Fenretinide Lym-X-Sorb + Ketoconazole + Vincristine for Recurrent or Resistant Neuroblastoma

Inclusion Criteria

• •Diagnosed with neuroblastoma either by histological verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines
• •Patients must have high-risk neuroblastoma with at least ONE of the following:
• •1. Recurrent/progressive disease at any time
• •2. Refractory disease (i.e. less than a partial response to frontline therapy)
• •3. Persistent disease after at least a partial response to frontline therapy (i.e. patient has had at least a partial response to frontline therapy but still has residual disease by MIBG, CT/MRI, or bone marrow)
• •Patients must have at least ONE of the following sites of disease:
• •1. Measurable tumor on MRI or CT scan or X-ray
• •2. MIBG scan with positive uptake at minimum of one site
• •3. Bone marrow with tumor cells seen on routine morphology
• •Patients must have a performance status of 0, 1 or 2 (Appendix I). Patients who are unable to walk because of paralysis or tumor pain, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• •Patients must have a life expectancy of greater than or equal to 8 weeks
• •Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• •1. Must not have received myelosuppressive chemotherapy and/or biologics within 3 weeks of entry onto this study (4 weeks if prior nitrosourea)
• •2. Patients must not have received radiation for a minimum of two weeks prior
• •3. Patients are eligible 12 weeks after autologous stem cell transplant
• •4. Minimum of six weeks is required following prior therapeutic doses of MIBG.
• •5. There is no limit on number of prior regimens
• •6. Must not have received any hematopoietic growth factors within 7 days/
• •7. Prior therapy with fenretinide and/or fenretinide + ketoconazole is allowed if no DLT's were experienced. Prior therapy with other retinoids
• •Patients must NOT receive other anti-cancer agents while on study
• •Palliative radiation is allowed to sites that will not be used to measure response during this study
• •All patients must have adequate organ function defined as:
• •1. Hemoglobin greater than or equal to 8.0
• •2. ANC greater than or equal to 500 (7 days after last dose of growth factor)
• •3. Platelet count: greater than or equal to 50,000 at least one week since last platelet transfusion
• •4. Age-adjusted serum creatinine \< 1.5 x normal for age
• •5. Patient must have normal cardiac function documented by ejection fraction (\> 55%) documented by echocardiogram or radionuclide MUGA evaluation or fractional shortening ( \> 27%) documented by echocardiogram and EKG must demonstrate no abnormality severe enough to justify cardiac medications and baseline QTc interval less than or equal to 450 msecs
• •6. Total bilirubin less than or equal to 1.5 x normal for age
• •7. SGPT (ALT) and SGOT (AST) less than or equal to 3 x normal for age
• •8. Normal prothrombin time (PT) for age
• •9. Baseline hepatitis titers without evidence of acute/active hepatitis
• •10. Serum triglycerides \< 300mg/dL fasting or on a random plasma test
• •11. Serum calcium \< 11.6mg/dL
• •12. No hematuria and/or proteinuria greater than 1+ on urinalysis
• •Normal lung function as manifested by no dyspnea at rest and no oxygen requirement
• •Negative serum beta-HCG in females, and use of effective contraception in males and females of child-bearing potential, is required
• •Skin toxicity no greater than grade 1
• •Patients with known genetic metabolic conditions, or other ongoing serious medical issues, must be approved by the Study Chair prior to registration