• Time to progression as measured by the product-limit method of Kaplan-Meier [ Designated as safety issue: No ]
  
• Progression-free survival at 6 months [ Designated as safety issue: No ]
  
• Response rates (complete response and partial response) [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  
• Correlate tumor burden and change in tumor burden by RECIST, WHO, and volumetric analysis [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the response rate to ixabepilone in various strata of recurrent solid malignant tumors of childhood and young adulthood, including all of the following:

  • Embryonal or alveolar rhabdomyosarcoma
  • Osteosarcoma
  • Ewing's sarcoma/peripheral neuroectodermal tumor
  • Synovial sarcoma or malignant peripheral nerve sheath tumor
  • Wilms' tumor
  • Neuroblastoma
• Determine the time to progression for each tumor stratum.
• Prospectively evaluate the feasibility and utility of automated volumetric tumor measurement in patients with measurable pulmonary metastases, and descriptively compare volumetric measurements to 1-dimensional (RECIST criteria) and 2-dimensional (WHO criteria) measurements.
• Define and describe the toxicities of ixabepilone.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (Ewing's sarcoma/ peripheral neuroectodermal tumor vs osteosarcoma vs alveolar or embryonal rhabdomyosarcoma vs Wilms' tumor vs neuroblastoma vs synovial sarcoma/malignant peripheral nerve sheath tumor).

Patients receive ixabepilone IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis (at original diagnosis or recurrence) of 1 of the following:

  • Embryonal or alveolar rhabdomyosarcoma
  • Osteosarcoma*
  • Ewing's sarcoma /peripheral neuroectodermal tumor*
  • Synovial sarcoma or malignant peripheral nerve sheath tumor*

  • Wilms' tumor*

    • Age ≤ 21 years at original diagnosis

  • Neuroblastoma

    • Age ≤ 21 years at original diagnosis

    • Clinically or radiographically measurable or evaluable (by iodine I 123 metaiodobenzoguanine sulfate [^123I-MIBG] or bone scan [evaluable tumors must be positive at ≥ 1 site])

      • If lesion was previously irradiated, a biopsy must be performed ≥ 6 weeks after completion of radiotherapy and viable neuroblastoma must be demonstrated
      • No elevated urinary catecholamines and/or bone marrow evidence of tumor with measurable disease clinically or by imaging modalities (CT scan, MRI, ^123I-MIBG, or bone scan) NOTE: *Measurable disease required; measurable disease is defined as lesions measured in ≥ 1 dimension by CT scan or MRI; ascites, pleural effusions, bone marrow disease, and lesions detectable only by bone scan not considered measurable disease
• Refractory or recurrent disease with no known curative treatment options

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100% (patients > 16 years of age) OR Lansky PS 50-100% (patients ≤ 16 years)
• Life expectancy ≥ 8 weeks
• No evidence of active graft-versus-host disease
• Absolute neutrophil count ≥ 1,500/mm³ (no growth factors)
• Platelet count ≥ 75,000/mm³ (transfusion independent)
• Not pregnant or nursing
• Fertile patients must agree to use effective contraception
• Negative pregnancy test
• Hemoglobin ≥ 8 g/dL (may receive RBC transfusions)
• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 2.5 times ULN

• No clinically significant unrelated systemic illness that would preclude study treatment, including any of the following:

  • Serious infections
  • Hepatic, renal, or other organ dysfunction
  • CNS toxicity ≤ grade 2
  • No pre-existing sensory or motor neuropathy ≥ grade 2
• Seizure disorder allowed provided it is well controlled by anticonvulsants
• No known prior severe hypersensitivity reaction to agents containing Cremophor EL®

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
• More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks if prior nitrosourea)
• At least 7 days since prior biologic agents
• At least 2 weeks since prior local palliative (small-port) radiotherapy
• At least 6 months since prior craniospinal radiotherapy OR radiotherapy to ≥ 50% of the pelvis
• At least 6 weeks since other prior substantial bone marrow radiotherapy
• At least 4 months since prior allogeneic stem cell transplant (SCT)
• At least 2 months since prior autologous SCT
• No prior taxane (paclitaxel, docetaxel) therapy
• More than 1 week since prior growth factor use (except epoetin alfa)

• More than 1 week since prior and no concurrent strong inhibitors of CYP3A4, including any of the following:

  • Clarithromycin
  • Troleandomycin
  • Erythromycin
  • Ketoconazole
  • Itraconazole
  • Fluconazole (doses > 3 mg/kg/day)
  • Voriconazole
  • Nefazodone
  • Fluvoxamine
  • Verapamil
  • Diltiazem
  • Amiodarone
  • Grapefruit juice

• More than 1 week since prior and no concurrent enzyme-inducing anticonvulsants, including any of the following:

  • Carbamazepine
  • Felbamate
  • Phenobarbital
  • Phenytoin
  • Primidone
  • Oxcarbazepine
• No concurrent aprepitant
• No concurrent Hypericum perforatum (St. John's wort)
• No concurrent sargramostim (GM-CSF) or interleukin-11
• No other concurrent chemotherapy or immunomodulating agents
• No concurrent radiotherapy
• Concurrent steroids allowed for pain or chemotherapy-associated nausea or vomiting