Expanded Access Study of Fenretinide (4-HPR, NSC 374551) Lym-X-Sorb (LXS) Oral Powder Plus Ketoconazole in Patients With Recurrent or Resistant Neuroblastoma (IND#68,254)
Currently there is no known effective treatment for recurrent/resistant neuroblastoma. Fenretinide is an anticancer agent that may work differently than standard chemotherapy medicines. It may cause the buildup of wax-like substances in neuroblastoma cancer cells, called ceramides or other chemicals, called 'reactive oxygen species'. In laboratory studies it was found that if too much ceramide or reactive oxygen species build up in neuroblastoma cells, they may die. In addition, researchers are testing to see if a drug called ketoconazole, commonly used to treat fungus infections, can increase fenretinide levels in the body by interfering with the body's ability to break down fenretinide. This study is being done: 1) to allow patients with recurrent/refractory neuroblastoma patients who would otherwise not be able to access fenretinide/LXS oral powder for treatment to do so; 2) to further describe the side effects of fenretinide and ketoconazole when given by mouth for seven days every three weeks; 3) to determine if a patient's tumor gets smaller after treatment with fenretinide oral powder plus ketoconazole or fenretinide oral powder alone.
• diagnosis of neuroblastoma either by histologic verification and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
• must have high risk neuroblastoma with one of the following: 1) recurrent/progressive disease at any time, 2) refractory disease, 3) persistent disease after at least a partial response to frontline therapy, or 4) Second or greater complete remission after definitive disease progression.
• must have at least one of the following sites of disease: 1) measurable tumor on MRI, CT scan, or X-Ray; 2)MIBG scan with positive uptake in at least one site; 3) bone marrow with tumor cells seen on routine morphology.
• must have an ECOG performance status of 0, 1, or 2
• must have a life expectancy of greater than or equal to 8 weeks
• must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
• hemoglobin greater than or equal to 8.0 (may transfuse to achieve this level)
• ANC greater than or equal to 500 (must be at least 7 days after last dose of growth factor)
• platelet count greater than or equal to 50,000 (must be transfusion independent, defined as at least 1 week since last platelet transfusion)
• age-adjusted serum creatinine less than or equal to 1.5 times normal for age
• normal cardiac function documented by: ejection fraction (greater than or equal to 55%) documented by echocardiogram or radionuclide MUGA evaluation OR fractional shortening (greater than or equal to 27%) documented by echocardiogram AND EKG must demonstrate no abnormality severe enough to justify cardiac medications AND baseline QTc interval greater than or equal to 450 msecs
• total bilirubin less than or equal to 1.5 times normal for age
• ALT and AST less than or equal to 3 times normal for age (for this study, the upper limit of normal of ALT is defined as 45 U/L)
• normal prothrombin time (PT) for age
• baseline hepatitis titers without evidence of acute/active hepatitis. Patients will need to have a negative Hep B Surface Antigen (HBsAg), Hep B e Antigen (HBeAg), Anti-Hep B core Antibody IgM (Anti-HBc IgM), Anti-HAV IgM, and Anti-HCV IgM.
• Patients with CNS parenchymal or meningeal-based lesions are eligible. Patients with prior history of CNS irradiation are study eligible.
• Patients with a seizure disorder are eligible if seizures are controlled on anticonvulsants and if the specific anticonvulsant(s) is not contraindicated.
• Normal lung function as manifested by no dyspnea at rest and no oxygen requirement.
• Due to the potential teratogenic effects of retinoids, 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 per CTCAE v4
• 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 known genetic metabolic conditions, or other ongoing serious medical issues, must be approved by the Study Chair prior to registration.