Epothilone ZK-219477 in Treating Patients With Recurrent Glioblastoma

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