Trial Outcomes & Findings for VEGF Trap in Treating Patients With Recurrent Malignant Gliomas That Did Not Respond to Temozolomide (NCT NCT00369590)
NCT ID: NCT00369590
Last Updated: 2015-10-02
Results Overview
This design yields 85% power to detect a true 30% 6-month PFS rate, while maintaining .91 probability of rejecting for a true 15% 6-month PFS rate. pts had MRIs at screening and at the 3rd and 5th cycles then every 8 weeks until progression. Response determined by modified MacDonald Criteria Complete Response (CR): Complete disappearance of all measurable and evaluable disease, no new lesions. no steroids Partial Response (PR): Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable lesions. no new lesions. steroid dose no \> than maximum dose used in first 8 weeks of treatment. Stable: Does not qualify for CR, PR, or progression steroid dose no \> than maximum dose used in first 8 weeks of treatment. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no increase) Clear clinical worsening.
COMPLETED
PHASE2
58 participants
6 months
2015-10-02
Participant Flow
Patients (pts) were enrolled from Feb 2007 - Nov 2008. pts were from seven different cancer centers and were recruited from their outpatient cancer centers.
Participant milestones
| Measure |
Arm I - Anaplastic Glioma
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
Arm 2 - Glioblastoma
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
42
|
|
Overall Study
COMPLETED
|
16
|
42
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
VEGF Trap in Treating Patients With Recurrent Malignant Gliomas That Did Not Respond to Temozolomide
Baseline characteristics by cohort
| Measure |
Arm I - Anaplastic Glioma
n=16 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
Arm 2 - Glioblastoma
n=42 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
Total
n=58 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53 years
n=5 Participants
|
55 years
n=7 Participants
|
54 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Karnofsky Performance Status
|
90 units on a scale
n=5 Participants
|
90 units on a scale
n=7 Participants
|
90 units on a scale
n=5 Participants
|
|
Pathology
Glioblastoma
|
0 participants
n=5 Participants
|
39 participants
n=7 Participants
|
39 participants
n=5 Participants
|
|
Pathology
Gliosarcoma
|
0 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Pathology
Anaplastic astrocytoma
|
12 participants
n=5 Participants
|
0 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Pathology
anaplastic oligodendroglioma
|
3 participants
n=5 Participants
|
0 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Pathology
Anaplastic mixed oligoastrocytoma
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: pts not known to be progression free at time of the 6-month scan (24weeks) were considered to experienced treatment failure. If at least 10pts (24%) are progression-frree at 6months (GBM) the agent will be considered promising for futher study. The 3 pts in Arm 2 were treated at 2nd recurrence and were excluded from final efficacy analysis
This design yields 85% power to detect a true 30% 6-month PFS rate, while maintaining .91 probability of rejecting for a true 15% 6-month PFS rate. pts had MRIs at screening and at the 3rd and 5th cycles then every 8 weeks until progression. Response determined by modified MacDonald Criteria Complete Response (CR): Complete disappearance of all measurable and evaluable disease, no new lesions. no steroids Partial Response (PR): Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable lesions. no new lesions. steroid dose no \> than maximum dose used in first 8 weeks of treatment. Stable: Does not qualify for CR, PR, or progression steroid dose no \> than maximum dose used in first 8 weeks of treatment. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no increase) Clear clinical worsening.
Outcome measures
| Measure |
Arm I - Anaplastic Glioma
n=16 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
Arm 2 - Glioblastoma
n=39 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
|---|---|---|
|
Progression-free Survival (PFS) at 6 Months
|
25 percentage of participants
|
7.7 percentage of participants
|
PRIMARY outcome
Timeframe: Start to End of treatment 39 cycles or 1yr 7.5months (78 weeks)number of cycles patient was able to have before developing a toxicity that required removing the patient from treatment. Treatment: Aflibercept 4mg/kg intravenously on day 1 of every 14-day cycle - 2 week cycle.
Outcome measures
| Measure |
Arm I - Anaplastic Glioma
n=16 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
Arm 2 - Glioblastoma
n=42 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
|---|---|---|
|
Safety Profile - Toxicities
|
5 cycles
Interval 1.0 to 39.0
|
3.5 cycles
Interval 0.0 to 8.0
|
PRIMARY outcome
Timeframe: Approximately 1 year (start of treatment - end of treatment)number of patients who experienced toxicity that led to being taken off treatment
Outcome measures
| Measure |
Arm I - Anaplastic Glioma
n=16 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
Arm 2 - Glioblastoma
n=42 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
|---|---|---|
|
Safety Profile - Events That Discontinued Treatment
|
8 participants
|
6 participants
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: The 3 pts in Arm 2 were treated at 2nd recurrence and were excluded from final efficacy analysis
pts had MRIs at screening and at the 3rd and 5th cycles then every 8 weeks until progression. All responders were centrally reviewed for confirmation Response determined by modified MacDonald Criteria Complete Response (CR): Complete disappearance of all measurable and evaluable disease, no new lesions. no steroids Partial Response (PR): Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable lesions. no new lesions. steroid dose no \> than maximum dose used in first 8 weeks of treatment. Stable: Does not qualify for CR, PR, or progression steroid dose no \> than maximum dose used in first 8 weeks of treatment. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no increase) Clear clinical worsening.
