Trial Outcomes & Findings for A Study of Avastin (Bevacizumab) and Irinotecan Versus Temozolomide Radiochemistry in Patients With Glioblastoma (NCT NCT00967330)
NCT ID: NCT00967330
Last Updated: 2015-11-20
Results Overview
Progression-free survival was defined as the time from randomization to objective tumor progression or death from any cause, whichever came first. Progression was defined as 25 percent (%) increase in size of enhancing tumor or any new tumor on gadolinium contrast agent magnetic resonance imaging (Gd-MRI) scans, or neurologically worse, and steroids stable or increased. Percentage of participants achieving PFS without disease progression or death was reported.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
182 participants
Primary outcome timeframe
6 months
Results posted on
2015-11-20
Participant Flow
Participant milestones
| Measure |
Bevacizumab + Irinotecan
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Overall Study
STARTED
|
122
|
60
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
122
|
60
|
Reasons for withdrawal
| Measure |
Bevacizumab + Irinotecan
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Overall Study
Protocol Violation
|
3
|
4
|
|
Overall Study
Regular
|
10
|
3
|
|
Overall Study
Withdrawal by Subject
|
6
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Death
|
102
|
51
|
|
Overall Study
Severe protocol deviation
|
0
|
1
|
Baseline Characteristics
A Study of Avastin (Bevacizumab) and Irinotecan Versus Temozolomide Radiochemistry in Patients With Glioblastoma
Baseline characteristics by cohort
| Measure |
Bevacizumab + Irinotecan
n=122 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=60 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
Total
n=182 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.4 years
STANDARD_DEVIATION 10.17 • n=5 Participants
|
56.4 years
STANDARD_DEVIATION 10.84 • n=7 Participants
|
55.7 years
STANDARD_DEVIATION 10.37 • n=5 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
83 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
122 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: Intent-to-treat (ITT) population included participants randomized for whom it cannot be ruled out, that they took study medication at least once and where primary variable was measured at least once under study medication. Data were analyzed according to the treatment randomized (as randomized).
Progression-free survival was defined as the time from randomization to objective tumor progression or death from any cause, whichever came first. Progression was defined as 25 percent (%) increase in size of enhancing tumor or any new tumor on gadolinium contrast agent magnetic resonance imaging (Gd-MRI) scans, or neurologically worse, and steroids stable or increased. Percentage of participants achieving PFS without disease progression or death was reported.
Outcome measures
| Measure |
Bevacizumab + Irinotecan
n=116 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=54 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months
|
79.31 percentage of participants
Interval 68.859 to 84.617
|
42.59 percentage of participants
Interval 26.68 to 53.05
|
SECONDARY outcome
Timeframe: From baseline to the end of the study (up to 4.5 years)Population: ITT population. Data were analyzed according to the treatment randomized (as randomized).
Progression-free survival was defined as the time from randomization to objective tumor progression or death from any cause, whichever came first. Progression was defined as 25% increase in size of enhancing tumor or any new tumor on Gd-MRI scans, or neurologically worse, and steroids stable or increased. PFS was estimated using Kaplan-Meier method.
Outcome measures
| Measure |
Bevacizumab + Irinotecan
n=116 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=54 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Progression-Free Survival (PFS)
|
9.74 Months
Interval 8.72 to 10.76
|
5.99 Months
Interval 2.73 to 6.15
|
SECONDARY outcome
Timeframe: From baseline until death (up to 4.5 years)Population: ITT population. Data were analyzed according to the treatment randomized (as randomized).
Overall survival was defined as the time from randomization to death from any cause. OS was estimated using Kaplan-Meier method.
Outcome measures
| Measure |
Bevacizumab + Irinotecan
n=116 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=54 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Overall Survival (OS)
|
16.64 Months
Interval 15.43 to 18.36
|
17.30 Months
Interval 14.77 to 20.36
|
SECONDARY outcome
Timeframe: From baseline until death (up to 4.5 years)Population: ITT population
Discontinuation was defined as the percentage of participants who permanently discontinued treatment in either treatment arm. Percentage of participant with individual discontinuation reason are reported. CNS: central nervous system; CTCAE: Common Terminology Criteria for Adverse Events . Other reason refers to any other reason than the specified ones.
