Epothilone ZK-219477 in Treating Patients With Recurrent Glioblastoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00424060
First received: January 16, 2007
Last updated: September 20, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
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
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of ZK 219477 in Patients With Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Treatment success (complete or partial response or a progression-free survival at 6 months) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Progression-free survival at 6 months [ Designated as safety issue: No ]
  • Overall survival at 6 and 12 months [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: December 2006
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

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

Secondary

  • 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.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00424060

Locations
Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Roger Stupp, MD Centre Hospitalier Universitaire Vaudois
  More Information

Additional Information:
Publications:
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00424060     History of Changes
Other Study ID Numbers: EORTC-26061, EORTC-26061, EUDRACT-2006-001659-37, SPRI-EORTC-26061
Study First Received: January 16, 2007
Last Updated: September 20, 2012
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
adult glioblastoma
recurrent adult brain tumor
adult giant cell glioblastoma
adult gliosarcoma

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

ClinicalTrials.gov processed this record on October 22, 2014