Epothilone ZK-219477 in Treating Patients With Recurrent Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00424060
Recruitment Status : Completed
First Posted : January 18, 2007
Last Update Posted : September 24, 2012
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

January 16, 2007
January 18, 2007
September 24, 2012
December 2006
August 2007   (Final data collection date for primary outcome measure)
Treatment success (complete or partial response or a progression-free survival at 6 months)
Treatment success (complete or partial response)
Complete list of historical versions of study NCT00424060 on Archive Site
  • Objective response
  • Duration of response
  • Toxicity
  • Progression-free survival at 6 months
  • Overall survival at 6 and 12 months
Same as current
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Epothilone ZK-219477 in Treating Patients With Recurrent Glioblastoma
Phase II Study of ZK 219477 in Patients With Recurrent Glioblastoma

RATIONALE: Drugs used in chemotherapy, such as epothilone ZK-219477, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well epothilone ZK-219477 works in treating patients with recurrent glioblastoma.



  • Assess the therapeutic activity of epothilone ZK-219477 in patients with recurrent glioblastoma.


  • Determine the safety profile, mechanism of action, and pharmacokinetics of this drug in these patients.
  • Gather information about the biological characteristics of the patients' tumor that may provide information on response or resistance to this drug.

OUTLINE: This is a nonrandomized, open-label, multicenter study.

Patients receive epothilone ZK-219477 IV over 3 hours on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline for biomarker analysis and for comparison of genetic alterations in tumor tissue with germline DNA. Blood samples are also collected periodically during course 1 for pharmacokinetic studies. Tumor tissue obtained at diagnosis, and possibly recurrence, is used for immunohistochemical analyses for biomarkers. Fluorescent in situ hybridization (FISH) is used to detect genetic alterations and gene expression.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Phase 2
Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Brain and Central Nervous System Tumors
  • Drug: sagopilone
  • Genetic: fluorescence in situ hybridization
  • Genetic: gene expression analysis
  • Other: immunohistochemistry staining method
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Not Provided
August 2007   (Final data collection date for primary outcome measure)


  • Histologically confirmed glioblastoma

    • Presence of oligodendroglial elements allowed provided they make up < 25% of tumor
  • Measurable disease, defined as ≥ 1 bidimensionally measurable target lesion with a largest diameter of ≥ 2 cm by MRI within the past 2 weeks
  • Recurrent disease

    • Documented by MRI after failing prior therapy (usually standard radiotherapy with concurrent and maintenance temozolomide)
    • Subsequent histologic confirmation of recurrence required for patients who received prior high-dose radiotherapy (> 65 Gy), stereotactic radiosurgery, or internal radiotherapy
  • Multifocal disease that is not amenable to radiotherapy allowed provided the patient received no more than 1 line of prior chemotherapy


  • WHO performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • AST and ALT < 2.5 times ULN
  • Alkaline phosphatase < 2.5 times ULN
  • Creatinine < 1.5 times ULN
  • Clinically normal cardiac function
  • No ischemic heart disease within the past 12 months

    • Stable ischemic heart disease (e.g., treated angina that is stable under appropriate therapy) allowed
  • No New York Heart Association class III or IV cardiac insufficiency
  • No unstable angina
  • No arrhythmia
  • No psychological, familial, sociological, or geographical factors that would preclude study compliance
  • No other malignancy except cone-biopsied carcinoma of the cervix or adequately treated basal cell or squamous cell skin cancer
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile female patients must use effective contraception during and for 3 months after completion of study treatment
  • Fertile male patients must use effective contraception during and for 6 months after completion of study treatment


  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
  • More than 3 months since prior radiotherapy to the brain
  • More than 3 months since prior surgery for recurrent primary brain tumor unless 1 of the following criteria are met:

    • Measurable residual disease documented by immediate (within 72 hours) postoperative imaging
    • Evidence of a progressive and measurable target lesion found at postoperative follow-up
    • Presence of a second measurable target lesion outside the surgical area
  • Prior adjuvant temozolomide as first-line therapy allowed
  • No prior chemotherapy for recurrent glioblastoma

    • One prior chemotherapy regimen given as adjuvant therapy allowed
  • Concurrent corticosteroids allowed provided dose is stable or decreasing for ≥ 1 week
  • No concurrent phenytoin, carbamazepine, or phenobarbital
  • No concurrent Hypericum perforatum (St. John's wort)
  • No concurrent enzyme-inducing antiepileptic drugs (EIAEDs)

    • Patients on EIAEDs should have been switched to non-EIAEDs with a wash-out period of ≥ 1 month
  • No other concurrent anticancer agents (except alternative or homeopathic medicine)
  • No other concurrent investigational treatment
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
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European Organisation for Research and Treatment of Cancer - EORTC
European Organisation for Research and Treatment of Cancer - EORTC
Not Provided
Study Chair: Roger Stupp, MD Centre Hospitalier Universitaire Vaudois
European Organisation for Research and Treatment of Cancer - EORTC
September 2012

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