Outcome measures
| Measure |
Bevacizumab + Irinotecan
n=116 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=54 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Percentage of Participants Who Discontinued
Wound dehiscence requiring medical intervention
|
0.9 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Who Discontinued
Persisting non-hematological toxicity CTCAE Grade3
|
0 percentage of participants
|
1.9 percentage of participants
|
|
Percentage of Participants Who Discontinued
CNS hemorrhagic event (CTCAE Grade >1)
|
0.9 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Who Discontinued
Gastro-intestinal perforation (CTCAE Grade 1-4)
|
0.9 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Who Discontinued
Other
|
9.5 percentage of participants
|
5.6 percentage of participants
|
|
Percentage of Participants Who Discontinued
Participant's wish
|
6 percentage of participants
|
5.6 percentage of participants
|
|
Percentage of Participants Who Discontinued
Progressive disease
|
74.1 percentage of participants
|
57.4 percentage of participants
|
|
Percentage of Participants Who Discontinued
Proteinuria (nephrotic syndrome) (CTCAE Grade 4)
|
0.9 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Who Discontinued
Regular
|
1.7 percentage of participants
|
27.8 percentage of participants
|
|
Percentage of Participants Who Discontinued
Repeated CTCAE Grade 4 hematological toxicity
|
0 percentage of participants
|
0.9 percentage of participants
|
|
Percentage of Participants Who Discontinued
Venous thrombosis/embolism
|
0.9 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Who Discontinued
Wound dehiscence requiring surgical intervention
|
4.3 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: 4 week after radiotherapy (RT) (up to Week 4), >4 Week after RT (up to Week 8) and Month 6Population: ITT population. Data were analyzed according to the treatment randomized (as randomized). Here, number of participants analyzed = participants who were evaluable for this outcome and n = participants who were evaluable of specified time-point.
BOR was defined as the best response observed for a participant during assessment. Number of participants who had BOR as CR and number of participants who had BOR as CR or PR were reported. Complete response was defined as disappearance of all enhancing tumor on consecutive Gd-MRI scans at least 1 month apart, off steroids, and neurologically stable or improved. Partial response was defined as 50% reduction in size of enhancing tumor on consecutive Gd-MRI scans at least 1 month apart, steroids stable or reduced, and neurologically stable or improved.
Outcome measures
| Measure |
Bevacizumab + Irinotecan
n=110 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=46 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR)
CR at 4 weeks after RT (n=110,46)
|
11 participants
|
2 participants
|
|
Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR)
CR at >4 weeks after RT (n=95,35)
|
11 participants
|
1 participants
|
|
Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR)
CR at Month 6 (n=91,28)
|
3 participants
|
1 participants
|
|
Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR)
CR or PR at 4 Week after RT (n=110,46)
|
42 participants
|
6 participants
|
|
Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR)
CR or PR at >4 Week after RT (n=95,35)
|
18 participants
|
3 participants
|
|
Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR)
CR or PR at Month 6 (n=91,28)
|
5 participants
|
3 participants
|
SECONDARY outcome
Timeframe: At screening, Baseline, Month 6 and Therapy Discontinuation (Up to 4.5 years)Population: ITT population. Here, n = participants with at least 1 assessment during specified time-point.
FLAIR lesions were determined as "stable", "progressive" or "decreased". FLAIR lesions was determined as "progressive" only if they were not be attributed to causes apart from tumor infiltration (sequelae of radiation therapy, demyelination, ischemia, infection, seizures, or other treatment effects). Percentage of participants are based on ITT population. Dis.=Discontinuation.
