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

NCT00369590 | Completed Phase 2 Results DMC

• 5 other identifiers: NCI-2009-00677CDR0000495275NABTC06-01NABTC-06-01U01CA062399
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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

  Approximately 1 year (start of treatment - end of treatment)

Secondary Outcomes (3)

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

  Up to 2 years

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

  up to 3 years

• Overall Survival

  3 years

Study Arms (1)

All Study Patients

EXPERIMENTAL

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.

Biological: ziv-aflibercept; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

ziv-aflibercept BIOLOGICAL

Given IV

Also known as: aflibercept, vascular endothelial growth factor trap, VEGF Trap, Zaltrap

All Study Patients

pharmacological study OTHER

correlative studies

All Study Patients

laboratory biomarker analysis OTHER

correlative studies

All Study Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• International Normalized Ratio (INR) \< = 1.5
• Platelet count =\> 100,000/mm³
• Hemoglobin =\> 10 g/dL (transfusion allowed)
• Serum glutamic oxaloacetic transaminase (SGOT)/Serum glutamic pyruvic transaminase (SGPT) \< = 2 times upper limit of normal (ULN)
• Not pregnant or nursing
• Negative pregnancy test
• No previous Vascular endothelial growth factor (VEGF) Trap
• At least 4 weeks since chemotherapy, surgery, or open biopsy
• At least 2 weeks since vincristine
• At least 6 weeks since carmustine, lomustine, fotemustine, or radiation therapy
• At least 42 days since prior nitrosoureas
• At least 3 weeks since procarbazine
• No previous Gliadel wafers or bevacizumab
• Tumor did not respond to previous radiation therapy and temozolomide
• Karnofsky performance status (KPS) 60-100%

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

University of California San Francisco

San Francisco, California, 94115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (2)

• de Groot JF, Lamborn KR, Chang SM, Gilbert MR, Cloughesy TF, Aldape K, Yao J, Jackson EF, Lieberman F, Robins HI, Mehta MP, Lassman AB, Deangelis LM, Yung WK, Chen A, Prados MD, Wen PY. Phase II study of aflibercept in recurrent malignant glioma: a North American Brain Tumor Consortium study. J Clin Oncol. 2011 Jul 1;29(19):2689-95. doi: 10.1200/JCO.2010.34.1636. Epub 2011 May 23.

  PMID: 21606416 BACKGROUND

• de Groot JF, Piao Y, Tran H, Gilbert M, Wu HK, Liu J, Bekele BN, Cloughesy T, Mehta M, Robins HI, Lassman A, DeAngelis L, Camphausen K, Chen A, Yung WK, Prados M, Wen PY, Heymach JV. Myeloid biomarkers associated with glioblastoma response to anti-VEGF therapy with aflibercept. Clin Cancer Res. 2011 Jul 15;17(14):4872-81. doi: 10.1158/1078-0432.CCR-11-0271. Epub 2011 Jun 1.

  PMID: 21632852 DERIVED

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma; Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Stuart A Grossman, MD Director of ABTC
• Organization: Adult Brain Tumor Consortium

grossman@jhmi.edu

410-955-8837

Study Officials

• John de Groot, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2006
• First Posted: August 29, 2006
• Study Start: August 1, 2006
• Primary Completion: December 1, 2011
• Study Completion: October 1, 2012
• Last Updated: October 2, 2015
• Results First Posted: October 2, 2015

Record last verified: 2015-08

Locations

US (7)