Phase II Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Children and Young Adults With Refractory Solid Tumors

Inclusion Criteria:

- 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)

- Refractory or recurrent disease with no known curative treatment options

- 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®

- 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 ofCYP3A4, including
any of the following:

- Clarithromycin

- Troleandomycin

- Erythromycin

- Ketoconazole

- Itraconazole

- Fluconazole (doses > 3mg/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