Outcome measures
| Measure |
Bevacizumab + Irinotecan
n=116 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=54 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Percentage of Participants With Response on FLAIR Imaging
Therapy Dis.:Decreased FLAIR Lesions (n=55,31)
|
0.9 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Response on FLAIR Imaging
Screening: Initial Flair Lesion (n=116,54)
|
72.4 percentage of participants
|
72.2 percentage of participants
|
|
Percentage of Participants With Response on FLAIR Imaging
Screening:Stable Flair Lesion (n=116,54)
|
17.2 percentage of participants
|
16.7 percentage of participants
|
|
Percentage of Participants With Response on FLAIR Imaging
Baseline:Decreased FLAIR Lesions (n=105,46)
|
16.4 percentage of participants
|
20.4 percentage of participants
|
|
Percentage of Participants With Response on FLAIR Imaging
Baseline:Initial FLAIR Lesions (n=105,46)
|
18.1 percentage of participants
|
18.5 percentage of participants
|
|
Percentage of Participants With Response on FLAIR Imaging
Baseline:Progressive FLAIR Lesions (n=105,46)
|
14.7 percentage of participants
|
11.1 percentage of participants
|
|
Percentage of Participants With Response on FLAIR Imaging
Baseline: Stable FLAIR Lesions (n=105,46)
|
41.4 percentage of participants
|
35.2 percentage of participants
|
|
Percentage of Participants With Response on FLAIR Imaging
Month 6:Progressive FLAIR Lesions (n=91,28)
|
16.4 percentage of participants
|
22.2 percentage of participants
|
|
Percentage of Participants With Response on FLAIR Imaging
Month 6: Stable FLAIR Lesions (n=91,28)
|
62.1 percentage of participants
|
29.6 percentage of participants
|
|
Percentage of Participants With Response on FLAIR Imaging
Therapy Dis.:Progressiv FLAIR Lesions (n=55,31)
|
29.3 percentage of participants
|
27.8 percentage of participants
|
|
Percentage of Participants With Response on FLAIR Imaging
Therapy Dis.:Stable FLAIR Lesions (n=55,31)
|
17.2 percentage of participants
|
29.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Post-Baseline (up to Month 30)Population: ITT population.
The EORTC QLQ-C30 incorporates: 5 functional scales (physical, role, cognitive, emotional, and social); 9 symptom scales (fatigue, pain, nausea and vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties); and a global health and quality-of-life scale. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to 0-100 scale; higher score for Global Qol/functional scales=better level of functioning or a higher score for symptom scale=greater degree of symptoms. The change in global health status was determined to be the difference in values at baseline and each specific visit. The term ''baseline'' refers to the time of randomization to the maintenance phase.
Outcome measures
| Measure |
Bevacizumab + Irinotecan
n=116 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=54 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Physical Functioning
|
-8.3513 units on a scale
Interval -11.8714 to -4.8312
|
-6.2511 units on a scale
Interval -11.213 to -1.2892
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Role Functioning
|
-0.7635 units on a scale
Interval -6.1695 to 4.6425
|
-2.2339 units on a scale
Interval -9.9836 to 5.5159
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Emotional Functioning
|
2.2774 units on a scale
Interval -1.7409 to 6.2958
|
2.2547 units on a scale
Interval -3.4834 to 7.9928
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Cognitive Functioning
|
-2.0188 units on a scale
Interval -6.2256 to 2.188
|
-3.8401 units on a scale
Interval -9.8118 to 2.1317
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Social Functioning
|
-6.2324 units on a scale
Interval -11.348 to -1.1169
|
-4.6198 units on a scale
Interval -11.9009 to 2.6613
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Global health Status /QoL (ql)
|
-3.1134 units on a scale
Interval -6.5412 to 0.3145
|
0.3855 units on a scale
Interval -4.422 to 5.193
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Fatique
|
5.5228 units on a scale
Interval 1.6424 to 9.4031
|
2.1779 units on a scale
Interval -3.3223 to 7.6781
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Nausea/Vomitting
|
8.9557 units on a scale
Interval 6.5139 to 11.3974
|
4.7597 units on a scale
Interval 1.3958 to 8.1235
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Pain
|
10.6876 units on a scale
Interval 5.8004 to 15.5747
|
1.5926 units on a scale
Interval -5.3301 to 8.5152
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Dyspnoea
|
3.7134 units on a scale
Interval -0.3957 to 7.8226
|
0.5046 units on a scale
Interval -5.2542 to 6.2635
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Insomnia
|
-2.6266 units on a scale
Interval -7.8402 to 2.587
|
-7.5026 units on a scale
Interval -14.8641 to -0.1411
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Appetite loss
|
13.7423 units on a scale
Interval 9.9118 to 17.5727
|
10.9601 units on a scale
Interval 5.6151 to 16.3051
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Constipation
|
8.0230 units on a scale
Interval 3.9214 to 12.1246
|
4.0855 units on a scale
Interval -1.6913 to 9.8624
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Diarrhoea
|
6.0230 units on a scale
Interval 2.9313 to 9.1147
|
-0.1455 units on a scale
Interval -4.3834 to 4.0925
|
|
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
Financial Problems
|
4.8435 units on a scale
Interval 0.03603 to 9.651
|
2.1140 units on a scale
Interval -4.7005 to 8.9284
|
SECONDARY outcome
Timeframe: Baseline, Post-Baseline (up to Month 30)Population: ITT population
EORTC QLQ-BN20 consisted of 20 items assessing visual disorders, motor dysfunction, communication deficit, various disease symptoms (e.g. headaches and seizures), treatment toxicities (e.g. hair loss) and future uncertainty. All of the 20 items are rated on a 4 point Likert scale from 1=not at all, 2=a little, 3=quite a bit and 4=very much, and were linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.
