Trial Outcomes & Findings for Study of Bevacizumab Plus Temodar and Tarceva in Patients With Glioblastoma or Gliosarcoma (NCT NCT00525525)
NCT ID: NCT00525525
Last Updated: 2014-11-14
Results Overview
Overall survival was defined from the date of diagnosis to date of death from any cause
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
74 participants
Primary outcome timeframe
Approximately 6-24 months
Results posted on
2014-11-14
Participant Flow
Participant milestones
| Measure |
Efficacy Group
Patients treated with the combination of radiation plus temozolomide (75 mg/m2 daily during radiotherapy) plus bevacizumab (10 mg/kg IV every two weeks during radiotherapy) plus tarceva (dose based upon use of EIAED, either 200 mg daily or 500 mg daily; given daily); all treatment begins at the start of radiotherapy and continues until tumor progression, death or excessive toxicity
|
Safety Lead-in Group
A safety lead-in group received bevacizumab and erlotinib added to TMZ after completion of radiation to rule out unexpected toxicity of the combination of drugs.
|
|---|---|---|
|
Overall Study
STARTED
|
59
|
15
|
|
Overall Study
COMPLETED
|
59
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of Bevacizumab Plus Temodar and Tarceva in Patients With Glioblastoma or Gliosarcoma
Baseline characteristics by cohort
| Measure |
Efficacy Group
n=59 Participants
Patients treated with the combination of radiation plus temozolomide (75 mg/m2 daily during radiotherapy) plus bevacizumab (10 mg/kg IV every two weeks during radiotherapy) plus tarceva (dose based upon use of EIAED, either 200 mg daily or 500 mg daily; given daily); all treatment begins at the start of radiotherapy and continues until tumor progression, death or excessive toxicity
|
Safety Lead-in Group
n=15 Participants
A safety lead-in group received bevacizumab and erlotinib added to TMZ after completion of radiation to rule out unexpected toxicity of the combination of drugs.
|
Total
n=74 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54 years
n=5 Participants
|
65 years
n=7 Participants
|
58 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
59 participants
n=5 Participants
|
15 participants
n=7 Participants
|
74 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Approximately 6-24 monthsOverall survival was defined from the date of diagnosis to date of death from any cause
Outcome measures
| Measure |
Efficacy Group
n=59 Participants
Patients treated with the combination of radiation plus temozolomide (75 mg/m2 daily during radiotherapy) plus bevacizumab (10 mg/kg IV every two weeks during radiotherapy) plus tarceva (dose based upon use of EIAED, either 200 mg daily or 500 mg daily; given daily); all treatment begins at the start of radiotherapy and continues until tumor progression, death or excessive toxicity
|
|---|---|
|
Overall Survival (OS)
|
19.8 months
Interval 17.1 to 28.6
|
PRIMARY outcome
Timeframe: Within 8 weeks of initiating study therapyUnexpected severe study-related adverse events
Outcome measures
| Measure |
Efficacy Group
n=15 Participants
Patients treated with the combination of radiation plus temozolomide (75 mg/m2 daily during radiotherapy) plus bevacizumab (10 mg/kg IV every two weeks during radiotherapy) plus tarceva (dose based upon use of EIAED, either 200 mg daily or 500 mg daily; given daily); all treatment begins at the start of radiotherapy and continues until tumor progression, death or excessive toxicity
|
|---|---|
|
Unexpected Toxicities During First 2 Cycles of Study Drug
|
0 Events
|
SECONDARY outcome
Timeframe: Approximately 6 months to 1 yearProgression-free survival was defined from the date of diagnosis to the date that progressive disease was first observed on imaging, or the date at which nonreversible neurologic progression or permanently increased corticosteroid requirement, death from any cause, or early discontinuation of treatment. Imaging guidelines were used to evaluate progression: (i) 25% increase in the sum of products of all measurable lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline; (ii) clear worsening of any assessable disease; (iii) appearance of any new lesion/site; and (iv) clear clinical worsening or failure to return for evaluation as a result of death or deteriorating condition (unless clearly unrelated to this cancer).
Outcome measures
| Measure |
Efficacy Group
n=59 Participants
Patients treated with the combination of radiation plus temozolomide (75 mg/m2 daily during radiotherapy) plus bevacizumab (10 mg/kg IV every two weeks during radiotherapy) plus tarceva (dose based upon use of EIAED, either 200 mg daily or 500 mg daily; given daily); all treatment begins at the start of radiotherapy and continues until tumor progression, death or excessive toxicity
|
|---|---|
|
Progression-free Survival
|
13.5 months
Interval 12.2 to 17.0
|
Adverse Events
Efficacy Group
Serious events: 32 serious events
Other events: 53 other events
Deaths: 0 deaths
Safety Lead-in Group
Serious events: 7 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Efficacy Group
n=59 participants at risk
Patients treated with the combination of radiation plus temozolomide (75 mg/m2 daily during radiotherapy) plus bevacizumab (10 mg/kg IV every two weeks during radiotherapy) plus tarceva (dose based upon use of EIAED, either 200 mg daily or 500 mg daily; given daily); all treatment begins at the start of radiotherapy and continues until tumor progression, death or excessive toxicity
|
Safety Lead-in Group
n=15 participants at risk
A safety lead-in group received bevacizumab and erlotinib added to TMZ after completion of radiation to rule out unexpected toxicity of the combination of drugs.
|
|---|---|---|
|
Immune system disorders
Infection
|
11.9%
7/59 • Duration of study treatment (up to 24 months after initial radiation)
|
26.7%
4/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Vascular disorders
Thrombosis/thrombus/embolism
|
6.8%
4/59 • Duration of study treatment (up to 24 months after initial radiation)
|
13.3%
2/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Nervous system disorders
Personality/behavioral
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Nervous system disorders
Seizure
|
13.6%
8/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Vascular disorders
Cerebrovascular ischemia
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
3.4%
2/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Nervous system disorders
Ataxia
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Nervous system disorders
Cognitive disturbance
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Gastrointestinal disorders
Dysphagia
|
3.4%
2/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Nervous system disorders
Neuropathy
|
0.00%
0/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Immune system disorders
Allergic reaction/hypersensitivity
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Nervous system disorders
Confusion
|
3.4%
2/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
General disorders
Death
|
3.4%
2/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
General disorders
Dehydration
|
6.8%
4/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Gastrointestinal disorders
Diarrhea
|
5.1%
3/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Injury, poisoning and procedural complications
Fracture
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Vascular disorders
Hemorrhage (CNS)
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Gastrointestinal disorders
Mucositis
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
General disorders
Nausea
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
General disorders
Headache
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Blood and lymphatic system disorders
Hyponatremia
|
3.4%
2/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Nervous system disorders
Speech impairment
|
3.4%
2/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Cardiac disorders
Cardiac ischemia/infarction
|
0.00%
0/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
General disorders
Vomiting
|
0.00%
0/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Skin and subcutaneous tissue disorders
Wound complication (non-infectious)
|
0.00%
0/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
General disorders
Weight Loss
|
0.00%
0/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
Other adverse events
| Measure |
Efficacy Group
n=59 participants at risk
Patients treated with the combination of radiation plus temozolomide (75 mg/m2 daily during radiotherapy) plus bevacizumab (10 mg/kg IV every two weeks during radiotherapy) plus tarceva (dose based upon use of EIAED, either 200 mg daily or 500 mg daily; given daily); all treatment begins at the start of radiotherapy and continues until tumor progression, death or excessive toxicity
|
Safety Lead-in Group
n=15 participants at risk
A safety lead-in group received bevacizumab and erlotinib added to TMZ after completion of radiation to rule out unexpected toxicity of the combination of drugs.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
8.5%
5/59 • Duration of study treatment (up to 24 months after initial radiation)
|
13.3%
2/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
11.9%
7/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Blood and lymphatic system disorders
Leukocytes
|
18.6%
11/59 • Duration of study treatment (up to 24 months after initial radiation)
|
13.3%
2/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Blood and lymphatic system disorders
Lymphopenia
|
66.1%
39/59 • Duration of study treatment (up to 24 months after initial radiation)
|
53.3%
8/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
10.2%
6/59 • Duration of study treatment (up to 24 months after initial radiation)
|
13.3%
2/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Blood and lymphatic system disorders
Platelets
|
23.7%
14/59 • Duration of study treatment (up to 24 months after initial radiation)
|
13.3%
2/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.8%
4/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Nervous system disorders
Seizure
|
16.9%
10/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Gastrointestinal disorders
Vomiting
|
5.1%
3/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
General disorders
Weight loss
|
13.6%
8/59 • Duration of study treatment (up to 24 months after initial radiation)
|
0.00%
0/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
General disorders
Anorexia
|
0.00%
0/59 • Duration of study treatment (up to 24 months after initial radiation)
|
13.3%
2/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Cardiac disorders
Cardiac troponin
|
0.00%
0/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Nervous system disorders
Confusion
|
0.00%
0/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Blood and lymphatic system disorders
Hyperglycemia
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Vascular disorders
Hydrocephalus
|
0.00%
0/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Vascular disorders
Hypertension
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Blood and lymphatic system disorders
INR (International Normalized Ratio of prothrombin time)
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
13.3%
2/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Nervous system disorders
Mood alteration - agitation
|
0.00%
0/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
General disorders
Nausea
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Nervous system disorders
Neuropathy
|
0.00%
0/59 • Duration of study treatment (up to 24 months after initial radiation)
|
26.7%
4/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Blood and lymphatic system disorders
PTT (partial Thromboplastin Time)
|
0.00%
0/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
Nervous system disorders
Speech impairment (dysphagia/aphagia)
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
|
General disorders
Syncope
|
1.7%
1/59 • Duration of study treatment (up to 24 months after initial radiation)
|
6.7%
1/15 • Duration of study treatment (up to 24 months after initial radiation)
|
Additional Information
Michael D. Prados, MD, FACP
University of California San Francisco
Phone: 415-353-2383
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place