Clinical Trial Finder

Inclusion Criteria:

• - Patients must have histologically proven malignant glioma (anaplastic astrocytoma or glioblastoma multiforme) which is progressive or recurrent following radiation therapy +/- chemotherapy; patients with previous low grade glioma who progressed after radiotherapy +/- chemotherapy and are biopsied and found to have a high grade glioma are eligible.

• - Patients must have measurable progressive or recurrent malignant glioma by MRI or CT imaging.

• - Patients must have recovered from severe toxicity of prior therapy; an interval of at least 3 months must have elapsed since the completion of the most recent course of radiation therapy while at least 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen and at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen.

• - Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others) - Absolute neutrophil count >= 1500/mm^3.

• - Platelets >= 100,000/mm^3.

• - HgB > 9 g/dl.

• - Creatinine =< 1.5mg/dl.

• - Total Bilirubin =< 1.5mg/dl.

• - Transaminases =< 2.5 times above the upper limits of the institutional norm) - Patients must be able to provide written informed consent.

• - Patients must have =< 2 prior chemotherapy regimens.

• - Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; the anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant; female patients of child-bearing potential must have a negative pregnancy test.

• - Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast; patients with prior malignancies must be disease-free for >= five years.

• - Patients must be maintained on a stable corticosteroid regimen from the time of their baseline scan until the start of treatment.

• - Patients must have a Mini Mental State Exam score of >= 15.

Exclusion Criteria:

• - Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.

• - Patients who are pregnant or breast-feeding.

• - Patients with more than 2 prior chemotherapy regimens.

• - Patients receiving concurrent investigational agents.

• - Patients receiving any of the following medications which are known to be moderate to significant inhibitors of CYP3A4 are not eligible: - Antibiotics: clarithromycin, erythromycin, troleandomycin.

• - Anti-HIV agents: delavirdine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir.

• - Antifungals: itraconazole, ketoconazole, fluconazole (doses > 200mg/day), voriconazole.

• - Antidepressants: nefazodone, fluvoxamine.

• - Calcium channel blockers: verapamil, diltiazem.

- Miscellaneous: amiodarone NOTE: The above list of agents was provided by the National Cancer Institute as moderate to significant inhibitors of CYP3A4 that should not be administered with BMS; there may be other agents that have similar activities on CYP3A4, however these are currently unspecified; if investigators are concerned about a particular medication's inhibitory effect on CYP3A4, they are encouraged to consult local pharmacy services for more information and to contact the principal investigator to discuss the situation further

PRIMARY OBJECTIVES:

• I. To determine the maximum tolerated dose of BMS-247550 when administered to adults with recurrent malignant gliomas, receiving (Group A) or not receiving (Group B) anticonvulsants known to be metabolized by the P450 hepatic enzyme complex.

• II. To describe the pharmacokinetics of this route of administration, measuring BMS-247550, and determine the effects of hepatic enzyme inducing drugs, such as anticonvulsants, on the pharmacokinetics.

• III. To determine the response rate of adult patients with recurrent glioma to BMS-247550 administered at the MTD.

• IV. To describe the toxicity associated with this regimen in adult patients with recurrent malignant gliomas.

SECONDARY OBJECTIVES:

• I. To determine the percent of patients with 6 month progression free survival, duration of progression free survival and survival associated with this therapy in adult patients with recurrent malignant gliomas.

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.#46;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.

Arms

Experimental: Group A [Anticonvulsants]

Phase I: Dose Escalation - 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. Pharmacological Study Phase 1

Experimental: Group B [No Anticonvulsants]

Phase I: Dose Escalation - 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. Pharmacological Study Phase 1

Experimental: Group C [MTD-Phase 2)

Maximum tolerated Dose (MTD-Phase 2) - subjects treated at dose determined by Group B Drug: ixabepilone Other Names: BMS-247550 epothilone B lactam Ixempra Given IV

Interventions

Drug: - ixabepilone

Given IV

Other: - pharmacological study

Correlative studies

Drug: - Anticonvulsant

Drugs that induce hepatic Metabolic enzymes