disorders
Dizziness
|
17.7%
11/62
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
9.7%
6/62
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
14.5%
9/62
|
|
Investigations
Ear, nose, and throat examination abnormal
|
11.3%
7/62
|
|
General disorders
Edema
|
22.6%
14/62
|
|
General disorders
Fatigue
|
74.2%
46/62
|
|
General disorders
Fever
|
8.1%
5/62
|
|
Nervous system disorders
Headache
|
38.7%
24/62
|
|
Gastrointestinal disorders
Heartburn
|
6.5%
4/62
|
|
Investigations
Hemoglobin
|
29.0%
18/62
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage nasal
|
14.5%
9/62
|
|
Hepatobiliary disorders
Hyperbilirubinemia
|
6.5%
4/62
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
40.3%
25/62
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
6.5%
4/62
|
|
Vascular disorders
Hypertension
|
21.0%
13/62
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
12.9%
8/62
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
24.2%
15/62
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
6.5%
4/62
|
|
Metabolism and nutrition disorders
Hypokalemia
|
6.5%
4/62
|
|
Metabolism and nutrition disorders
Hyponatremia
|
6.5%
4/62
|
|
Vascular disorders
Hypotension
|
6.5%
4/62
|
|
Infections and infestations
Infection
|
6.5%
4/62
|
|
Psychiatric disorders
Insomnia
|
14.5%
9/62
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
21.0%
13/62
|
|
Psychiatric disorders
Depression
|
11.3%
7/62
|
|
Blood and lymphatic system disorders
Leukocytes
|
19.4%
12/62
|
|
Blood and lymphatic system disorders
Lymphopenia
|
46.8%
29/62
|
|
Nervous system disorders
Memory impairment
|
16.1%
10/62
|
|
Metabolism and nutrition disorders
Metabolic/Lab
|
9.7%
6/62
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
27.4%
17/62
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal - Other
|
11.3%
7/62
|
|
Gastrointestinal disorders
Nausea
|
50.0%
31/62
|
|
Nervous system disorders
Neurological disorder NOS
|
9.7%
6/62
|
|
Psychiatric disorders
Neurology - Other
|
6.5%
4/62
|
|
Eye disorders
Ocular - Other
|
6.5%
4/62
|
|
General disorders
Pain
|
30.6%
19/62
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
22.6%
14/62
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
9.7%
6/62
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
6.5%
4/62
|
|
Investigations
Platelets
|
35.5%
22/62
|
|
Renal and urinary disorders
Proteinuria
|
9.7%
6/62
|
|
Infections and infestations
Pulmonary - Other
|
9.7%
6/62
|
|
Skin and subcutaneous tissue disorders
Rash
|
27.4%
17/62
|
|
Nervous system disorders
Seizure
|
12.9%
8/62
|
|
Nervous system disorders
Speech disorder
|
6.5%
4/62
|
|
Nervous system disorders
Taste alteration
|
14.5%
9/62
|
|
Vascular disorders
Thrombosis
|
8.1%
5/62
|
|
Nervous system disorders
Tremor
|
9.7%
6/62
|
|
Infections and infestations
Upper respiratory infection
|
8.1%
5/62
|
|
Renal and urinary disorders
Urinary frequency
|
12.9%
8/62
|
|
Infections and infestations
Urinary tract infection
|
8.1%
5/62
|
|
Eye disorders
Vision blurred
|
8.1%
5/62
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
8.1%
5/62
|
|
Gastrointestinal disorders
Vomiting
|
21.0%
13/62
|
|
Investigations
Neutrophils
|
8.1%
5/62
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place