Outcome measures
| Measure |
Bevacizumab + Irinotecan
n=116 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=54 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
Future uncertainty
|
-5.2779 units on a scale
Interval -9.2589 to -1.2968
|
-8.5478 units on a scale
Interval -14.3337 to -2.7619
|
|
Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
Visual disorder
|
-2.0869 units on a scale
Interval -4.5092 to 0.3354
|
-3.202 units on a scale
Interval -6.7584 to 0.3528
|
|
Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
Motor dysfunction
|
5.4416 units on a scale
Interval 2.3943 to 8.4888
|
6.5429 units on a scale
Interval 2.1426 to 10.9433
|
|
Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
Communication deficit
|
4.7440 units on a scale
Interval 1.6899 to 7.798
|
4.6431 units on a scale
Interval 0.2253 to 9.0609
|
|
Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
Headaches
|
4.3905 units on a scale
Interval 0.6465 to 8.1345
|
-3.9389 units on a scale
Interval -9.2879 to 1.4101
|
|
Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
Drowsines
|
11.7204 units on a scale
Interval 7.6425 to 15.7983
|
8.2805 units on a scale
Interval 2.3973 to 14.1637
|
|
Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
Hair loss
|
11.9235 units on a scale
Interval 7.6344 to 16.2127
|
7.3328 units on a scale
Interval 1.0111 to 13.6545
|
|
Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
Itchy skin
|
5.4882 units on a scale
Interval 2.0875 to 8.889
|
6.4690 units on a scale
Interval 1.5048 to 11.4331
|
|
Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
Weakness of legs
|
8.9586 units on a scale
Interval 4.9123 to 13.0048
|
7.9245 units on a scale
Interval 2.0687 to 13.7804
|
|
Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
Bladder control
|
1.5020 units on a scale
Interval -1.0917 to 4.0957
|
1.9710 units on a scale
Interval -1.8122 to 5.7543
|
SECONDARY outcome
Timeframe: Baseline, Post-Baseline (up to Month 30)Population: ITT population.
The MMSE briefly measures orientation to time and place, immediate recall, short-term verbal memory, calculation, language and construct ability. Each area tested had a designated point value, the total score can range from 0 to 30, with a higher score indicating better function.
Outcome measures
| Measure |
Bevacizumab + Irinotecan
n=116 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=54 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30)
Repetitions required
|
-0.05763 units on a scale
Interval -0.1971 to 0.0818
|
0.08530 units on a scale
Interval -0.1212 to 0.2918
|
|
Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30)
Orientation to time and place
|
-0.01771 units on a scale
Interval -0.1406 to 0.1052
|
-0.2110 units on a scale
Interval -0.3907 to -0.03135
|
|
Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30)
Immediate recall
|
-0.00264 units on a scale
Interval -0.02163 to 0.01635
|
-0.03219 units on a scale
Interval -0.05888 to -0.00551
|
|
Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30)
Calculations
|
-0.2153 units on a scale
Interval -0.3911 to -0.03952
|
-0.2120 units on a scale
Interval -0.4706 to 0.04652
|
|
Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30)
Short-term verbal memory
|
0.2012 units on a scale
Interval 0.106 to 0.2964
|
0.1634 units on a scale
Interval 0.02332 to 0.3034
|
|
Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30)
Language and construct ability
|
-0.1254 units on a scale
Interval -0.2416 to -0.00908
|
-0.2057 units on a scale
Interval -0.3765 to -0.03499
|
|
Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30)
Total Score
|
-0.2871 units on a scale
Interval -0.7647 to 0.1905
|
-0.5999 units on a scale
Interval -1.3069 to 0.1071
|
SECONDARY outcome
Timeframe: Baseline, Post-Baseline (up to Month 30)Population: ITT population
KPS is an 11-level score (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100) which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks. Deterioration in KPS was defined as decrease of 20 or more points in KPS score.
