AZD2171 in Treating Patients With Recurrent Glioblastoma Multiforme

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00305656
First received: March 21, 2006
Last updated: August 14, 2013
Last verified: July 2013
  Purpose

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


Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Drug: cediranib maleate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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:
  • Proportion of patients alive and progression-free at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiographic response proportion [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    Will be described with 95% confidence limits.

  • Overall survival [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    Will be described with 95% confidence limits.

  • Toxicity proportion [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
    Will be described with 95% confidence limits.


Enrollment: 31
Study Start Date: January 2006
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral AZD2171 once daily on days 1-28.
Drug: cediranib maleate
Given orally
Other Names:
  • AZD2171
  • Recentin

Detailed Description:

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

I. 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.

II. 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.

III. 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.

IV. 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.

V. Determine the overall survival of patients with recurrent GM treated with AZD2171.

VI. Determine the radiographic response rate in patients with recurrent GM treated with AZD2171.

VII. 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.

  Eligibility

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

Criteria:

  • AST/ALT =< 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance >= 60 mL/min
  • 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
  • Karnofsky performance status >= 60%
  • 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
  • Histologically confirmed glioblastoma multiforme
  • Platelet count >= 100,000/mm3
  • Hemoglobin >= 8 g/dL
  • Bilirubin normal
  • 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
  • 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
  • WBC >= 3,000/mm3
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Absolute neutrophil count >= 1,500/mm3
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00305656

Locations
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Investigators
Principal Investigator: Tracy Batchelor Massachusetts General Hospital
  More Information

Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00305656     History of Changes
Obsolete Identifiers: NCT00254943
Other Study ID Numbers: NCI-2009-00127, 05-254, N02CO12400, CDR0000460079
Study First Received: March 21, 2006
Last Updated: August 14, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Brain Neoplasms
Glioblastoma
Gliosarcoma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Maleic acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014