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

Phase 2
21 Years
Not Enrolling
Recurrent Neuroblastoma

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Trial Information

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


Determine the response rate in pediatric patients with recurrent or resistant high-risk
neuroblastoma treated with fenretinide.

Determine the toxic effects of this drug in these patients. Determine the proportion of
patients with disease detected only by bone marrow immunocytology, who clear all evidence of
disease during treatment with this drug.

Determine minimal residual disease response by marrow and meta-iodobenzylguanidine (MIBG) I
123 scan in patients treated with this drug.

OUTLINE: Patients are stratified according to presence of measurable disease on CT scan/MRI
(yes vs no). A third stratum of patients with tumor cells in bone marrow by immunocytology
only is enrolled but is not evaluated for response.

Patients receive oral fenretinide 3 times daily (or 2 times daily if over 18 years of age)
on days 1-7. Treatment repeats every 3 weeks for up to 30 courses in the absence of disease
progression or unacceptable toxicity. Patients in stratum III who fail to achieve a complete
response after 8 courses of therapy are removed from study.

Patients are followed monthly until blood counts and visual acuity are stable or normalized
and then every 6 months for 2 years and annually for 3 years.

PROJECTED ACCRUAL: A total of 70 patients (25 each for strata I and II, 20 for stratum III)
will be accrued for this study within 1-2 years.

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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate

Outcome Description:

A responder is defined to be a patient who achieves a best overall response of complete response (CR), very good partial response (VGPR) or partial response (PR).

Outcome Time Frame:

Up to 8 courses of therapy

Safety Issue:


Principal Investigator

Judith Villablanca

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

December 1999

Completion Date:

Related Keywords:

  • Recurrent Neuroblastoma
  • Neuroblastoma



Children's Oncology Group Arcadia, California  91006-3776