N2004-03: Intravenous Fenretinide in Treating Young Patients With Recurrent or Resistant Neuroblastoma

DISEASE CHARACTERISTICS:

   - Diagnosis of neuroblastoma either by histological confirmation and/or demonstration of
   tumor cells in the bone marrow with increased urinary catecholamines

      - Differentiating ganglioneuroblastoma allowed

         - No histological evidence only of ganglioneuroma by tumor biopsy or bone
         marrow biopsy

   - High-risk disease meeting at least one of the following criteria:

      - Recurrent/progressive disease at any time

      - Refractory disease (i.e., less than a partial response to front-line therapy that
      included ≥ 4 courses of chemotherapy)

      - Persistent disease after at least a partial response to front-line therapy (i.e.,
      still has residual disease by MIBG, CT/MRI, or bone marrow biopsy)

         - Biopsy of at least one residual site demonstrating viable neuroblastoma
         required (tumor by bone marrow morphology is considered adequate
         documentation of disease)

   - Measurable disease meeting at least one of the following criteria:

      - Measurable tumor on MRI or CT scan, defined as at least one unidimensionally
      measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan

         - For patients with persistent disease, a biopsy* of bone marrow or bone or
         soft tissue site must have demonstrated viable neuroblastoma

      - MIBG scan with positive uptake at a minimum of one site

         - For patients with persistent disease, a biopsy* of a MIBG positive site must
         have demonstrated viable neuroblastoma

      - Bone marrow with tumor cells seen on routine morphology (not by NSE staining
      only) of bilateral aspirate and/or biopsy of one bone marrow sample NOTE: *If the
      lesion was irradiated, the biopsy must have been done at least 4 weeks after
      completion of radiotherapy

   - No CNS parenchymal or meningeal-based lesions

      - Skull-based tumor lesions with or without intracranial extension are allowed
      provided there are no neurologic signs or symptoms or hydrocephalus related to
      the lesion

      - Patients with a history of complete surgical resection of CNS lesions are
      eligible provided there is no evidence of CNS lesions by MRI or CT scan at study
      entry

      - Patients with a history of CNS lesions must be off corticosteroid therapy for CNS
      lesions for ≥ 4 weeks

PATIENT CHARACTERISTICS:

   - Performance status 0-2

   - Life expectancy ≥ 2 months

   - ANC ≥ 500/mm³

   - Platelet count ≥ 50,000/mm³ (transfusion independent)

   - Hemoglobin ≥ 8.0 g/dL (transfusion independent)

   - Serum creatinine ≤ 1.5 times normal for age

   - Total bilirubin ≤ 1.5 times normal for age

   - ALT and AST ≤ 3 times normal for age

   - Serum triglycerides < 300 mg/dL

   - Serum calcium < 11.6 mg/dL

   - Lipase normal for age

   - PT/PTT ≤ 1.5 times upper limit of normal for age (without fresh frozen plasma support;
   vitamin K allowed)

   - Not pregnant or nursing

   - Negative pregnancy test

   - Fertile patients must use effective contraception prior to, during, and for 2 months
   after completion of study treatment

   - LVEF ≥ 55% by ECHO or MUGA scan OR fractional shortening ≥ 27% by ECHO

   - No EKG abnormality

   - No dyspnea at rest or requirement for oxygen

   - No hematuria and/or proteinuria > 1+ on urinalysis

   - No known history of allergy to egg products

   - No known history of allergy to soy bean oil

   - No skin toxicity > grade 1 per CTCAE v3

   - Seizure disorder allowed if seizures are controlled on anticonvulsants and the
   anticonvulsant(s) is not contraindicated

   - Known genetic, metabolic, or psychiatric conditions, or other ongoing serious medical
   issues must be approved by the study chair prior to study registration

PRIOR CONCURRENT THERAPY:

   - Recovered from all prior chemotherapy, immunotherapy, or radiotherapy

   - More than 3 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas)
   and/or biologic therapy without stem cell support

   - More than 7 days since prior hematopoietic growth factors

   - No prior radiotherapy to the only site of measurable disease unless there has been
   subsequent disease progression at that site or a biopsy of that site showed viable
   neuroblastoma ≥ 4 weeks after completion of radiotherapy

   - Prior CNS irradiation allowed

   - At least 2 weeks since prior small field (focal) radiotherapy

   - At least 6 weeks since prior large field radiotherapy (i.e., total-body irradiation,
   craniospinal radiotherapy, whole abdominal or total lung radiotherapy, or radiotherapy
   to > 50% of marrow space)

   - At least 56 days since prior myeloablative autologous stem cell transplantation

   - At least 4 weeks since prior myelosuppressive therapy with stem cell support

   - At least 6 weeks since prior MIBG therapy

   - Prior oral fenretinide therapy allowed

   - At least 3 weeks since prior retinoid therapies

   - No prior organ transplantation

   - No prior myeloablative allogeneic stem cell transplantation unless stem cells were
   from an identical twin sibling

   - No concurrent systemic corticosteroids, including corticosteroids for emesis control

      - Concurrent inhaled corticosteroids for asthma control or steroids for metabolic
      deficiency states allowed

   - Concurrent palliative radiotherapy allowed provided the irradiated sites will not be
   used to measure response

   - No concurrent parenteral intralipids

   - No other concurrent chemotherapy or immunomodulating agents

   - No concurrent drugs suspected of causing pseudotumor cerebri, including tetracycline,
   nalidixic acid, nitrofurantoin, phenytoin, sulfonamides, lithium, or amiodarone

   - No concurrent vitamin A, C, or E supplements (except as part of routine total
   parenteral nutrition [TPN] supplements or as part of a single daily standard dose of
   oral multivitamin supplement)

   - No concurrent medications that may potentially act as modulators of intracellular
   ceramide levels or ceramide cytotoxicity, sphingolipid transport, or p-glycoprotein
   (MDR1) or MDR1 drug/lipid transporters, including cyclosporine or analogue, verapamil,
   tamoxifen or analogue, ketoconazole, chlorpromazine, mifepristone (RU486),
   indomethacin, or sulfinpyrazone

   - No other concurrent anticancer agents

   - No concurrent herbal supplements or other alternative therapy medications

   - No concurrent anti-arrhythmia or inotropic cardiac medications