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

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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)

Tracking Information
First Submitted Date  ICMJE August 24, 2006
First Posted Date  ICMJE August 29, 2006
Results First Submitted Date  ICMJE June 3, 2015
Results First Posted Date  ICMJE October 2, 2015
Last Update Posted Date October 2, 2015
Study Start Date  ICMJE August 2006
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2015)
  • Progression-free Survival (PFS) at 6 Months [ Time Frame: 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.
  • Safety Profile - Toxicities [ Time Frame: Start to End of treatment 39 cycles or 1yr 7.5months (78 weeks) ]
    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.
  • Safety Profile - Events That Discontinued Treatment [ Time Frame: Approximately 1 year (start of treatment - end of treatment) ]
    number of patients who experienced toxicity that led to being taken off treatment
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00369590 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 31, 2015)
  • Response Rate Associated With VEGF Trap Therapy Defined as Proportions of Patients Experiencing Complete or Partial Response [ Time Frame: Up to 2 years ]
    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.
  • Progression Free Survival (PFS) Rate for Subjects With Radiographic Response [ Time Frame: up to 3 years ]
    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.
  • Overall Survival [ Time Frame: 3 years ]
    all patients alive as of the last contact were censored for survival on the basis of that contact date
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE VEGF Trap in Treating Patients With Recurrent Malignant Gliomas That Did Not Respond to Temozolomide
Official Title  ICMJE Phase II Single Arm Trial of VEGF Trap in Patients With Recurrent Temozolomide-Resistant Malignant Gliomas
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adult Anaplastic Astrocytoma
  • Adult Anaplastic Oligodendroglioma
  • Adult Giant Cell Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
Intervention  ICMJE
  • Biological: ziv-aflibercept
    Given IV
    Other Names:
    • aflibercept
    • vascular endothelial growth factor trap
    • VEGF Trap
    • Zaltrap
  • Other: pharmacological study
    correlative studies
  • Other: laboratory biomarker analysis
    correlative studies
Study Arms  ICMJE Experimental: All Study Patients

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.

Interventions:
  • Biological: ziv-aflibercept
  • Other: pharmacological study
  • Other: laboratory biomarker analysis
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 31, 2015)
58
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE October 2012
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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%
  • Life expectancy = > 8 weeks
  • White blood count (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, Magnetic Resonance (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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00369590
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: John de Groot, MD M.D. Anderson Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP