Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven't Responded to Therapy

Phase 1

Completed

• Conditions: Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Leukemia; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

• Registration Number: NCT00030108
• Lead Sponsor: National Institutes of Health Clinical Center (CC)

Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

* 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.

Secondary

* 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.

Study Timeline

• Study Start: 2001-11
• Study First Submitted: 2002-01-30
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Primary Completion: 2010-03
• Study Completion: 2010-04
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-14
• Last Update Posted: 2012-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose and dose-limiting toxicity of ixabepilone
Toxicity spectrum
Plasma pharmacokinetics
Pharmacodynamics
Nerve growth factor levels before and after drug administration

Secondary Outcome Measures

Name	Time	Method
Objective tumor response
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

Trial Locations

Locations (2)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office; 🇺🇸 Bethesda, Maryland, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States