Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven't Responded to Therapy
Condition: 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
MeSH terms: Neoplasms; Leukemia; Sarcoma; Liver Neoplasms; Neuroblastoma; Neoplasms, Germ Cell and Embryonal; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): ixabepilone
Intervention type(s): Drug
Primary purpose: Treatment
Keywords: recurrent childhood rhabdomyosarcoma; childhood craniopharyngioma; recurrent neuroblastoma; recurrent childhood liver cancer; recurrent Wilms tumor and other childhood kidney tumors; childhood central nervous system germ cell tumor; recurrent osteosarcoma; unspecified childhood solid tumor, protocol specific; childhood germ cell tumor; recurrent childhood soft tissue sarcoma; childhood oligodendroglioma; childhood choroid plexus tumor; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood medulloblastoma; recurrent childhood visual pathway and hypothalamic glioma; previously treated childhood rhabdomyosarcoma; recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor; recurrent childhood ependymoma; childhood teratoma; childhood malignant testicular germ cell tumor; childhood malignant ovarian germ cell tumor; childhood extragonadal germ cell tumor; recurrent childhood malignant germ cell tumor; B-cell childhood acute lymphoblastic leukemia; childhood acute basophilic leukemia; childhood acute eosinophilic leukemia; childhood acute lymphoblastic leukemia; childhood acute myeloid leukemia in remission; childhood acute promyelocytic leukemia (M3); L1 childhood acute lymphoblastic leukemia; L2 childhood acute lymphoblastic leukemia; L3 childhood acute lymphoblastic leukemia; non-T, non-B, cALLa negative childhood acute lymphoblastic leukemia; non-T, non-B, cALLa positive childhood acute lymphoblastic leukemia; non-T, non-B, cALLa positive, pre-B childhood acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; TdT negative childhood acute lymphoblastic leukemia; TdT positive childhood acute lymphoblastic leukemia; chronic myelogenous leukemia, BCR-ABL1 positive; childhood chronic myelogenous leukemia