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