Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven't Responded to Therapy
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: This phase I trial is studying the side effects and best dose of ixabepilone in treating young patients with relapsed or refractory solid tumors or leukemia.
Brain and Central Nervous System Tumors
Childhood Germ Cell Tumor
Extragonadal Germ Cell Tumor
Unspecified Childhood Solid Tumor, Protocol Specific
|Study Design:||Primary Purpose: Treatment|
|Official Title:||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|
- Maximum tolerated dose and dose-limiting toxicity of ixabepilone [ Designated as safety issue: Yes ]
- Toxicity spectrum [ Designated as safety issue: Yes ]
- Plasma pharmacokinetics [ Designated as safety issue: No ]
- Pharmacodynamics [ Designated as safety issue: No ]
- Nerve growth factor levels before and after drug administration [ Designated as safety issue: No ]
- Objective tumor response [ Designated as safety issue: No ]
- Tubulin polymerization in PBMCs prior to the start of the infusion, just before the end of the infusion, 5 hours after the end of the infusion and before the start of the infusion on day 2 of the ixabepilone on course 1 [ Designated as safety issue: No ]
|Study Start Date:||November 2001|
|Study Completion Date:||April 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
- 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 patients.
- 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 leukemia cohort).
- Evaluate the plasma pharmacokinetics of in young patients with refractory or relapsed leukemia.
- 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 inhibitor.
- Evaluate the activity known drug transporters in drug-resistant leukemias in leukemic blasts.
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.
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010-2970|
|United States, Maryland|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office|
|Bethesda, Maryland, United States, 20892-1182|
|Study Chair:||AeRang Kim, MD||National Cancer Institute (NCI)|