Phase I Trial and Pharmacokinetic Study of BMS-247550 (NSC 710428, Ixabepilone), an Epothilone B Analog, in Pediatric Patients With Refractory Solid Tumors and Leukemias
- Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of
ixabepilone in young patients with refractory solid tumors (closed to accrual as of
10/4/2007) or relapsed or refractory leukemia.
- Determine the toxicity spectrum of this drug in these patients.
- Determine the plasma pharmacokinetics of this drug in these patients.
- Determine the pharmacodynamics of this drug in these patients.
- Assess the nerve growth factor levels, before and after the initiation of this drug, as
a potential surrogate marker for the development of peripheral neuropathy in these
- Determine the response of patients treated with this drug.
- Compare the tolerability, toxicity profile, MTD, DLT, pharmacokinetics, and
pharmacodynamics of this drug in young patients treated on this study vs adults with
solid tumors (closed to accrual as of 10/4/2007) treated on the ongoing Medicine
Branch, NCI, phase I study.
- Assess the safety and tolerability of ixabepilone at the solid tumor MTD (expanded
- Evaluate the plasma pharmacokinetics of in young patients with refractory or relapsed
- Evaluate the extent of tubulin polymerization in leukemic blasts at baseline after
treatment with ixabepilone ex-vivo.
- Compare the effects of tubulin polymerization in leukemic blasts with ixabepilone
versus paclitaxel ex-vivo with an without the presence of a potent P-glycoprotein
- Evaluate the activity known drug transporters in drug-resistant leukemias in leukemic
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive ixabepilone IV over 1 hour on days 1-5. Treatment repeats every 21 days in
the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 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 2 or more
of 6 patients experience dose-limiting toxicity. Intrapatient dose escalation to one dose
level above the enrollment dose level is allowed in patients who have stable or responding
disease or are experiencing other benefits from therapy (e.g., decrease in tumor-related
pain symptoms) and who have no grade 2 or greater non-hematologic toxicity and no grade 3 or
greater hematologic toxicity. Additional patients are treated at the MTD. Patients treated
at the MTD may not undergo intrapatient dose escalation.
PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 1-2 years.
Primary Purpose: Treatment
Maximum tolerated dose and dose-limiting toxicity of ixabepilone
AeRang Kim, MD
National Cancer Institute (NCI)
United States: Food and Drug Administration
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|