Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Glioma

Brain Neoplasms

Astrocytoma

Oligodendroglioma

Gliosarcoma

Disease Attributes

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Brain Tumor, Adult

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Aflibercept

Endothelial Growth Factors

Mitogens

Angiogenesis Inhibitors

Growth Inhibitors

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

pharmacological study

laboratory biomarker analysis

John de Groot, MD

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.

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

Phase II Single Arm Trial of VEGF Trap in Patients With Recurrent Temozolomide-Resistant Malignant Gliomas

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.

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.

number of patients who experienced toxicity that led to being taken off treatment

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.

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.

all patients alive as of the last contact were censored for survival on the basis of that contact date

National Cancer Institute (NCI)

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 Study Patients

Arm I - Anaplastic Glioma

Arm 2 - Glioblastoma

Total

Age, Continuous

Sex: Female, Male

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

Karnofsky Performance Status

Anaplastic astrocytoma

anaplastic oligodendroglioma

Anaplastic mixed oligoastrocytoma

Pathology

16 patients were anaplastic gliomas and 42 were glioblastomas all underwent central pathologic review

Stuart A Grossman, MD Director of ABTC

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

Progression-free Survival (PFS) at 6 Months

Complete Response

Partial Response

The 3 pts in Arm 2 were treated at 2nd recurrence and were excluded from final efficacy analysis

Response Rate Associated With VEGF Trap Therapy Defined as Proportions of Patients Experiencing Complete or Partial Response

Safety Profile - Toxicities

Safety Profile - Events That Discontinued Treatment

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.

Progression Free Survival (PFS) Rate for Subjects With Radiographic Response

Overall Survival

Overall Study

Spots Global Cancer Trial Database for VEGF Trap in Treating Patients With Recurrent Malignant Gliomas That Did Not Respond to Temozolomide

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial