SPOC-2013-001, Phase I Study of Fenretinide (4-HPR, NSC 374551) Lym-X-Sorb(LXS) Oral Powder Plus Ketoconazole Plus Vincristine in Patients with Recurrent or Resistant Neuroblastoma (IND #: 68,254)

1. Patients must be < 30 years of age inclusive when registered on study. 2. Patients must have a diagnosis of neuroblastoma either by histological verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines. 3. Patients must have high-risk neuroblastoma with at least ONE of the following: a. Recurrent/progressive disease at any time. b. Refractory disease (i.e. less than a partial response to frontline therapy). No biopsy is required for eligibility for study. c. 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 in this category are REQUIRED to have a biopsy of at least one residual site demonstrating viable neuroblastoma. 4. Patients must have at least ONE of the following sites of disease: a. Measurable tumor on MRI or CT scan or X-ray. Measurable is defined as minimum 20 mm in at least one dimension; for spiral CT defined as minimum of 10 mm in at least one dimension. For patients with persistent disease, a biopsy of bone and/or soft tissue site seen on CT/MRI must have been done to demonstrate viable neuroblastoma. If lesion was radiated, biopsy must be done at least 2 weeks after radiation completed. b. MIBG scan with positive uptake at minimum of one site. For patients with persistent disease, a biopsy of an MIBG positive site must have been done to demonstrate viable neuroblastoma. If lesion was radiated, biopsy must be done at least 2 weeks after radiation completed. c. Bone marrow with tumor cells seen on routine morphology (not by NSE staining only) of bilateral aspirate and/or biopsy on one bone marrow sample. 5. Patients with CNS parenchymal or meningeal-based lesions that are present at study entry evaluation are NOT eligible. This is because CNS symptoms caused by CNS tumor may be wrongly attributed to drug toxicity. Skull-based tumor lesions with or without intracranial extension are eligible so long as there are no neurological signs or symptoms or hydrocephalus related to the lesions. Patients with a history of complete surgical resection of CNS lesions are eligible if there is no evidence of CNS lesions (MRI or CT required) at study entry evaluation and if other entry criteria are met. Patients with prior history of CNS irradiation are study eligible. Patients with a history of CNS lesions must be off of corticosteroid therapy for CNS lesions for four weeks to be study eligible. 6. Patients must have a performance status of 0, 1 or 2. 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 >/= 8 weeks. 7. Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. a. Myelosuppressive chemotherapy and/or biologics: Must not have received within 3 weeks of entry onto this study (4 weeks if prior nitrosourea). b. XRT: Patients must not have received radiation for a minimum of two weeks prior to study entry at the site of any lesion that was biopsied to document study eligibility or if radiation was given to only site of measurable disease. A minimum of six weeks is required following prior large field radiation therapy (i.e. TBI, craniospinal therapy, whole abdomen, total lung, > 50% marrow space). c. Stem Cell Transplant (SCT) or support: Patients are eligible 12 weeks after autologous stem cell transplant (i.e., autologous stem cell rescue after a regimen with myeloablative intent) if hematological and all other criteria are met. Patients that receive autologous stem cell [?]support[Single Quote] after a myelosuppressive, but not intentionally myeloablative, regimen are eligible when hematological and all other criteria are met. Patients status post allogeneic stem cell transplant are NOT eligible. d. Prior MIBG therapy: A minimum of six weeks is required following prior therapeutic doses of MIBG. e. Study specific limitations on prior therapy: There is no limit on number of prior regimens. f. Growth factor(s): Must not have received any hematopoietic growth factors within 7 days of study entry. g. Organ Transplant: Patients may NOT be the recipient of an organ transplant. h. Study specific limitations on prior therapy: Prior therapy with fenretinide and/or fenretinide + ketoconazole is allowed if no DLT[Single Quote]s were experienced. Prior therapy with other retinoids (ex: 13-cis-retinoic acid) is allowed. 8. Organ Function Requirements All patients must have adequate organ function defined as: Hematologic Function: As it is not known if fenretinide at doses potentially achievable by the present 4-HPR/LXS oral powder formulation causes hematopoietic toxicity, the following criteria must be met by all patients regardless of bone marrow involvement by tumor: a. Hemoglobin >/= 8.0. May transfuse to achieve this level. b. ANC: >/= 500. Must be at least 7 days after last dose of growth factor. c. Platelet count: >= 25,000. Must be transfusion independent, defined as at least one week since last platelet transfusion. Renal Function: Age-adjusted serum creatinine < 1.5 x normal for age (see below): Age Maximum Serum Creatinine (mg/dL) 5 and 10 and 15 years: 1.5 Cardiac Function: Patient must have normal cardiac function documented by: a) ejection fraction (>/= 55%) documented by echocardiogram or radionuclide MUGA evaluation OR b) fractional shortening (>/= 27%) documented by echocardiogram. AND c) EKG must demonstrate no abnormality severe enough to justify cardiac medications. d) Baseline QTc interval