Randomized Efficacy Study of TPI 287 to Treat Primary Refractory or Early Relapsed Neuroblastoma

Inclusion Criteria

• •Subjects must have histologically proven Neuroblastoma and confirmation of primary refractory or recurrent disease with histologic confirmation at diagnosis or at the time of recurrence/progression. Subjects must have primary refractory or have early relapse disease (early relapse disease is defined as having received ≤ one or two relapse therapies).
• •Subjects must be age \>12 months and diagnosed before the age of 21 years
• •Measurable disease, including at least one of the following:
• •Measurable tumor \>10 mm by CT or MRI Positive bone marrow biopsy/aspirate Positive MIBG
• •Current disease state must be one for which there is currently no known curative therapy
• •Lansky Play Score or Karnofsky scale must be more than 30
• •Subjects without bone marrow metastases must have an ANC \> 750/μl and platelet count \>50,000/μl
• •Adequate Renal Function Defined As Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or
• •A serum creatinine based on age/gender table
• •Adequate liver function must be demonstrated, defined as:
• •Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age SGPT (ALT) \< 10 x upper limit of normal (ULN) for age SGOT (AST) \< 10x upper limit of normal (ULN) for age
• •No other significant organ toxicity defined as \>Grade 2 by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE V4.0- http://ctep.cancer.gov/forms/CTCAEv4.pdf)
• •A negative urine pregnancy test is required for female participants of child bearing potential (≥13 years of age or after onset of menses)
• •Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.
• •Informed Consent: All subjects and/or legal guardians must sign written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
• •Subjects may have received microtubulin inhibitors during previous therapies.
• •Subjects may have received any number of prior biological therapies.