A Phase II Study of Fenretinide (NSC # 374551, IND #40294) in Children With Recurrent/Resistant High Risk Neuroblastoma

Inclusion Criteria:

- Diagnosis of recurrent or resistant/refractory high-risk neuroblastoma by one or both
of the following:

- Histological confirmation

- Demonstration of tumor cells in bone marrow with increased urinary
catecholamines

- Stratum I:

- At least 1 unidimensionally measurable lesion*

- At least 20 mm by MRI and/or CT scan OR at least 10 mm by spiral CT scan

- Stratum II: Meets one or both of the following criteria:

- At least 1 site with positive uptake on meta-iodobenzylguanidine (MIBG) I 123
scan

- Tumor in bilateral bone marrow aspirate/biopsy by routine morphology (no NSE
staining only)

- Stratum III:

- At least 5 tumor cells/10^6 mononuclear cells in the bone marrow by
immunocytology only (on 2 successive bone marrows performed from 1 day to 4
weeks apart)

- Patients in first response (i.e., patients with persistent tumor at end of frontline
therapy, but who have never had disease relapse or progression) must have
histological* or morphological (by bone marrow) confirmation** of viable tumor on CT
scan, MRI, or MIBG scan after completion of myeloablative therapy (for strata I and
II)

- No catecholamine elevation only

- Performance status - 0-2

- At least 2 months

- Hemoglobin greater than 7.5 g/dL (transfusion allowed)

- Bilirubin no greater than 1.5 times normal

- SGPT and SGOT less than 2.5 times normal

- Creatinine normal for age

- No hematuria or proteinuria greater than 1+ on urinalysis

- Calcium less than 11.6 mg/dL

- Triglycerides less than 300 mg/dL

- Not pregnant

- Negative pregnancy test

- Fertile patients must use effective contraception

- No seizure disorders unless on anticonvulsants and well controlled

- No skin toxicity greater than grade 1

- Must be able to consume entire intact study capsule in the dosage prescribed for body
surface area

- Recovered from prior immunotherapy

- At least 7 days since prior anticancer biologic therapy

- At least 2 days since prior growth factors

- Prior autologous stem cell transplantation allowed

- No prior allogeneic stem cell transplantation

- No concurrent immunomodulating agents

- At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas)
and recovered

- No concurrent anticancer chemotherapy

- No concurrent steroids

- Recovered from prior radiotherapy

- At least 4 weeks since prior radiotherapy to target lesion

- Prior radiotherapy to non target lesions allowed

- No concurrent radiotherapy to sole measurable lesion for symptom relief

- Concurrent palliative radiotherapy to non target or localized painful lesions allowed

- Prior tretinoin or isotretinoin allowed

- At least 2 weeks since other prior retinoids

- No prior fenretinide

- No concurrent supplemental oral or IV vitamin A, ascorbic acid, or vitamin E (except
if contained in routine total parenteral nutrition [TPN] vitamin supplements)

- No concurrent drugs suspected of causing pseudotumor cerebri (e.g., tetracycline,
nalidixic acid, nitrofurantoin, phenytoin, sulfonamides, lithium, amiodarone, or
vitamin A [except as part of routine TPN supplements])

- No other concurrent anticancer agents