ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 41 of 228 for:    "Anaplastic oligodendroglioma"

VEGF Trap in Treating Patients With Recurrent Malignant Gliomas That Did Not Respond to Temozolomide

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00369590
Recruitment Status : Completed
First Posted : August 29, 2006
Results First Posted : October 2, 2015
Last Update Posted : October 2, 2015
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Interventions Biological: ziv-aflibercept
Other: pharmacological study
Other: laboratory biomarker analysis
Enrollment 58
Recruitment Details Patients (pts) were enrolled from Feb 2007 - Nov 2008. pts were from seven different cancer centers and were recruited from their outpatient cancer centers.
Pre-assignment Details  
Arm/Group Title Arm I - Anaplastic Glioma Arm 2 - Glioblastoma
Hide Arm/Group Description

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

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

Period Title: Overall Study
Started 16 42
Completed 16 42
Not Completed 0 0
Arm/Group Title Arm I - Anaplastic Glioma Arm 2 - Glioblastoma Total
Hide Arm/Group Description

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

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 of all reporting groups
Overall Number of Baseline Participants 16 42 58
Hide Baseline Analysis Population Description
16 patients were anaplastic gliomas and 42 were glioblastomas all underwent central pathologic review
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 16 participants 42 participants 58 participants
53
(26 to 70)
55
(33 to 72)
54
(26 to 72)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 42 participants 58 participants
Female
5
  31.3%
25
  59.5%
30
  51.7%
Male
11
  68.8%
17
  40.5%
28
  48.3%
Karnofsky Performance Status   [1] 
Median (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 16 participants 42 participants 58 participants
90
(60 to 100)
90
(60 to 100)
90
(60 to 100)
[1]
Measure Description:

The Karnofsky Performance Scale Index allows patients to be classified as to their functional impairment.

100-80: Able to carry on normal activity and to work; No special care needed.

70-50: Unable to work; able to live at home and care for most personal needs; varying amount of assistance needed

40-10: Unable to care for self; Requires equivalent of institutional or hospital care; diseases may be progressing rapidly.

0: Dead

Pathology  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants 42 participants 58 participants
Glioblastoma 0 39 39
Gliosarcoma 0 3 3
Anaplastic astrocytoma 12 0 12
anaplastic oligodendroglioma 3 0 3
Anaplastic mixed oligoastrocytoma 1 0 1
1.Primary Outcome
Title Progression-free Survival (PFS) at 6 Months
Hide Description

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.

Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

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

Arm/Group Title Arm I - Anaplastic Glioma Arm 2 - Glioblastoma
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 16 39
Measure Type: Number
Unit of Measure: percentage of participants
25 7.7
2.Primary Outcome
Title Safety Profile - Toxicities
Hide Description 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.
Time Frame Start to End of treatment 39 cycles or 1yr 7.5months (78 weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I - Anaplastic Glioma Arm 2 - Glioblastoma
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 16 42
Median (Full Range)
Unit of Measure: cycles
5
(1 to 39)
3.5
(0 to 8)
3.Primary Outcome
Title Safety Profile - Events That Discontinued Treatment
Hide Description number of patients who experienced toxicity that led to being taken off treatment
Time Frame Approximately 1 year (start of treatment - end of treatment)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I - Anaplastic Glioma Arm 2 - Glioblastoma
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 16 42
Measure Type: Number
Unit of Measure: participants
8 6
4.Secondary Outcome
Title Response Rate Associated With VEGF Trap Therapy Defined as Proportions of Patients Experiencing Complete or Partial Response
Hide Description

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.

Time Frame Up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The 3 pts in Arm 2 were treated at 2nd recurrence and were excluded from final efficacy analysis
Arm/Group Title Arm I - Anaplastic Glioma Arm 2 - Glioblastoma
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 16 39
Measure Type: Number
Unit of Measure: participants
Complete Response 1 0
Partial Response 6 7
5.Secondary Outcome
Title Progression Free Survival (PFS) Rate for Subjects With Radiographic Response
Hide Description

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.

Time Frame up to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

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.

Arm/Group Title Arm I - Anaplastic Glioma Arm 2 - Glioblastoma
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 5 6
Median (95% Confidence Interval)
Unit of Measure: weeks
45
(24 to 134)
23
(15 to 65)
6.Secondary Outcome
Title Overall Survival
Hide Description all patients alive as of the last contact were censored for survival on the basis of that contact date
Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The 3 pts in Arm 2 were treated at 2nd recurrence and were excluded from final efficacy analysis
Arm/Group Title Arm I - Anaplastic Glioma Arm 2 - Glioblastoma
Hide Arm/Group Description:

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

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 Number of Participants Analyzed 16 39
Median (Full Range)
Unit of Measure: weeks
55
(16 to 128)
39
(3 to 150)
Time Frame adverse events were collected at baseline and at the end of each cycle until taken off treatment, approximately 1 yr
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title All Study Patients
Hide Arm/Group Description

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

All-Cause Mortality
All Study Patients
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
All Study Patients
Affected / at Risk (%) # Events
Total   3/58 (5.17%)    
Gastrointestinal disorders   
Oral hemorrhage * 1 [1]  1/58 (1.72%)  1
Nervous system disorders   
ischemia cerebrovascular * 1  2/58 (3.45%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
systemic hemorrhage
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
All Study Patients
Affected / at Risk (%) # Events
Total   35/58 (60.34%)    
Cardiac disorders   
pericarditis * 1  1/58 (1.72%)  1
Gastrointestinal disorders   
Mucositis oral * 1  2/58 (3.45%)  2
General disorders   
fatigue * 1  3/58 (5.17%)  3
pain * 1  2/58 (3.45%)  2
Injury, poisoning and procedural complications   
wound complication * 1  1/58 (1.72%)  1
Investigations   
Aspartate aminotransferase increase * 1  1/58 (1.72%)  1
lymphopenia * 1  4/58 (6.90%)  4
Neutrophil count decrease * 1  1/58 (1.72%)  1
Metabolism and nutrition disorders   
hyponatremia * 1  2/58 (3.45%)  2
hypophosphatejia * 1  2/58 (3.45%)  2
Nervous system disorders   
ataxia * 1  1/58 (1.72%)  1
dysphaia * 1  1/58 (1.72%)  1
headache * 1  1/58 (1.72%)  1
Psychiatric disorders   
confusion * 1  1/58 (1.72%)  1
Renal and urinary disorders   
proteinuria * 1  2/58 (3.45%)  2
Respiratory, thoracic and mediastinal disorders   
hypoxia * 1  1/58 (1.72%)  1
Skin and subcutaneous tissue disorders   
palmar-plantar erythrodysesthesia syndrom * 1 [1]  1/58 (1.72%)  1
rash * 1  1/58 (1.72%)  1
Vascular disorders   
hypertension * 1  6/58 (10.34%)  6
thromboembolic event * 1 [2]  2/58 (3.45%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
hand-foot syndrome
[2]
Thrombosis/embolism
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Stuart A Grossman, MD Director of ABTC
Organization: Adult Brain Tumor Consortium
Phone: 410-955-8837
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00369590     History of Changes
Other Study ID Numbers: NCI-2009-00677
NCI-2009-00677 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000495275
NABTC06-01 ( Other Identifier: Adult Brain Tumor Consortium )
NABTC-06-01 ( Other Identifier: CTEP )
U01CA062399 ( U.S. NIH Grant/Contract )
First Submitted: August 24, 2006
First Posted: August 29, 2006
Results First Submitted: June 3, 2015
Results First Posted: October 2, 2015
Last Update Posted: October 2, 2015