Outcome measures
| Measure |
Arm I - Anaplastic Glioma
n=16 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
Arm 2 - Glioblastoma
n=39 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
|---|---|---|
|
Response Rate Associated With VEGF Trap Therapy Defined as Proportions of Patients Experiencing Complete or Partial Response
Complete Response
|
1 participants
|
0 participants
|
|
Response Rate Associated With VEGF Trap Therapy Defined as Proportions of Patients Experiencing Complete or Partial Response
Partial Response
|
6 participants
|
7 participants
|
SECONDARY outcome
Timeframe: up to 3 yearsPopulation: Arm1 had total of 7 pts with response however, 2 pts stopped treatment early and were censored at 6 and 10 weeks. Arm 2 had total to 7 pts with response however 1 pt stopped treatment after 2 weeks but had a 4 week scan showing PR. - pt was censored.
pts with confirmed radiographic response and their rate of progression (PFS). Response determined by modified MacDonald Criteria Complete Response (CR): Complete disappearance of all measurable and evaluable disease, no new lesions. no steroids Partial Response (PR): Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable lesions. no new lesions. steroid dose no \> than maximum dose used in first 8 weeks of treatment. Stable: Does not qualify for CR, PR, or progression steroid dose no \> than maximum dose used in first 8 weeks of treatment. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no increase) Clear clinical worsening.
Outcome measures
| Measure |
Arm I - Anaplastic Glioma
n=5 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
Arm 2 - Glioblastoma
n=6 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
|---|---|---|
|
Progression Free Survival (PFS) Rate for Subjects With Radiographic Response
|
45 weeks
Interval 24.0 to 134.0
|
23 weeks
Interval 15.0 to 65.0
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: The 3 pts in Arm 2 were treated at 2nd recurrence and were excluded from final efficacy analysis
all patients alive as of the last contact were censored for survival on the basis of that contact date
Outcome measures
| Measure |
Arm I - Anaplastic Glioma
n=16 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
Arm 2 - Glioblastoma
n=39 Participants
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
|---|---|---|
|
Overall Survival
|
55 weeks
Interval 16.0 to 128.0
|
39 weeks
Interval 3.0 to 150.0
|
Adverse Events
All Study Patients
Serious adverse events
| Measure |
All Study Patients
n=58 participants at risk
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
|---|---|
|
Nervous system disorders
ischemia cerebrovascular
|
3.4%
2/58 • Number of events 2 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Gastrointestinal disorders
Oral hemorrhage
|
1.7%
1/58 • Number of events 1 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
Other adverse events
| Measure |
All Study Patients
n=58 participants at risk
Patients receive VEGF Trap (ziv-aflibercept) IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study; laboratory biomarker analysis.
ziv-aflibercept: Given IV
pharmacological study: correlative studies
laboratory biomarker analysis: correlative studies
|
|---|---|
|
Nervous system disorders
ataxia
|
1.7%
1/58 • Number of events 1 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Psychiatric disorders
confusion
|
1.7%
1/58 • Number of events 1 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Nervous system disorders
dysphaia
|
1.7%
1/58 • Number of events 1 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
General disorders
fatigue
|
5.2%
3/58 • Number of events 3 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Skin and subcutaneous tissue disorders
palmar-plantar erythrodysesthesia syndrom
|
1.7%
1/58 • Number of events 1 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Nervous system disorders
headache
|
1.7%
1/58 • Number of events 1 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Vascular disorders
hypertension
|
10.3%
6/58 • Number of events 6 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Metabolism and nutrition disorders
hyponatremia
|
3.4%
2/58 • Number of events 2 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Metabolism and nutrition disorders
hypophosphatejia
|
3.4%
2/58 • Number of events 2 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Respiratory, thoracic and mediastinal disorders
hypoxia
|
1.7%
1/58 • Number of events 1 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Investigations
Aspartate aminotransferase increase
|
1.7%
1/58 • Number of events 1 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Investigations
lymphopenia
|
6.9%
4/58 • Number of events 4 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Gastrointestinal disorders
Mucositis oral
|
3.4%
2/58 • Number of events 2 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Investigations
Neutrophil count decrease
|
1.7%
1/58 • Number of events 1 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
General disorders
pain
|
3.4%
2/58 • Number of events 2 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Cardiac disorders
pericarditis
|
1.7%
1/58 • Number of events 1 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Renal and urinary disorders
proteinuria
|
3.4%
2/58 • Number of events 2 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Skin and subcutaneous tissue disorders
rash
|
1.7%
1/58 • Number of events 1 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Vascular disorders
thromboembolic event
|
3.4%
2/58 • Number of events 2 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
|
Injury, poisoning and procedural complications
wound complication
|
1.7%
1/58 • Number of events 1 • adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
|
Additional Information
Stuart A Grossman, MD Director of ABTC
Adult Brain Tumor Consortium
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60