Outcome measures
| Measure |
Bevacizumab + Irinotecan
n=116 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=54 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Change From Baseline for Karnofsky Performance Status (KPS) Score at Baseline, Post-Baseline (up to Month 30)
|
-3.3399 units on a scale
Interval -5.2132 to -1.4666
|
-5.4909 units on a scale
Interval -8.2693 to -2.7126
|
SECONDARY outcome
Timeframe: From baseline to Month 6Population: The safety population (SAF) was defined to include all participants who received at least 1 dose of study medication. Data were analyzed according to the treatment actually received (as treated).
Participants used corticosteroids for the glioblastoma condition. Corticosteroids included dexamethasone, methylprednisone, fortecortin, hydrocortisone, urbason, and prednisolone.
Outcome measures
| Measure |
Bevacizumab + Irinotecan
n=119 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=55 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Percentage of Participants Who Received Corticosteroid for Glioblastoma
|
80.0 percentage of participants
|
78.7 percentage of participants
|
SECONDARY outcome
Timeframe: From baseline until end of study (up to 4.5 years)Population: Data for this outcome measure were not collected as this outcome was removed as per changes in planned analysis.
Outcome measures
| Measure |
Bevacizumab + Irinotecan
n=116 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=55 Participants
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible.
|
|---|---|---|
|
Time to Treatment Failure
|
NA years
Data for time to treatment failure were not collected as this outcome was removed as per changes in planned analysis
|
NA years
Data for time to treatment failure were not collected as this outcome was removed as per changes in planned analysis
|
Adverse Events
Bevacizumab + Irinotecan
Serious events: 86 serious events
Other events: 107 other events
Deaths: 0 deaths
Temozolomide
Serious events: 46 serious events
Other events: 37 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bevacizumab + Irinotecan
n=119 participants at risk
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=55 participants at risk
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator or and, if eligible.
|
|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
1.7%
2/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
3.4%
4/119 • 4 years, 5 months,24 days
|
9.1%
5/55 • 4 years, 5 months,24 days
|
|
Cardiac disorders
Cardiovascular insufficiency
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Cardiac disorders
Restrictive cardiomyopathy
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Ear and labyrinth disorders
Otorrhoea
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Gastrointestinal disorders
Abdominal pain
|
0.84%
1/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Gastrointestinal disorders
Constipation
|
0.84%
1/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Gastrointestinal disorders
Diarrhoea
|
1.7%
2/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Gastrointestinal disorders
Diverticular perforation
|
1.7%
2/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Gastrointestinal disorders
Enteritis
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.84%
1/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Gastrointestinal disorders
Nausea
|
0.84%
1/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
General disorders
Chest pain
|
0.84%
1/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
General disorders
Gait disturbance
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
General disorders
General physical health deterioration
|
34.5%
41/119 • 4 years, 5 months,24 days
|
36.4%
20/55 • 4 years, 5 months,24 days
|
|
General disorders
Hernia
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
General disorders
Impaired healing
|
1.7%
2/119 • 4 years, 5 months,24 days
|
3.6%
2/55 • 4 years, 5 months,24 days
|
|
General disorders
Local swelling
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
General disorders
Multi-organ failure
|
0.00%
0/119 • 4 years, 5 months,24 days
|
3.6%
2/55 • 4 years, 5 months,24 days
|
|
General disorders
Oedema
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
General disorders
Pyrexia
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Immune system disorders
Contrast media allergy
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
Anal abscess
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
Aspergillus infection
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
Bone abscess
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
Brain abscess
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
Bronchitis
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
Cellulitis
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
extradural abscess
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
Infection
|
2.5%
3/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
Pneumonia
|
2.5%
3/119 • 4 years, 5 months,24 days
|
3.6%
2/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
Postoperative wound infection
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
Urosepsis
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Infections and infestations
Wound infection
|
2.5%
3/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Injury, poisoning and procedural complications
Fall
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Injury, poisoning and procedural complications
