• Maximum tolerated dose [ Designated as safety issue: Yes ]
• Pharmacokinetics [ Designated as safety issue: No ]
• Response rate [ Designated as safety issue: No ]
• Toxicity [ Designated as safety issue: Yes ]
• Progression-free survival at 6 months [ Designated as safety issue: No ]
• Duration of progression-free survival [ Designated as safety issue: No ]
• Overall survival [ Designated as safety issue: No ]

• Maximum tolerated dose
• Pharmacokinetics
• Response rate
• Toxicity
• Progression-free survival at 6 months
• Duration of progression-free survival
• Overall survival

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I/II trial is studying the side effects and best dose of ixabepilone and how well it works in treating patients with recurrent glioma.

OBJECTIVES:

• Determine the maximum tolerated dose of ixabepilone in patients with recurrent high-grade glioma who are receiving or not receiving cytochrome P450-inducing anticonvulsants.
• Determine the pharmacokinetics of this drug in these patients.
• Determine the response rate of patients treated with this drug.
• Determine the toxicity of this drug in these patients.
• Determine the 6-month progression-free survival, duration of progression-free survival, and overall survival of patients treated with this drug.

OUTLINE: This is a phase I, dose-escalation, multicenter study followed by a phase II, safety and efficacy, multicenter study. For phase I only, patients are stratified according to cytochrome P450-inducing anticonvulsant use (yes vs no).

• Phase I: Patients receive ixabepilone IV over 1 hour on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3 patients receive escalating doses of ixabepilone until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 patients experience dose-limiting toxicity.

• Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A minimum of 10-15 patients will be accrued for the phase I portion of this study. A total of 22-33 patients will be accrued for the phase II portion of this study within 4-6 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant glioma

  • Anaplastic astrocytoma, glioblastoma multiforme, anaplastic oligodendroglioma, or anaplastic mixed glioma
  • Recurrent or progressive after radiotherapy with or without chemotherapy
  • Prior low-grade glioma that has progressed to high-grade glioma allowed
• Measurable disease by MRI or CT scan

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 9 g/dL

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST/ALT no greater than 2.5 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL

Other

• Mini mental score at least 15
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
• No concurrent serious infection or medical illness that would preclude study therapy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No more than 2 prior chemotherapy regimens
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 3 months since prior radiotherapy

Surgery

• Not specified

Other

• Recovered from prior therapy
• No other concurrent investigational agents

• No concurrent moderate to significant inhibitors of CYP3A4, including any of the following:

  • Clarithromycin
  • Erythromycin
  • Troleandomycin
  • Delaviridine
  • Nelfinavir
  • Amprenavir
  • Ritonavir
  • Indinavir
  • Saquinavir
  • Lopinavir
  • Itraconazole
  • Ketoconazole
  • Fluconazole (doses > 200 mg/day)
  • Voriconazole
  • Verapamil
  • Diltiazem
  • Amiodarone
  • Nefazodone
  • Fluoroxamine