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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00369590
First received: August 24, 2006
Last updated: May 21, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Gliosarcoma
Adult Mixed Glioma
Recurrent Adult Brain Tumor
Biological: ziv-aflibercept
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Single Arm Trial of VEGF Trap in Patients With Recurrent Temozolomide-Resistant Malignant Gliomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival (PFS) at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Response rate associated with VEGF Trap therapy defined as proportions of patients experiencing complete or partial response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: August 2006
Study Completion Date: October 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Biological: ziv-aflibercept
Other Names:
  • aflibercept
  • vascular endothelial growth factor trap
  • VEGF Trap
  • Zaltrap

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • INR < = 1.5
  • Platelet count => 100,000/mm³
  • Hemoglobin => 10 g/dL (transfusion allowed)
  • SGOT/SGPT < = 2 times upper limit of normal (ULN)
  • Not pregnant or nursing
  • Negative pregnancy test
  • No previous 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 60-100%
  • Life expectancy = > 8 weeks
  • WBC = >3,000/mm³
  • Absolute neutrophil count = > 1,500/mm³
  • Bilirubin < = 2 times ULN
  • Creatinine < = 1.5 mg/dL OR creatinine clearance= > 60 mL/min
  • Urine protein:creatinine ratio < = 1 OR 24-hour urine protein < = 500 mg/dL
  • Fertile patients must use effective contraception prior to, during, and for = > 6 months after completion of study treatment
  • No significant medical illnesses that, in the opinion of the investigator, cannot be adequately controlled with appropriate therapy or would preclude compliance with study treatment
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to other agents used in the study
  • No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off of all therapy for that disease for = >3 years
  • At least 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin [radiosensitizer does not count])
  • At least 7 days since prior core biopsy
  • At least 28 days since prior investigational agents
  • No prior bevacizumab or vascular endothelial growth factor receptor inhibitors
  • No concurrent full-dose anticoagulants (e.g., warfarin or low molecular-weight heparin)
  • No clinically significant cardiovascular disease, including any of the following:

    • Cerebrovascular accident within the past 6 months
    • Uncontrolled hypertension, defined as blood pressure (BP) > 140/90 mm Hg or systolic BP > 180 mm Hg if diastolic BP < 90 mm Hg, on ≥ 2 repeated determinations on separate days within the past 3 months
    • Myocardial infarction, coronary artery bypass graft (CABG), or unstable angina pectoris within the past 6 months
    • New York Heart Association class III-IV congestive heart failure
    • No serious cardiac arrhythmia requiring medication
    • Clinically significant peripheral vascular disease within the past 6 months
    • Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months
    • No evidence of bleeding diathesis or coagulopathy
  • No more than 1 prior chemotherapy regimen (initial treatment and treatment for 1 relapse)
  • Surgical resection for relapsed disease with no anticancer therapy instituted for up to 12 weeks followed by another surgical resection is considered 1 relapse
  • If prior therapy for a grade 3 glioma was given, surgical diagnosis of a high-grade glioma is considered the first relapse
  • Prior surgical, interstitial brachytherapy, or stereotactic radiosurgery not considered prior therapy
  • If prior therapy included interstitial brachytherapy or stereotactic radiosurgery, must have confirmation of true progressive disease rather than radiation necrosis based upon either positron emission tomography (PET) scan, thallium scanning, MR spectroscopy, or surgical documentation of disease
  • Must show unequivocal radiographic evidence of tumor progression by MRI
  • Recent resection of recurrent or progressive tumor allowed
  • Residual disease not required
  • Temozolomide-resistant recurrent glioblastoma is defined as tumor progression or tumor recurrence during or after treatment with temozolomide-based chemotherapy regimens
  • Recovered from prior therapy
  • No other disease that would obscure toxicity or dangerously alter drug metabolism
  • No uncontrolled intercurrent illness, including, but not limited to, any of the following:

    • Ongoing or active infection
    • Psychiatric illness or social situations that would limit compliance with study requirements
    • No serious or nonhealing wound, ulcer, or bone fracture
    • No history of intracerebral or intratumoral hemorrhage
    • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
    • No significant traumatic injury within the past 28 days
  • At least 28 days since prior cytotoxic therapy
  • Histologically confirmed diagnosis of 1 of the following:

    • Intracranial glioblastoma or gliosarcoma
    • Anaplastic astrocytoma
    • Anaplastic oligodendroglioma
    • Anaplastic mixed oligoastrocytoma
    • Malignant astrocytoma not otherwise specified

      • NOTE: If original histology was grade 3 glioma, subsequent histological diagnosis of 1 of these diseases is allowed provided no prior diagnosis of grade 2 glioma
  • At least 20 unstained slides OR 1 tissue block available from original diagnostic biopsy/surgery or from biopsy/surgery at recurrence
  • Patients presenting at the time of first recurrence or relapse, defined as progression after initial therapy (i.e., radiotherapy +/- chemotherapy if that was used as initial therapy) are eligible
  • No other concurrent investigational drugs
  • No other concurrent investigational drugs
  • No concurrent cytotoxic or noncytotoxic therapy, including chemotherapy, radiotherapy, hormonal therapy, or immunotherapy
  • No concurrent major surgery
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • Concurrent anticonvulsant therapy allowed
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00369590

Locations
United States, California
University of California at Los Angeles (UCLA )
Los Angeles, California, United States, 90095
UCSF-Mount Zion
San Francisco, California, United States, 94115
United States, Maryland
Adult Brain Tumor Consortium
Baltimore, Maryland, United States, 21231-1000
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: John de Groot National Cancer Institute (NCI)
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00369590     History of Changes
Other Study ID Numbers: NCI-2009-00677, NCI-2009-00677, CDR0000495275, NABTC06-01, NABTC-06-01, U01CA062399
Study First Received: August 24, 2006
Last Updated: May 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Astrocytoma
Brain Neoplasms
Glioblastoma
Glioma
Oligodendroglioma
Gliosarcoma
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
Temozolomide
Endothelial Growth Factors
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 23, 2014