Laceration
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.84%
1/119 • 4 years, 5 months,24 days
|
5.5%
3/55 • 4 years, 5 months,24 days
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Injury, poisoning and procedural complications
Wound complication
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Investigations
General physical condition abnormal
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
1.7%
2/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.84%
1/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Musculoskeletal and connective tissue disorders
Tendon disorder
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to meninges
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Aphasia
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/119 • 4 years, 5 months,24 days
|
7.3%
4/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Cerebral cys
|
0.84%
1/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Cerebral haemorrhage
|
1.7%
2/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Cerebral infarction
|
1.7%
2/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Cerebrovascular accident
|
0.84%
1/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Coma
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Complex partial seizures
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Convulsion
|
14.3%
17/119 • 4 years, 5 months,24 days
|
16.4%
9/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Disturbance in attention
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Dizziness
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Epilepsy
|
5.0%
6/119 • 4 years, 5 months,24 days
|
10.9%
6/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Grand mal convulsion
|
4.2%
5/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Headache
|
1.7%
2/119 • 4 years, 5 months,24 days
|
7.3%
4/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Hemiparesis
|
0.84%
1/119 • 4 years, 5 months,24 days
|
7.3%
4/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Hemiplegia
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Hydrocephalus
|
0.84%
1/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Intracranial haematoma
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Intraventricular haemorrhage
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Myoclonus
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Neurological decompensation
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Partial seizures
|
1.7%
2/119 • 4 years, 5 months,24 days
|
5.5%
3/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Postictal paralysis
|
1.7%
2/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Status epilepticus
|
1.7%
2/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Subdural hygroma
|
0.84%
1/119 • 4 years, 5 months,24 days
|
3.6%
2/55 • 4 years, 5 months,24 days
|
|
Psychiatric disorders
Delirium
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Psychiatric disorders
Depression
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Psychiatric disorders
Mental disorder due to a general medical condition
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Psychiatric disorders
Panic attack
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Psychiatric disorders
Psychotic disorder
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Renal and urinary disorders
Cystitis glandularis
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Renal and urinary disorders
Nephrotic syndrome
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Renal and urinary disorders
Proteinuria
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Renal and urinary disorders
Renal failure acute
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary artery thrombosis
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.5%
3/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary fistula
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Surgical and medical procedures
Therapeutic procedure
|
0.00%
0/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Surgical and medical procedures
Tooth extraction
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Vascular disorders
Deep vein thrombosis
|
0.84%
1/119 • 4 years, 5 months,24 days
|
1.8%
1/55 • 4 years, 5 months,24 days
|
|
Vascular disorders
Embolism
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Vascular disorders
Hypertensive crisis
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Vascular disorders
Pelvic venous thrombosis
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Vascular disorders
Thrombophlebitis
|
0.84%
1/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
|
Vascular disorders
Thrombosis
|
1.7%
2/119 • 4 years, 5 months,24 days
|
0.00%
0/55 • 4 years, 5 months,24 days
|
Other adverse events
| Measure |
Bevacizumab + Irinotecan
n=119 participants at risk
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant.
|
Temozolomide
n=55 participants at risk
In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator or and, if eligible.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
45.4%
54/119 • 4 years, 5 months,24 days
|
14.5%
8/55 • 4 years, 5 months,24 days
|
|
Gastrointestinal disorders
Nausea
|
73.9%
88/119 • 4 years, 5 months,24 days
|
50.9%
28/55 • 4 years, 5 months,24 days
|
|
Nervous system disorders
Headache
|
50.4%
60/119 • 4 years, 5 months,24 days
|
40.0%
22/55 • 4 years, 5 months,24 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER