Trial Outcomes & Findings for Effect of Bevacizumab on Radiation-induced Brain Necrosis in Patients With Nasopharyngeal Carcinoma (NCT NCT01621880)
NCT ID: NCT01621880
Last Updated: 2019-01-09
Results Overview
The primary outcome of the trial was the treatment response rate at two months. The definitions of response and progressive disease were based on both the radiographic changes and clinical symptoms. We defined response as both (1)a reduction in edema volume on FLAIR images by ≥25% and (2)no deteriorating symptoms. Progressive disease was defined as either (1)larger than 10% increase in the volume of the lesions; (2)appearance of any new lesion/site; or (3)clear clinical worsening.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
112 participants
Primary outcome timeframe
At 2 months.
Results posted on
2019-01-09
Participant Flow
Participant milestones
| Measure |
Bevacizumab
Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
bevacizumab: Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
|
Corticosteroid
Patients in the corticosteroid group were treated with methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
Corticosteroid: Patients in the corticosteroid group were treated with intravenous pulsed-steroid therapy: methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
|
|---|---|---|
|
Overall Study
STARTED
|
58
|
54
|
|
Overall Study
COMPLETED
|
48
|
49
|
|
Overall Study
NOT COMPLETED
|
10
|
5
|
Reasons for withdrawal
| Measure |
Bevacizumab
Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
bevacizumab: Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
|
Corticosteroid
Patients in the corticosteroid group were treated with methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
Corticosteroid: Patients in the corticosteroid group were treated with intravenous pulsed-steroid therapy: methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
|
|---|---|---|
|
Overall Study
Adverse Event
|
5
|
1
|
|
Overall Study
Withdrawal by Subject
|
5
|
4
|
Baseline Characteristics
Effect of Bevacizumab on Radiation-induced Brain Necrosis in Patients With Nasopharyngeal Carcinoma
Baseline characteristics by cohort
| Measure |
Bevacizumab
n=58 Participants
Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
bevacizumab: Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
|
Corticosteroid
n=54 Participants
Patients in the corticosteroid group were treated with methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
Corticosteroid: Patients in the corticosteroid group were treated with methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
|
Total
n=112 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
49.3 years
STANDARD_DEVIATION 7.0 • n=99 Participants
|
50.5 years
STANDARD_DEVIATION 8.6 • n=107 Participants
|
50.1 years
STANDARD_DEVIATION 8.5 • n=206 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=99 Participants
|
39 Participants
n=107 Participants
|
77 Participants
n=206 Participants
|
|
Region of Enrollment
China
|
58 participants
n=99 Participants
|
54 participants
n=107 Participants
|
112 participants
n=206 Participants
|
|
Conventional radiotherapy
|
41 Participants
n=99 Participants
|
36 Participants
n=107 Participants
|
77 Participants
n=206 Participants
|
|
IMRT(intensity modulated radiation therapy)
|
17 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
|
Dose of nasopharyngeal radiation
|
69.4 Gy
STANDARD_DEVIATION 5.2 • n=99 Participants
|
71.1 Gy
STANDARD_DEVIATION 2.4 • n=107 Participants
|
70.3 Gy
STANDARD_DEVIATION 4.1 • n=206 Participants
|
|
Dose of neck radiation
|
58.9 Gy
STANDARD_DEVIATION 8.1 • n=99 Participants
|
40.7 Gy
STANDARD_DEVIATION 10.3 • n=107 Participants
|
49.7 Gy
STANDARD_DEVIATION 13.0 • n=206 Participants
|
PRIMARY outcome
Timeframe: At 2 months.The primary outcome of the trial was the treatment response rate at two months. The definitions of response and progressive disease were based on both the radiographic changes and clinical symptoms. We defined response as both (1)a reduction in edema volume on FLAIR images by ≥25% and (2)no deteriorating symptoms. Progressive disease was defined as either (1)larger than 10% increase in the volume of the lesions; (2)appearance of any new lesion/site; or (3)clear clinical worsening.
