Epothilone ZK-219477 in Treating Patients With Recurrent Glioblastoma

NCT ID: NCT00424060

Last Updated: 2012-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma; recurrent adult brain tumor; adult giant cell glioblastoma; adult gliosarcoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

sagopilone

Intervention Type: DRUG

fluorescence in situ hybridization

Intervention Type: GENETIC

gene expression analysis

Intervention Type: GENETIC

immunohistochemistry staining method

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roger Stupp, MD

Role: STUDY_CHAIR

Centre Hospitalier Universitaire Vaudois

Locations

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Countries

Switzerland

References

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.

Reference Type: RESULT

PMID: 21321091 (View on PubMed)

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.

Reference Type: RESULT

Other Identifiers

EORTC-26061

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2006-001659-37

Identifier Type: -

Identifier Source: secondary_id

SPRI-EORTC-26061

Identifier Type: -

Identifier Source: secondary_id

EORTC-26061

Identifier Type: -

Identifier Source: org_study_id