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Phase II Study of ZK 219477 in Patients With Recurrent Glioblastoma

Phase 2
18 Years
Not Enrolling
Brain and Central Nervous System Tumors

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Trial Information

Phase II Study of ZK 219477 in Patients With Recurrent Glioblastoma



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


- 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.

Inclusion Criteria


- Histologically confirmed glioblastoma

- Presence of oligodendroglial elements allowed provided they make up < 25% of

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Treatment success (complete or partial response or a progression-free survival at 6 months)

Safety Issue:


Principal Investigator

Roger Stupp, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Centre Hospitalier Universitaire Vaudois


United States: Federal Government

Study ID:




Start Date:

December 2006

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult glioblastoma
  • recurrent adult brain tumor
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • Glioblastoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms