A Phase I/II Trial of BMS-247550 for Treatment of Patients With Recurrent High-Grade Gliomas

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: delaviridine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir
  • Antifungals: itraconazole, ketoconazole, fluconazole (doses > 200mg/day), voriconazole
  • Antidepressants: nefazodone, fluovoxamine
  • 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