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Adult Anaplastic AstrocytomaPhase 2NCT00369590

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

A Phase 2 study testing ziv-aflibercept, pharmacological study and laboratory biomarker analysis in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by National Cancer Institute (NCI) at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ziv-aflibercept, pharmacological study and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
7 sitesUnited States
Study dates
Aug 2006to Oct 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 74Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • University of California Los Angeles

    Los Angeles, California, 90095

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

  • University of California San Francisco

    San Francisco, California, 94115

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
ziv-aflibercept, pharmacological study, laboratory biomarker analysis
Medical subject headings
Astrocytoma, Oligodendroglioma, Glioblastoma, Gliosarcoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ziv-afliberceptBiological

    Also called aflibercept, vascular endothelial growth factor trap, VEGF Trap, Zaltrap

    Given IV

  • pharmacological studyOther

    correlative studies

  • laboratory biomarker analysisOther

    correlative studies

Study groups in NCT00369590
Study groupRoleWhat they receive
All Study PatientsExperimentalPatients 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.
Receives: Biological: ziv-aflibercept; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 6 months

  2. 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.

    Measured: Start to End of treatment 39 cycles or 1yr 7.5months (78 weeks)

  3. Safety Profile - Events That Discontinued Treatment

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

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

Secondary outcomes (3)

  1. 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.

    Measured: Up to 2 years

  2. 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.

    Measured: up to 3 years

  3. Overall Survival

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

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Aug 2006 (estimated)
  2. Study startAug 2006
  3. Primary completionDec 2011
  4. Study completionOct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00369590
Sponsor's protocol ID
NCI-2009-00677
Other IDs
NCI-2009-00677, CDR0000495275, NABTC06-01, NABTC-06-01, U01CA062399
Status last verified
Aug 2015
First submitted
24 Aug 2006
Last updated
2 Oct 2015
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 21606416

  • 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.

    PubMed 21632852

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ziv-aflibercept, pharmacological study and laboratory biomarker analysis in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by National Cancer Institute (NCI) at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 74 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) at 6 Months (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00369590, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2015.

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