Clinical Drug Experience Knowledgebase

Criteria

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:

Recurrent/progressive disease at any time
Refractory disease (i.e. less than a partial response to frontline therapy)
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:

Measurable tumor on MRI or CT scan or X-ray
MIBG scan with positive uptake at minimum of one site
Bone marrow with tumor cells seen on routine morphology
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 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

Must not have received myelosuppressive chemotherapy and/or biologics within 3 weeks of entry onto this study (4 weeks if prior nitrosourea)
Patients must not have received radiation for a minimum of two weeks prior
Patients are eligible 12 weeks after autologous stem cell transplant
Minimum of six weeks is required following prior therapeutic doses of MIBG.
There is no limit on number of prior regimens
Must not have received any hematopoietic growth factors within 7 days/
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:

Hemoglobin greater than or equal to 8.0
ANC greater than or equal to 500 (7 days after last dose of growth factor)
Platelet count: greater than or equal to 50,000 at least one week since last platelet transfusion
Age-adjusted serum creatinine < 1.5 x normal for age
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
Total bilirubin less than or equal to 1.5 x normal for age
SGPT (ALT) and SGOT (AST) less than or equal to 3 x normal for age
Normal prothrombin time (PT) for age
Baseline hepatitis titers without evidence of acute/active hepatitis
Serum triglycerides < 300mg/dL fasting or on a random plasma test
Serum calcium < 11.6mg/dL
No hematuria and/or proteinuria greater than 1+ on urinalysis
Patients with a seizure disorder are study eligible if seizures are controlled on anticonvulsants
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

Exclusion Criteria:

Patients with CNS parenchymal or meningeal-based lesions that are present at study entry evaluation are NOT eligible
Pregnancy or breast feeding. Due to the potential teratogenic effects of retinoids, pregnant women are NOT eligible. Breast milk feeding by study patient is NOT allowed
Patients with history of organ and allogeneic stem cell transplantation
Patients with a known history of allergy to soy products
Patients with a known history of a severe allergy or sensitivity to wheat gluten
Patients requiring anti-arrhythmia cardiac medications are NOT eligible
Prior therapy with fenretinide, or fenretinide + ketoconazole, if DLT's were experienced
A known history of intolerance to ketoconazole
A known history of intolerance to vincristine
Patients on other essential medications for which an interaction with ketoconazole can be expected and for which dose reductions to other essential medications cannot be made in a manner adequate to ensure patient safety
Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
Active hepatitis
Baseline cardiac QTc interval > 450 msecs