Outcome measures
| Measure |
Bevacizumab
n=58 Participants
Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
bevacizumab: Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
|
Corticosteroid
n=54 Participants
Patients in the corticosteroid group were treated with methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
Corticosteroid: Patients in the corticosteroid group were treated with intravenous pulsed-steroid therapy: methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
|
|---|---|---|
|
Number of Participants With a Treatment Response
|
38 Participants
|
17 Participants
|
SECONDARY outcome
Timeframe: Change from baseline to evaluation at 2 months.T1 post-gadolinium imaging was used to measure the enhancement and T2-weighted FLAIR to measure the edema. For lesion measurements, radiologists used manual and semiautomatic approaches to identify the outline of the lesion, and the total volume was estimated with Volume Viewer 2 software(GE Healthcare, AW Suite2.0 6.5.1.z).
Outcome measures
| Measure |
Bevacizumab
n=48 Participants
Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
bevacizumab: Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
|
Corticosteroid
n=49 Participants
Patients in the corticosteroid group were treated with methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
Corticosteroid: Patients in the corticosteroid group were treated with intravenous pulsed-steroid therapy: methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
|
|---|---|---|
|
Percentage Change in Radiological Measures of Lesion Volume
Percentage Change in FLAIR
|
-51.8 percentage
Standard Deviation 39.9
|
-19.3 percentage
Standard Deviation 42.5
|
|
Percentage Change in Radiological Measures of Lesion Volume
Percentage Change in enhancement
|
-25.5 percentage
Standard Deviation 45.2
|
-5.0 percentage
Standard Deviation 44.2
|
Adverse Events
Bevacizumab
Serious events: 1 serious events
Other events: 25 other events
Deaths: 0 deaths
Corticosteroid
Serious events: 1 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bevacizumab
n=58 participants at risk
Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
bevacizumab: Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
|
Corticosteroid
n=54 participants at risk
Patients in the corticosteroid group were treated with methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
Corticosteroid: Patients in the corticosteroid group were treated with intravenous pulsed-steroid therapy: methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
|
|---|---|---|
|
Nervous system disorders
Ischemic stroke
|
1.7%
1/58 • Number of events 1 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
0.00%
0/54 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
|
Infections and infestations
Infection
|
0.00%
0/58 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
1.9%
1/54 • Number of events 1 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
Other adverse events
| Measure |
Bevacizumab
n=58 participants at risk
Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
bevacizumab: Patients receive bevacizumab 5mg/kg intravenously over 30-90 minutes on day1. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
|
Corticosteroid
n=54 participants at risk
Patients in the corticosteroid group were treated with methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
Corticosteroid: Patients in the corticosteroid group were treated with intravenous pulsed-steroid therapy: methylprednisolone 500 mg daily intravenously for three consecutive days followed by oral prednisone 60 mg for five days and gradually tapered 15mg every 5 days. When the prednisone dose reached 30mg per day, it was tapered down more slowly (tapered 5mg every week), until a maintenance dose of 10mg per day was reached. The entire intervention lasted two months. At 2 months, prednisone was stopped.
|
|---|---|---|
|
Cardiac disorders
Hypertension
|
20.7%
12/58 • Number of events 12 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
18.5%
10/54 • Number of events 10 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
|
General disorders
Fatigued
|
12.1%
7/58 • Number of events 7 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
3.7%
2/54 • Number of events 2 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
|
Nervous system disorders
Hemorrhage
|
6.9%
4/58 • Number of events 4 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
3.7%
2/54 • Number of events 2 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
|
General disorders
Insomnia
|
5.2%
3/58 • Number of events 3 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
14.8%
8/54 • Number of events 8 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
|
Nervous system disorders
Headache
|
5.2%
3/58 • Number of events 3 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
7.4%
4/54 • Number of events 4 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.2%
3/58 • Number of events 3 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
0.00%
0/54 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
|
Blood and lymphatic system disorders
Fever
|
3.4%
2/58 • Number of events 2 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
5.6%
3/54 • Number of events 3 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
|
Eye disorders
Blurred vision
|
1.7%
1/58 • Number of events 1 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
7.4%
4/54 • Number of events 4 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
|
Endocrine disorders
Hyperglycemia
|
1.7%
1/58 • Number of events 1 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
14.8%
8/54 • Number of events 8 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
|
General disorders
Gain weight
|
0.00%
0/58 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
9.3%
5/54 • Number of events 5 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
|
Infections and infestations
Infection
|
6.9%
4/58 • Number of events 4 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
9.3%
5/54 • Number of events 5 • Adverse event data were collected from the beginning of randomization to 6 months after treatment.
|
Additional Information
Yamei Tang
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Phone: 08613556001992
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60