This phase II trial is studying how well VEGF Trap works in treating patients with recurrent malignant or anaplastic gliomas that did not respond to temozolomide. VEGF Trap may stop the growth of malignant or anaplastic gliomas by blocking blood flow to the tumor.
PRIMARY OBJECTIVES: I. Determine the therapeutic efficacy of VEGF Trap in patients with temozolomide-resistant malignant gliomas at first recurrence as measured by 6-month progression-free survival (PFS). II. Determine the safety profile of VEGF Trap in these patients. SECONDARY OBJECTIVES: I. Determine the efficacy of this regimen as measured by radiographic response, PFS, time to progression, and overall survival. II. Characterize the single-dose and repeated-dose pharmacokinetic profiles of VEGF Trap in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to histology (glioblastoma vs anaplastic glioma). Patients receive VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
58
University of California Los Angeles
Los Angeles, California, United States
University of California San Francisco
San Francisco, California, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Progression-free Survival (PFS) at 6 Months
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
Safety Profile - Toxicities
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)
Safety Profile - Events That Discontinued Treatment
number of patients who experienced toxicity that led to being taken off treatment
Time frame: Approximately 1 year (start of treatment - end of treatment)
Response Rate Associated With VEGF Trap Therapy Defined as Proportions of Patients Experiencing Complete or Partial Response
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.
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University of Pittsburgh
Pittsburgh, Pennsylvania, United States
M D Anderson Cancer Center
Houston, Texas, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Time frame: Up to 2 years
Progression Free Survival (PFS) Rate for Subjects With Radiographic Response
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
Overall Survival
all patients alive as of the last contact were censored for survival on the basis of that contact date
Time frame: 3 years