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AZD2171 in Treating Patients With Recurrent Glioblastoma Multiforme
This study has been completed.
First Received: March 21, 2006   Last Updated: December 6, 2008   History of Changes
Sponsors and Collaborators: Massachusetts General Hospital
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00305656
  Purpose

RATIONALE: AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well AZD2171 works in treating patients with recurrent glioblastoma multiforme.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: cediranib maleate
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Study of AZD2171 in Recurrent Glioblastoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression-free survival at 6 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment: 31
Study Start Date: December 2005
Detailed Description:

OBJECTIVES:

Primary

  • Determine the proportion of patients with recurrent glioblastoma multiforme (GM) who are alive and progression free 6 months after starting AZD2171 therapy.

Secondary

  • Assess the biological effect of AZD2171 by using the following MRI techniques: dynamic contrast-enhanced imaging; arterial spin-labeling imaging; perfusion-weighted imaging; and diffusion- tensor imaging at serial time points.
  • Measure circulating endothelial and progenitor cells and plasma levels of tumstatin, (vascular endothelial growth factor (VEGF)-A and -D, sVEGF receptors, P1GF, platelet-derived growth factor (PDGF)-AA, PDGF-AB, PDGF-BB, Ang1, thrombospondin-1, and interleukin-8 as markers for response to antiangiogenic therapy in recurrent GM.
  • Correlate treatment outcomes with pre-AZD2171 tumor specimens with respect to microvascular density, basement membrane and pericyte coverage, and angiopoietin-1 and -2 expression to determine whether these immunohistochemical analyses can be predictive of the response to AZD2171.
  • Measure polymorphisms of kdr/flk-1 gene and genetic analysis of HIF1-alpha, TP53, and endothelial nitric oxide synthase genes in the archival tumor specimens.
  • Determine the overall survival of patients with recurrent GM treated with AZD2171.
  • Determine the radiographic response rate in patients with recurrent GM treated with AZD2171.
  • Determine the safety of AZD2171 in this patient population.

OUTLINE: This is a multicenter study.

Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 12 months.

PROJECTED ACCRUAL: A total of 31 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed glioblastoma multiforme
  • Measurable contrast-enhancing tumor ≥ 1 cm in longest diameter by baseline MRI or CT scan

    • Patient must have been on no steroids OR a stable dose of steroids for ≥ 5 days prior to baseline MRI or CT scan

      • Patients who are on steroids must be maintained on a stable corticosteroid regimen from baseline scan until the start of study treatment
  • No intratumoral or peritumoral hemorrhage by MRI

PATIENT CHARACTERISTICS:

  • Karnofsky performance status ≥ 60%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other concurrent malignancy within the past 5 years except curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast
  • Mini-mental status examination score ≥ 15
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 8 g/dL
  • Bilirubin normal
  • AST/ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171
  • Mean QTc ≤ 470 msec (with Bazett's correction) on screening electrocardiogram
  • No history of familial long QT syndrome
  • No greater than +1 proteinuria on 2 consecutive dipsticks taken ≥ 1 week apart unless first urinalysis shows no protein
  • No uncontrolled intercurrent illness, including, but not limited to, any of the following:

    • Hypertension
    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • No known coagulopathy that increases the risk of bleeding
  • No history of clinically significant hemorrhages

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from toxicity of prior therapy
  • At least 3 months since prior radiation therapy, including cranial radiation therapy
  • At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
  • At least 3 weeks since prior molecularly-targeted agents
  • At least 4 weeks since prior major surgery
  • No more than 2 prior chemotherapy regimens or antineoplastic drugs
  • More than 30 days since prior participation in an investigational trial
  • At least 2 weeks since prior enzyme-inducing antiepileptic drugs (EIAEDs)
  • No concurrent EIAEDs

    • Concurrent non-EIAEDs allowed
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No concurrent vascular endothelial growth factor inhibitors

    • Prior thalidomide or lenolidomide allowed
  • No concurrent anticoagulants (e.g., warfarin) or antiplatelet agents including aspirin
  • No other concurrent anticancer agents or therapies
  • No concurrent grapefruit juice
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00305656

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Study Chair: Tracy Batchelor, MD, MPH Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000460079, MGH-05-254, NCI-7105
Study First Received: March 21, 2006
Last Updated: December 6, 2008
ClinicalTrials.gov Identifier: NCT00305656     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
adult glioblastoma
recurrent adult brain tumor
adult gliosarcoma
adult giant cell glioblastoma

Study placed in the following topic categories:
Glioblastoma
Astrocytoma
Central Nervous System Neoplasms
Recurrence
Brain Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Glioma
Glioblastoma Multiforme
Gliosarcoma
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Glioblastoma
Neoplasms by Histologic Type
Astrocytoma
Nervous System Diseases
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Neuroectodermal Tumors
Neoplasms
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Glioma
Neoplasms, Neuroepithelial
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on August 24, 2009