Epothilone ZK-219477 in Treating Patients With Recurrent Glioblastoma
Primary Purpose
Brain and Central Nervous System Tumors
Status
Completed
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
sagopilone
fluorescence in situ hybridization
gene expression analysis
immunohistochemistry staining method
laboratory biomarker analysis
pharmacological study
Sponsored by
About this trial
This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring adult glioblastoma, recurrent adult brain tumor, adult giant cell glioblastoma, adult gliosarcoma
Eligibility 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
Sites / Locations
- Centre Hospitalier Universitaire Vaudois
Outcomes
Primary Outcome Measures
Treatment success (complete or partial response or a progression-free survival at 6 months)
Secondary Outcome Measures
Objective response
Duration of response
Toxicity
Progression-free survival at 6 months
Overall survival at 6 and 12 months
Full Information
NCT ID
NCT00424060
First Posted
January 16, 2007
Last Updated
September 20, 2012
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
1. Study Identification
Unique Protocol Identification Number
NCT00424060
Brief Title
Epothilone ZK-219477 in Treating Patients With Recurrent Glioblastoma
Official Title
Phase II Study of ZK 219477 in Patients With Recurrent Glioblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2012
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
August 2007 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
4. Oversight
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors
Keywords
adult glioblastoma, recurrent adult brain tumor, adult giant cell glioblastoma, adult gliosarcoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
sagopilone
Intervention Type
Genetic
Intervention Name(s)
fluorescence in situ hybridization
Intervention Type
Genetic
Intervention Name(s)
gene expression analysis
Intervention Type
Other
Intervention Name(s)
immunohistochemistry staining method
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Type
Other
Intervention Name(s)
pharmacological study
Primary Outcome Measure Information:
Title
Treatment success (complete or partial response or a progression-free survival at 6 months)
Secondary Outcome Measure Information:
Title
Objective response
Title
Duration of response
Title
Toxicity
Title
Progression-free survival at 6 months
Title
Overall survival at 6 and 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roger Stupp, MD
Organizational Affiliation
Centre Hospitalier Universitaire Vaudois
Official's Role
Study Chair
Facility Information:
Facility Name
Centre Hospitalier Universitaire Vaudois
City
Lausanne
ZIP/Postal Code
CH-1011
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
21321091
Citation
Stupp R, Tosoni A, Bromberg JEC, Hau P, Campone M, Gijtenbeek J, Frenay M, Breimer L, Wiesinger H, Allgeier A, van den Bent MJ, Bogdahn U, van der Graaf W, Yun HJ, Gorlia T, Lacombe D, Brandes AA. Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group. Ann Oncol. 2011 Sep;22(9):2144-2149. doi: 10.1093/annonc/mdq729. Epub 2011 Feb 14.
Results Reference
result
Citation
Stupp R, Tosoni W, Taal W, et al.: Phase II trial of the epothilone analog sagopilone (ZK219477; ZK EPO) in patients with recurrent glioblastoma: initial report of the EORTC study 26061. [Abstract] J Clin Oncol 26 (Suppl 15): A-2015, 2008.
Results Reference
result
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Epothilone ZK-219477 in Treating Patients With Recurrent Glioblastoma
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